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  • 2000-2004
  • 1995-1999
  • 1990-1994  (2,314)
  • 1920-1924
  • 1993  (2,314)
  • Life and Medical Sciences  (2,230)
  • breast cancer
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  • 2000-2004
  • 1995-1999
  • 1990-1994  (2,314)
  • 1920-1924
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  • 1
    Electronic Resource
    Electronic Resource
    A clinicopathological analysis of breast cancer in patients with a family history (1993)
    Springer
    Surgery today 23 (1993), S. 849-854 
    Details
    ISSN: 1436-2813
    Keywords: family history ; breast cancer ; c-erbB-2 ; prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was conducted to investigate the clinical and pathological characteristics of breast cancer in patients with a family history (FH). Among 4,481 primary breast cancer patients, 394 (8.8%) had families which included two or more breast cancer patients within three generations (FH(+) group). This group was compared with the remaining 3,969 patients (FH(−) group) with the following results: (1) The tumor diameter in the FH(+) group was slightly less than that in the FH(−) group [not significant (NS)], with fewer lymph node metastases (P〈0.05); (2) the positive rates for the estrogen receptor were 52% (138/266) and 49% (1,216/2,481), respectively (NS); (3) expression of the c-erbB-2 protein was observed in 14 out of 40 (35%) and 32 out of 100 cases (32%), respectively (NS); (4) the relative risk of bilateral occurrence in the FH(+) group was 1.4, with a 95% confidence interval of 0.9–2.4; (5) the 15-year survival rate was 72% and 60%, respectively, suggesting a better prognosis for the FH(+) group (P〈0.01); and (6) multivariate analysis showed that the contribution of FH to postoperative survival was marginal (P=0.07). Factors related to the hormonal environment such as age at menarche (P=0.08) and age at menopause (P=0.08) made a greater but non-significant contribution to the prognosis of the FH(+) group than to that of the FH(−) group. However, further genetic and molecular biological analyses of familial breast cancer are needed in order to clarify the mechanisms of cancer accumulation within families.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311360
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  • 2
    Electronic Resource
    Electronic Resource
    Immunohistochemical overexpression of C-erbB-2 in the prognosis of breast cancer (1993)
    Springer
    Surgery today 23 (1993), S. 885-890 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; c-erbB-2 overexpression ; DNA ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical c-erbB-2 protein overexpression was detected in 34 of 124 (27.4%) paraffin-embedded breast cancer specimens. Although no difference was seen between the c-erbB-2 positive and negative groups in 5-year disease-free survival, 5-year overall survival was significantly less favorable in the c-erbB-2 positive group. Furthermore, patients graded as having positive c-erbB-2 staining and aneuploid DNA showed significantly poorer survival than those in other categories. The significant prognostic factors, determined by a multivariate analysis, were nodal status and c-erbB-2 overexpression. Our findings therefore suggest that c-erbB-2 expression is a prognostic factor in breast cancer and that it could be useful in the determination of postoperative adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311367
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  • 3
    Electronic Resource
    Electronic Resource
    Primary scirrhous carcinoma of the nipple with symptoms simulating Paget's disease: Report of a case (1993)
    Springer
    Surgery today 23 (1993), S. 356-359 
    Details
    ISSN: 1436-2813
    Keywords: scirrhous carcinoma of the nipple ; breast cancer ; aspiration biopsy cytology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein an extremely rare case of primary scirrhous carcinoma of the nipple, being of particular interest in that the patient presented with symptoms very similar to those of Paget's disease. The carcinoma cells were detected by aspiration biopsy cytology rather than by touch smear, although both were performed to differentiate this lesion from Paget's disease and other diseases of the nipple. Thus, we recommend that both touch smear and aspiration biopsy cytology should be performed for all patients presenting with symptoms such as those observed in this case to rule out the possibility of scirrhous carcinoma of the nipple or Paget's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309055
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  • 4
    Electronic Resource
    Electronic Resource
    A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer (1993)
    Springer
    Surgery today 23 (1993), S. 573-579 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; axillary lymph node metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311903
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  • 5
    Electronic Resource
    Electronic Resource
    Primary squamous cell carcinoma of the breast after cured Hodgkin's disease (1993)
    Springer
    Surgery today 23 (1993), S. 81-84 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; squamous cell carcinoma ; Hodgkin's disease ; double cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309006
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  • 6
    Electronic Resource
    Electronic Resource
    Breast cancer in a male patient with prolactinoma (1993)
    Springer
    Surgery today 23 (1993), S. 251-255 
    Details
    ISSN: 1436-2813
    Keywords: prolactinoma ; hyperprolactinemia ; breast cancer ; male breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 68-year-old manw as diagnosed as having left primary breast cancer. Systemic bone roentgenography showed no evident metastasis, however, skull roentgenography revealed ballooning of the sella turcica, suggesting a pituitary tumor, which was subsequently confirmed by computed tumography. Because there was a high serum prolactin level, the pituitary tumor was diagnosed as a prolactinoma. A modified radical mastectomy was performed for the breast cancer, and bromocriptine therapy given for the prolactinoma. Prolactin is known to initiate and promote breast cancer in mice and rats but little is known about its role in human breast cancer. If hyperprolactinemia plays an important role in the tumorigenesis of human breast cancer as it does in mice and rats, the incidence of breast cancer in patients with hyperprolactinemia may be high. To our knowledge, however, only four such cases have been reported. The present rare case of male breast cancer with prolactinoma is discussed with reference to the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309236
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  • 7
    Electronic Resource
    Electronic Resource
    Procollagen type III N-peptide and type IV collagen 7S-domain in the sera of breast cancer patients (1993)
    Springer
    Surgery today 23 (1993), S. 682-686 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; tumor marker ; procollagen type III N-peptide ; type IV collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the usefulness of serum levels of procollagen type III N-peptide (P III P) and the type IV collagen, 7S-domain, (IV-C) as markers of recurrent and metastatic breast cancer. Serum P III P and IV-C levels were found to be significantly higher in patients who showed postoperative recurrence, with 76.9% of P III P-positive cancer bearing patients and 68.0% of IV-C-positive cancer bearing patients having metastases in the bone and/or liver. Furthermore, 66.7% of all patients with metastases in the bone and/or liver were P III P-positive and 75.6% were IV-C-positive. Patients with liver metastases were either P III P- or IV-C-positive, and the levels were higher than those in patients with bone metastases. Thus, a positive correlation of serum P III P and IV-C levels was observed. These findings suggest that both serum P III P and IV-C levels are useful markers of recurrent and metastatic breast cancer, especially of disease in the bone and/or liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311705
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  • 8
    Electronic Resource
    Electronic Resource
    The quality of mass screening for breast cancer by physical examination (1993)
    Springer
    Surgery today 23 (1993), S. 200-204 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; mass screening ; physical examination ; sensitivity ; specificity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mass screening for breast cancer using physical examination alone has been carried out since 1983 in Zentsuji, Kagawa Prefecture, Japan. Over a 7-year period, breast cancer was detected in 11 of a total 8,271 examinees, the detection rate being high at 0.13%. The detected cases included a few early-staged breast cancers, suggesting that mass screenings are of slight efficacy. Seven cases of interval cancer were found by breast self-examination after the mass screenings, supporting the value of breast self-examination. A relatively large number of interval breast cancers was detected in 1985 and 1986, when the rates of required further examination remained under 1%. The sensitivity and specificity of this screening were 61.1% and 94.5%, respectively, indicating a low sensitivity. These results suggest that the qualitative diagnoses made from the first screening by physical examination alone were often revealed to be false negatives. Therefore, the existing diagnosis should be employed in the first screenings. It is recommended that mammography be introduced to detect breast tumors which are nonpalpable or undetectable by physical examination alone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309228
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  • 9
    Electronic Resource
    Electronic Resource
    A comparison of breast cancers detected by mass screening and those found in out-patient clinics (1993)
    Springer
    Surgery today 23 (1993), S. 325-330 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; mass screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the results of a mass screening study on breast cancer detection by physical examination alone conducted in Ishikawa Prefecture from 1978 to 1990. The number of cases of breast cancer detected by mass screening was then compared with that found in out-patient clinics during the same period. Breast cancer was detected in 88 of 152,969 women by mass screening, the detection rate being 0.06% for the total study: 0.08% at the initial screening and 0.04% at periodic screenings. Early stage breast cancer was more frequently detected during periodic screenings than at the initial screening or in out-patient clinics. Moreover, although the initial screenings may have identified patients with breast cancer at more advanced stages, the survival was not significantly different. The results of this series led us to conclude that mass screening by physical examination alone may have no impact on the mortality rate of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00309050
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  • 10
    Electronic Resource
    Electronic Resource
    A comparison between ultrasonography and mammography, computed tomography and digital subtraction angiography for the detection of breast cancers (1993)
    Springer
    Surgery today 23 (1993), S. 704-710 
    Details
    ISSN: 1436-2813
    Keywords: ultrasound ; mammography ; computed tomography ; digital subtraction angiography ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ultrasound (US) was compared with mammography (MMG), computed tomography (CT), and digital subtraction angiography (DSA) in its effectiveness to detect breast cancer masses and metastatic axillary nodes. Forty-seven breast cancer patients who all underwent MMG, US, CT, and DSA preoperatively in our institution between 1986 and 1990 were studied. US was able to detect tumors in all cases regardless of tumor size, whereas DSA detected T1-size tumors and MMG detected T2-size tumors in 40% and 64.7% of cases, respectively, being specifically inferior to US. It was found that MMG was least likely to detect papillotubular carcinoma, although microcalcification alone without a tumor mass on MMG improved detectability from 46.2% to 76.9%, according to the histological type. CT was found to be most sensitive to axillary node metastases (81.8%), followed by US (72.7%), but DSA was significantly unfavorable (42.9%). Thus, we concluded that US was superior to MMG, CT, and DSA for detecting breast cancer masses, but that CT was more advantageous than US, while DSA was of little value for evaluating axillary nodal status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311709
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  • 11
    Electronic Resource
    Electronic Resource
    The family's functioning with newly diagnosed breast cancer in the mother: The development of an explanatory model (1993)
    Springer
    Journal of behavioral medicine 16 (1993), S. 351-370 
    Details
    ISSN: 1573-3521
    Keywords: family functioning ; breast cancer ; model development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Despite the high rates of breast cancer in the child-rearing mother, there is extremely limited research on the effects of the illness on the children, marriage, and parent-child relationship. The current study tested an explanatory model of family functioning with breast cancer based on data obtained from standardized questionnaires from 80 diagnosed mothers and partners with young school-age children. Path analysis results for data obtained from both the mothers and the partners revealed a similar pattern. More frequently experienced illness demands were associated with higher levels of parental depressed mood which negatively affected the marriage. When the marriage was less well adjusted, it negatively affected the family's coping behavior. Household functioning was positively affected by heightened coping activity and by higher levels of marital adjustment. Children functioned better when the non-ill parent more frequently interacted with them and their families coped more frequently with their problems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00844777
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  • 12
    Electronic Resource
    Electronic Resource
    Phase II trial of doxorubicin and trifluoperazine in metastatic breast cancer (1993)
    Springer
    Investigational new drugs 11 (1993), S. 75-79 
    Details
    ISSN: 1573-0646
    Keywords: doxorubicin ; trifluoperazine ; breast cancer ; drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting in an increased rate of complete response or a prolongation in response duration. Twenty patients with metastatic breast cancer were treated every 3 weeks with TFP 5 mg by mouth every 6 hours on days 0–5 and doxorubicin 60 mg/m2/96 hr on days 1–4 by continuous intravenous infusion. The first 5 patients were treated with TFP 15 mg by mouth every 6 hours, but the dose was reduced to 5 mg every 6 hours when grade 3–4 extrapyramidal toxicity was noted in 3 of the first 5 patients. Thereafter, neurologic toxicity was grade 0–2. No complete and 9 partial responses were produced in 20 patients (45%). The median response duration was 17 weeks (range 7–112). The combination of trifluoperazine and doxorubicin did not seem to produce a response rate or duration markedly different than that expected for doxorubicin alone in patients with metastatic breast cancer. Alternative trial designs may be necessary in future clinical trials investigating the inhibition of acquisition of drug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873916
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  • 13
    Electronic Resource
    Electronic Resource
    Brain metastases in breast cancer; natural history, prognostic factors and outcome (1993)
    Springer
    Journal of neuro-oncology 15 (1993), S. 165-174 
    Details
    ISSN: 1573-7373
    Keywords: breast cancer ; adjuvant chemotherapy ; brain metastasis ; tumor characteristics ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One hundred and thirty seven breast cancer patients with CT scan documented brain metastasis (BM) were reviewed. Occurrence of brain as first site of relapse was associated with adjuvant systemic therapy of the primary tumor. Multivariate analysis showed significantly longer survival in patients without manifest systemic disease, in patients with a solitary BM, in those with neurologic symptoms present for more than 4 weeks prior to diagnosis, and in those treated with chemotherapy after diagnosis. When controlling for prognostic factors no significant difference in survival was found between surgery and radiotherapy (RT) as treatment of a solitary lesion. Tumor size, tumor necrosis and mass effect had no demonstrable influence on survival. Overall median survival was 16 weeks and 19% survived one year. Neurologic disease was the cause of death or a major contributing factor to it in 68% of the patients, indicating the need for improvement of the treatment of BM itself. These results warrant further studies on the value of surgery, RT and chemotherapy in solitary as well as multiple BM from breast carcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053937
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  • 14
    Electronic Resource
    Electronic Resource
    Sexuality for women with cancer: Assessment, theory, and treatment (1993)
    Springer
    Sexuality and disability 11 (1993), S. 7-37 
    Details
    ISSN: 1573-6717
    Keywords: Sexuality ; cancer ; breast cancer ; gynecologic cancer ; schema ; sexual dysfunction ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Women with cancer are at risk for sexual difficulties and dysfunction(s) following treatment. Common malignancies (breast, colo/rectal, lung, gynecologic and hemotologic) are described and a brief review of sexual outcomes is provided. The domains for assessment are presented, including sexual behavior, the sexual response cycle and corresponding dysfunctions, and sexual schema (i.e. sexual self concept). A process model for the occurance and maintenance of sexual difficulties is proposed, and clinical treatment strategies are detailed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01102307
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  • 15
    Electronic Resource
    Electronic Resource
    Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer (1993)
    Springer
    Breast cancer research and treatment 24 (1993), S. 195-208 
    Details
    ISSN: 1573-7217
    Keywords: protease ; inhibitor ; urokinase ; uPA ; PAI-1 ; cathepsin D ; prognosis ; breast cancer ; axillary node-negative patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. The serine protease urokinase-type plasminogen activator (uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzyme-linked immunoassays (ELISA) to test for uPA antigen and its inhibitor PAI-1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study. The relation of these data to known prognostic factors and to other variables such as DNA analysis and cathepsin D was studied. Disease-free and overall survival were analyzed according to Cox's proportional hazard model. The major new finding is that breast cancer patients with either high uPA (〉2.97 ng/mg protein) or high content of the uPA inhibitor PAI-1 (〉2.18 ng/mg protein) in their primary tumors have an increased risk of relapse and death. Multivariate analyses revealed uPA to be an independent and strong prognostic factor. The impact of uPA is as high as that of the lymph node status. In node-negative patients the impact of uPA is closely followed by that of PAI-1. Since uPA and PAI-1 are independent prognostic factors, the node-negative patients could be subdivided further by combining these two variables. In this refined analysis, patients whose primary tumors have lower levels of both antigens evidently have a very low risk of relapse (93% disease-free survival at three years) in contrast to patients with high uPA and high PAI-1 (55% disease-free survival at three years). The combination of uPA and PAI-1 in our group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse. Consequently, more than half of the patients had less than a 10% probability of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01833260
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  • 16
    Electronic Resource
    Electronic Resource
    Toward a molecular understanding of human breast cancer: A hypothesis (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 83-94 
    Details
    ISSN: 1573-7217
    Keywords: mammary epithelial cells ; aging ; immortalization ; breast cancer ; telomeres ; p53 ; M1/M2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A rate limiting step in most metastatic breast cancers is the development of unlimited proliferative potential by mammary epithelial cells. We describe mechanisms by which these cells can attain this state. The two independent mortality mechanisms controlling fibroblast senescence and immortalization (M1 and M2) are also found in human mammary epithelial cells. However, although both p53 and Rb are involved in the M1 mechanism of fibroblast cellular senescence, in human mammary epithelial cells only p53 is involved. The M1/M2 mechanisms may be induced by the gradual loss of telomere ends that occur as normal cells divide. Loss of telomere ends may result in genomic instability and in altered gene expression due to heterochromatin changes in subtelomeric regions. Events which can abrogate p53 function are described, as is the current state of knowledge about the function of p53. All these factors are included in a molecular model for the onset of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662404
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  • 17
    Electronic Resource
    Electronic Resource
    Characterization of binding sites for a GnRH-agonist (buserelin) in human breast cancer biopsies and their distribution in relation to tumor parameters (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 37-46 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; gonadotropin-releasing hormone-analog ; GnRH ; receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gonadotropin-releasing hormone analogs (GnRH-A) have been added to the armentarium in the therapy of hormone-dependent breast cancer in premenopausal women. The effect of chronic GnRH-A-treatment in premenopausal women is based on the suppression of the hypothalamus-pituitary-ovarian axis and the reduction of sex-steroid serum levels. In addition, a number of experimental and clinical data have been accumulated indicating a direct action of GnRH-A on breast cancer cells and tissue. In this study we analyzed 235 human breast cancer biopsies for specific GnRH-A-binding. We demonstrate high affinity GnRH-A binding sites in human breast cancer tissues. The evaluation of clinical data showed no correlation of the level of GnRH-A-binding with classical tumor parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662399
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  • 18
    Electronic Resource
    Electronic Resource
    Cost-effectiveness of breast cancer screening: Preliminary results of a systematic review of the literature (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 113-118 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cost-effectiveness ; mammography ; medical resource allocation ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is now considerable concern that universal access to health care within realistic resource constraints requires some sort of cost-effectiveness analysis of given medical procedures and interventions. One such intervention is routine mammographic screening for breast cancer. Here, we report preliminary results from an ongoing project to conduct a systematic and comprehensive review and comparison of the published cost-effectiveness analyses of screening for the early detection of breast cancer. We examine 16 such studies, and compare two studies in detail to explain how differences in assumptions and in consideration of down-stream effects have caused the published results for apparently comparable breast cancer screening programs to span a broad range.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662136
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  • 19
    Electronic Resource
    Electronic Resource
    Larger axillary metastases in obese women and smokers with breast cancer- an influence by host factors on early tumor behavior (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 193-201 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; smoking ; obesity ; primary tumor ; estrogen receptors ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node-positive breast cancer. Both M/P ratios and M were larger in the 72 obese women and in the 40 nonobese smokers than in the 64 nonobese nonsmokers after control for other factors. Step-wise regression analysis demonstrated independent associations between M/P ratios and obesity (p = 0.0002), larger primary tumors (p〈0.0001), more positive nodes (p〈 0.0001), and smoking (p = 0.0268), as well as between M and obesity (p = 0.0201), larger primary tumors (p = 0.0093), and more positive nodes (p = 0.0001). Among the 104 nonobese women, smoking was associated both with larger M (p = 0.0257) and larger M/P (p = 0.0055). Our observations suggest more rapid growth by metastases in obese women and smokers with breast cancer, as well as earlier metastasis from their primary tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689833
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  • 20
    Electronic Resource
    Electronic Resource
    The ER-positive / PgR-negative breast cancer phenotype is not associated with mutations within the DNA binding domain (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 191-202 
    Details
    ISSN: 1573-7217
    Keywords: estrogen receptor ; breast cancer ; DNA binding domain ; gel-retardation analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used in vitro DNA binding assays as a measure of estrogen receptor (ER) function in human breast tumors. We found that the majority of ER+ (25 ER+/progesterone receptor [PgR]+, and 25 ER+/PgR−) tumors we examined were capable of binding consensus estrogen response element (ERE) oligonucleotides in this assay system. We found significant proteolytic activity in many of the tumors such that protease inhibitors were found to be essential during the preparation of tumor extracts. We next applied direct sequence analysis of the ER DNA binding domain of several of these tumors, and determined that the ER+/PgR− breast tumors did not contain mutations within the DNA binding domain which might explain their apparent discordant receptor phenotype. We did identify an alternatively spliced ER variant missing exon 3 of the DNA binding domain. This variant was unable to function as a transcriptional inducer of an estrogen-responsive reporter in a yeast assay system. Furthermore, the exon 3 ER deletion variant was expressed at equivalent levels in all of the ER+ breast tumors, so that it does not appear to be involved in the evolution of the ER+/PgR− breast cancer phenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689692
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  • 21
    Electronic Resource
    Electronic Resource
    Prognostic significance of p53 gene alterations in node-negative breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 225-235 
    Details
    ISSN: 1573-7217
    Keywords: p53 gene ; p53 protein ; breast cancer ; prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations in the p53 gene can play a role in the transformation of normal to malignant cells. Because these mutations are more frequently reported later in the course of transformation, their presence could reflect a greater malignant potential of the tumor and, thus, an increased probability of metastasis and recurrence after local therapy. In a pilot study using single-stranded conformation polymorphism analysis (SSCP), 200 node-negative breast tumors were examined for mutations in the region encompassing exons 5 through 9 of the p53 gene. Exons 5 through 9 were tested because they contain 80–90% of known p53 gene mutations. The tumors ranged in size from 1 to 3 cm. 28 tumors were found to have an abnormal band pattern on both initial and repeat analysis. 4 of these tumors were sequenced; 3 contained a p53 mutation and the 4th had a rare neutral polymorphism. Disease-free survival (DFS) at 5 years for women with tumors having an abnormal SSCP analysis was 57% (± 10%), compared to a 79% (± 3%) DFS for the group with a normal pattern. By the log rank test, this difference was highly significant, p ≤ 0.01. The relative risk of recurrence for the group with an abnormal SSCP pattern was 2.2. In a multivariate analysis including ER, PgR, ploidy, S-phase, age, and tumor size, an abnormal p53 by SSCP analysis and patient age were the only factors that independently predicted DFS at 5 years. Conclusion: Women with node-negative breast cancer who have tumors with alterations in the p53 gene, as indicated by SSCP analysis, have a significantly poorer prognosis and a higher rate of relapse at 5 years. The prognostic significance is maintained in a multivariate analysis including many established prognostic factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665800
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  • 22
    Electronic Resource
    Electronic Resource
    Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the development of mammary tumors induced by dimethyl-benz(a) anthracene in the rat (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 253-265 
    Details
    ISSN: 1573-7217
    Keywords: androgens ; breast cancer ; Depo-Provera ; medroxyprogesterone acetate ; microspheres ; poly[DL-lactide-co-glycolide] ; prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects for the treatment of advanced breast cancer which are comparable to those achieved with other forms of endocrine therapy. Using mammary tumors induced in the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the possibility that low dose MPA could prevent the development of these tumors. Single subcutaneous injection of Depo-Provera (crystalline suspension of MPA) or MPA encapsulated in biodegradable microspheres of 50 : 50 poly[DL-lactide-co-glycolide] was given 7 days before oral DMBA. While 63% of intact animals developed palpable mammary tumors within 85 days after DMBA administration, tumor incidence decreased to 28% and 23% in animals who had received 30 mg and 100 mg of Depo-Provera, respectively. The same amounts of MPA delivered in microspheres caused a further decrease in tumor incidence to respective values of 7% and 6%. Average tumor area, on the other hand, decreased from 4.89 cm2 in intact rats to about 0.75 (0.57–0.88) cm2 and approximately 0.20 (0.14–0.22) cm2 in the Depo-Provera and microsphere-treated groups, respectively. Using the 50 : 50 formulation of poly[DL-lactide-co-glycolide] designed to release MPA at a constant rate for a 4-month period, the serum MPA concentration at 3 months was measured at 4.99 ± 0.43 ng/ml. Such data suggest that administration of a low dose controlled-release formulation of MPA in 50 : 50 poly[DL-lactide-co-glycolide] microspheres could well be an efficient and well tolerated approach for the prevention of breast cancer in women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665803
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  • 23
    Electronic Resource
    Electronic Resource
    Paracrine interaction in co-culture of hormone-dependent and independent breast cancer cells (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 275-281 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; hormone-dependence ; growth factors ; cell culture ; cell growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A permeable solid support (Transwell Coll.) was used to develop serum-free co-cultures allowing paracrine interactions between hormone-dependent (MCF-7, ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. Both hormone-independent cell lines were able to stimulate the growth of the hormone-dependent lines, whereas the opposite was observed only in the case of BT20 co-culture with ZR75.1 cells. The cell growth stimulation observed in co-cultures could be abolished by the addition to the culture medium of an excess of transforming growth factor alpha (TGFα) or insulin-like growth factor I (IGF-I). Similarly, treatment with a neutralizing anti TGFα antibody impaired the growth stimulation exerted by hormone-independent cells on hormone-dependent cells. These results confirm the important role of paracrine interactions in control of the growth of human heterogeneous breast tumors and suggest that the main growth factors involved in such interactions are TGFα and probably some growth factors from the insulin-like growth factor family rather than IGF-I itself.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665805
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  • 24
    Electronic Resource
    Electronic Resource
    Exon skipping gives rise to alternatively spliced forms of the estrogen receptor in breast tumor cells (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 163-174 
    Details
    ISSN: 1573-7217
    Keywords: alternative splicing ; breast cancer ; estrogen receptor ; exon skipping ; mRNA variants ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have previously described three messenger RNA variants coding for the human estrogen receptor (ER) [1]. These variants were identified using the polymerase chain reaction to perform directed cloning of ER cDNAs synthesized from polyadenylated RNA extracted from the human breast cancer cell line T47D. Each of the variants is characterized by the precise deletion of a single exon within the protein coding region of this message and was presumably derived by inaccurate or promiscuous splicing of primary estrogen receptor transcripts. We report here the results of RNAse protection experiments which independently confirm the existence of these splicing variants in T47D cells. Similar analysis of RNA from MCF-7 cells also revealed the presence of variant ER transcripts, suggesting that they may be a common finding in tumor cell lines which express the estrogen receptor. However, attempts to identify splicing variants in a number of nominally ER-negative cell lines using either RNAse protection or PCR amplification were without success.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689689
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  • 25
    Electronic Resource
    Electronic Resource
    Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 217-224 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using a synthetic peptide substrate, tyrosine protein kinase (TPK) activity was measured in 21 tumors from patients with histologically confirmed breast cancer and in five normal breast tissues from patients undergoing reduction mammoplasty. In 20 of 21 cancer specimens, tumor was available to assess phosphotyrosine (PT) immunohistochemically. Breast cancer specimens possessed significantly more TPK activity than normal breast tissues (Cancer = 43.9 ± 3.1 pm/mg protein/min, [Mean ± S.E.M.]; Normal = 3.4 ± 0.9, p 〈 0.001). TPK activity was higher in the clinically more aggressive infiltrating ductal cancers compared to the less aggressive intraductal cancers (Infiltrating = 55.9 ± 5.8; Intraductal = 17.2 ± 3.4, p 〈 0.01). TPK activity in tumors with both infiltrating and intraductal histology was intermediate (34.0 ± 7.2). Significant correlation existed between membrane TPK enzymatic activity and PT expression by immunohistochemistry. There was no relationship between estrogen or progesterone receptor status and TPK activity or PT; however, TPK activity from node negative breast cancer tissue was significantly less than from node positive specimens (p 〈 0.01). We conclude that breast cancer specimens possess elevated amounts of TPK which correlate with PT expression, and that increased tyrosine phosphorylation appears to correlate with the biologic aggressiveness of the malignant tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665799
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  • 26
    Electronic Resource
    Electronic Resource
    Drug resistance to tamoxifen during breast cancer therapy (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 27-40 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; tamoxifen ; drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Breast cancer is the most common malignancy occurring in Western women, and is one of the leading causes of cancer mortality. The nonsteroidal antiestrogen tamoxifen has been shown to be an effective treatment for pre and postmenopausal women with all stages of the disease. Tamoxifen provides effective palliation when used to treat patients with advanced disease, and adjuvant tamoxifen therapy produces significant increases in both disease-free and overall survival (Early Breast Cancer Trialists Collaborative Group. Lancet 339:1-15, 71-85, 1992). Data from the laboratory have shown that the primary action of tamoxifen is tumoristatic rather than tumoricidal, and long-term therapy is therefore recommended. Unfortunately, many patients experience disease progression while taking tamoxifen. Some tamoxifen resistant tumors may remain sensitive to alternative endocrine therapies, while others may become refractory to any hormonal manipulation. Many models have been developedin vitro andin vivo to study the progression of breast cancer growth from tamoxifen sensitive to tamoxifen resistant. We and others have used long-term estrogen deprivation and long-term tamoxifen exposure to develop cell lines and tumors capable of growth in the presence of clinically relevant tamoxifen concentrations. Recently our laboratory has also shown that mutations in the estrogen receptor can cause an antiestrogen-occupied receptor to behave as though it were occupied by an estrogen. Breast cancer is a highly heterogeneous disease and it is likely that the mechanisms which cause tamoxifen resistant growth are equally heterogeneous. Several of the models from our laboratory and others which may contribute to an understanding of this complex phenomenon are discussed here.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00683191
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  • 27
    Electronic Resource
    Electronic Resource
    Estrogen receptors: Ligand discrimination and antiestrogen action (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 17-26 
    Details
    ISSN: 1573-7217
    Keywords: estrogen receptors ; antiestrogens ; tamoxifen ; breast cancer ; estrogen binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used affinity labeling, site-directed mutagenesis and regional chemical mutagenesis in order to determine regions of the estrogen receptor (ER) important in hormone binding, ligand discrimination between estrogens and antiestrogens, and transcriptional activation. Affinity labelling studies with the antiestrogen, tamoxifen aziridine and the estrogen, ketononestrol aziridine have identified cysteine 530 in the ER hormone binding domain as the primary site of labeling. In the absence of a cysteine at 530 (i.e. Cys530A1a mutant), C381 becomes the site of estrogen-competible tamoxifen aziridine labeling. Hence these two residues, although far apart in the primary linear sequence of the ER protein, must be close in the three-dimensional structure of the protein, in the ER ligand binding pocket, so that the ligand can reach either site. Site-directed and region-specific chemical mutagenesis have identified a region around C530 important in discrimination between estrogens and antiestrogens, and other mutants have allowed identification of residues important in hormone-dependent transcriptional activation. Some transcriptionally inactive ER mutants also function as potent dominant negative ERs, suppressing the activity of wild-type ERs at low concentrations. These studies are beginning to provide a more detailed picture of the ER hormone binding domain and amino acids important in ligand binding and discrimination between different categories of agonist and antagonist ligands. Such information will be important in the design of maximally effective antiestrogens. In addition, since there is now substantial evidence for a mixture of wild-type and variant ERs in breast cancers, our studies should provide insight about the bioactivities of these variant receptors and their roles in modulating the activity of wild type ER, and should lead to a better understanding of the possible role of variant receptors in altered response or resistance to antiestrogen and endocrine therapy in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00683190
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  • 28
    Electronic Resource
    Electronic Resource
    Modulators of cellular protein phosphorylation alter thetrans-activation function of human progesterone receptor and the biological activity of progesterone antagonists (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 41-56 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; phosphorylation ; progesterone receptor ; signal transduction ; steroid antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Addition of progesterone to breast cancer cellsin vivo increases phosphorylation of human progesterone receptor (PR), suggesting that phosphorylation has a regulatory role in producing the activated form of receptor. Kinetic analysis indicates that hormone-dependent phosphorylation is sequential and that early stages of phosphorylation(s) are closely associated with enhancement of PR-DNA binding while later stages are associated with atrans-activation function. Various agents that stimulate cellular protein phosphorylation (8-Br cAMP, okadaic acid, TPA) functionally synergize with progesterone to enhance progesterone-dependent PRtrans-activation in intact cells. These results suggest that protein phosphorylation does have a role in modulating thetrans-activation function of PRin vivo. They also demonstrate cross-talk between second messenger signal transduction pathways and nuclear steroid receptors. Whether the phosphorylated target that provides the link between these two signal transduction pathways is PR itself or another protein involved in PR-mediated gene transcription is not known. Positive cooperative interactions were also observed between cAMP signaling pathways and the progesterone antagonist RU486, that resulted in RU486 exerting substantial agonist activities. This ability of cross-talk between second messenger and steroid receptor signal transduction pathways to override the antagonistic effects of RU486 suggests a novel mechanism to explain the problem of resistance to clinically important steroid antagonists.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00683192
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  • 29
    Electronic Resource
    Electronic Resource
    Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 277-281 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; depression ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Depression is not an uncommon complaint of women with breast cancer and is usually assumed to be related to the cancer diagnosis itself or its treatment. As part of a prospective clinical trial of adjuvant therapy of node negative breast cancer, 301 patients treated and assessed by one oncologist (SEJ) were serially questioned for symptoms of depression in the first 6–12 months after completing initial treatment (surgery, radiation therapy, and/or chemotherapy). Two hundred and fifty-seven patients were evaluable for assessment of depression; 155 were receiving tamoxifen and 102 were not. Twenty-six patients had symptoms of depression including 23 (15%) treated with tamoxifen compared to 3 (3%) in the group not placed on tamoxifen (p 〈 0.005). Of the 23 patients with depression in the tamoxifen group, symptoms were temporally related to the initiation of therapy and occurred generally in the first 2 months of treatment. Eight patients had mild symptoms not requiring a dose reduction, 8 had significant depression requiring a dose reduction to relieve symptoms, and 7 required discontinuation of tamoxifen. We conclude that clinical depression as a side effect of tamoxifen therapy may be more common than previously believed and should be further rigorously investigated to confirm or deny our clinical impressions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665698
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  • 30
    Electronic Resource
    Electronic Resource
    Genetic alterations on chromosome 17 in human breast cancer: relationships to clinical features and DNA ploidy (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 231-239 
    Details
    ISSN: 1573-7217
    Keywords: amplification of ERBB2 ; breast cancer ; DNA ploidy ; chromosome 17 ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We analyzed DNA from 105 primary breast cancers to assess amplification of the ERBB2 gene and loss of heterozygosity (LOH) on chromosome 17 using 4 polymorphic markers, and investigated the relationships of these genetic alterations to clinicopathological characteristics including DNA ploidy. Amplification of the ERBB2 gene was observed in 28% of the tumors. ERBB2 was amplified in tumors of all clinical stages and amplification was significantly linked to lymph node metastasis. LOH atD17S5 was observed in 28 of 57 informative tumors, while 17 of 62 informative tumors showed allelic loss atTP53. Among the 37 tumors informative for both loci, 32% showed LOH at these loci and 49% retained both alleles, indicating that there was a significant relationship between LOH atD17S5 and atTP53. We also examined LOH at theD17S74 andNME1 loci on chromosome 17q. LOH atD17S74 andNME1 was observed in 20% and 22% of the informative tumors, respectively, but there was no significant association between LOH at these loci. Of the 4 loci tested, LOH atTP53, D17S74, andNME1 was associated with clinical stage. Lymph node metastasis was correlated with LOH atNME1. Moreover, allelic loss was more frequent in aneuploid tumors than in diploid tumors. These results suggest that certain combinations of genetic alterations on chromosome 17 may cooperate in the development and/or progression of breast cancer. Furthermore, it seems likely that analysis of these alterations in breast cancer patients may provide useful prognostic information.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666584
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  • 31
    Electronic Resource
    Electronic Resource
    Sixteen week dose intense chemotherapy for inoperable, locally advanced breast cancer (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 277-284 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; dose-intensity ; inflammatory breast cancer ; locally advanced breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Up to 15% of women with breast cancer have locally advanced disease at diagnosis. The poor response of these patients to local therapy alone and the frequent development of disseminated disease suggest that early intensive systemic therapy may benefit these women. Twenty-four patients with non-metastatic, locally advanced, primarily inflammatory, inoperable breast cancer were treated with a 16-week dose-intense chemotherapy regimen as induction therapy. Treatment consisted of 8 repetitive 2-week cycles consisting of 100 mg/m2 cyclophosphamide orally D1-7, 40 mg/m2 doxorubicin intravenously (IV) D1, 1 mg vincristine IV D1, 100 mg/m2 methotrexate IV D1, 10 mg/m2 leucovorin every 6 hours for six oral doses D2-3, and 600 mg/m2 5-FU IV over 2 hours D2. A continuous infusion of 300 mg/m2 5-FU per day was given IV D8-9 of each 2-week cycle. After induction all patients had at least a partial clinical response and were operable; 9/24 (37%) achieved a clinical complete response. All patients underwent at least a simple mastectomy. Pathologic examination revealed no evidence of gross macroscopic tumor in 11/24 patients (46%) and no evidence of microscopic disease in 4/24 patients (17%). Seven of 24 patients (29%) had no microscopic disease in the breast. At a median follow-up of 45 months, there have been 10 relapses in the 24 patients treated with this induction regimen. The actuarial relapse-free survival at 5 years is 58%. Actuarial overall survival at 5 years is 75%. We conclude that this regimen is safe and well-tolerated and that the results of this therapy are sufficiently promising to warrant further study of this regimen in patients with locally advanced breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666589
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  • 32
    Electronic Resource
    Electronic Resource
    Tumour cyclic AMP binding proteins: an independent prognostic factor for disease recurrence and survival in breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 89-94 
    Details
    ISSN: 1573-7217
    Keywords: prognosis ; breast cancer ; second messenger systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In two separate cohorts of breast cancer patients presenting without evidence of distant metastatic disease, high levels of tumour cyclic AMP binding proteins (〉 8 pmol/mg cytosol protein) have been shown to be associated with poor prognosis in terms of both disease recurrence and overall survival. This association is independent of known established prognostic factors and allows the identification of a small subgroup of patients whose outlook warrants the implementation of aggressive systemic therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682703
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  • 33
    Electronic Resource
    Electronic Resource
    The effect of tamoxifen on the endometrium (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 101-105 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endometrium ; tamoxifen ; ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tamoxifen is one of the most important treatments for breast cancer, especially in postmenopausal patients. It acts primarily as an anti-estrogenic agent, due to its cytoplasmic estrogen receptor binding capacity. However, it also exerts a mild estrogenic effect. Since the prolonged use of estrogen has been reported to increase the rate of benign and malignant changes in the endometrium, we evaluated whether there is a correlation between tamoxifen therapy and endometrial benign and malignant conditions. The study group comprised 95 patients with breast cancer who were treated with tamoxifen. No control group was examined. Patients underwent vaginal ultrasonography and endometrial biopsy in order to evaluate any changes in the endometrium occurring during tamoxifen therapy. Pathological changes were observed in 14 patients, 13 of whom were treated with tamoxifen for more than 12 months. Of these women, 3 were diagnosed with endometrial cancer, 3 had mild dysplasia, 3 had endometrial hyperplasia, and 4 had a benign endometrial polyp. Our findings indicate a significant correlation between long-term tamoxifen administration and endometrial proliferation. We therefore recommend that women treated with tamoxifen for more than 12 months have an annual vaginal ultrasonography and endometrial biopsy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682705
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  • 34
    Electronic Resource
    Electronic Resource
    An estrogen receptor genetic polymorphism and a history of spontaneous abortion — Correlation in women with estrogen receptor positive breast cancer but not in women with estrogen receptor negative breast cancer or in women without cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 175-180 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; genetics ; spontaneous abortion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We previously identified a polymorphism in the human estrogen receptor gene. In a preliminary study on women with estrogen receptor positive (ER+) breast tumors, we found that the presence of the rarer of the two alleles, the B' allele, is correlated with a history of spontaneous abortion. Because that study evaluated only women with estrogen receptor positive (ER+) breast cancer, it was unknown whether the observed correlation was restricted to the cancer group or was independent of breast cancer. We have now extended our analysis to include not only additional women with ER+ breast cancer, but also those with estrogen receptor negative (ER−) breast cancer and women without cancer. Results of the current study continue to show an association between the B' allele and a history of spontaneous abortion in the ER+ breast cancer group. There was no such correlation either in the ER− breast cancer group or in the group without cancer. Also, we continue to observe, in the ER+ breast cancer group, a significantly higher concentration of ER protein in tumors from homozygous wild type women (genotype BB), than in the tumors from women who are heterozygous for the rarer allele (genotype BB'). We conclude that the combination of spontaneous abortion and the BB' ER genotype may be a marker for breast cancer susceptibility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689690
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  • 35
    Electronic Resource
    Electronic Resource
    Dietary habits and mammographic patterns in patients with breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 207-215 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; dietary habits ; fat intake ; mammographic patterns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Between 1983 and 1986, dietary history interviews were conducted with 238 women aged 50–65 years who had surgery for stage I–II breast cancer. Diagnostic mammograms were coded in line with Wolfe's criteria in N1, P1, P2, and Dy patterns. Women with Dy pattern reported significantly higher intake of total fat, monounsaturated fatty acids (FA), polyunsaturated FA, n-3 FA, n-6 FA in per cent of energy (E%), and α-tocopherol in mg/10 MJ. Fat intake was lowest in women with N1 pattern and highest in those having Dy pattern. Patients having ER-rich cancers and Dy pattern reported significantly higher intake of total fat, monounsaturated FA, polyunsaturated FA, n-6 FA (E%), and α-tocopherol (mg/10 MJ), as well as significantly lower intake of carbohydrate (E%) and calcium (g/10 MJ). In the stepwise multivariate analysis, the multivariate-odds ratio (OR) for having P2 + Dy patterns was 1.06 (95% confidence interval (CI), 1.02–1.12) for each increment in E% of total fat. In women with ER-rich tumors this OR was 1.09 (95% CI, 1.02–1.16). The highest self-reported body mass index (BMI) was observed in women with N1 + P1 patterns. OR for having P2 + Dy patterns was 0.91 (95% CI, 0.83–0.98) for each increment in 1 kg/m2 of BMI. The results suggest that dietary habits affect the mammographic parenchymal pattern in women with breast cancer and that a high fat intake is associated with a higher proportion of mammograms with Dy pattern in such patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665798
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  • 36
    Electronic Resource
    Electronic Resource
    Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 247-252 
    Details
    ISSN: 1573-7217
    Keywords: platelet derived growth factor ; breast cancer ; immunohistochemistry ; prognosis ; tumor progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a study of plasma and tissue platelet derived growth factor (PDGF) concentration in patients with breast cancer, elevated levels of plasma PDGF were found in a significant proportion, 11/37 (30%), of patients. Sixteen patients (43%) had tumors which expressed PDGF-AA and 6 patients had tumors which in addition expressed the BB isoform of PDGF. All patients with elevated plasma levels of platelet derived growth factor had tumors which expressed the growth factor on immunohistochemical staining of tumor cells. Furthermore there was a significant correlation between plasma levels of platelet derived growth factor and the intensity of tissue staining. Patients with stage four breast cancer with tumors which were positive for platelet derived growth factor had a significantly lower response rate to chemotherapy as well as significantly shorter duration of survival. In addition, patients with stage four breast cancer who had elevated plasma PDGF levels had a significantly shorter survival. These results indicate that elevated plasma levels of platelet derived growth factor in patients with breast cancer are derived from the tumor cells and suggest that platelet derived growth factor may play a significant role in control tumor cell growth.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665802
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  • 37
    Electronic Resource
    Electronic Resource
    Expression of mdr1 gene in human breast primary tumors and metastases (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 267-274 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; metastasis ; multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Expression of mdr1 gene has been evaluated in 34 tumor samples obtained from breast cancer patients who were classified according to their treatment, and clinical follow-up. No gene amplification was found. mdr1-RNA was never detected in 29 primary breast tumors including 5 samples from patients previously treated by 6 courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC). On the other hand, mdr1-RNA expression was detected in 1 local recurrence and 2 out of 3 metastases, all of them being treated and exhibiting a poor evolution. A second, untreated local recurrence remained negative. Clinical follow-up for 7 to 48 months in patients receiving chemotherapy showed that absence of mdr1-RNA could not be an accurate factor of satisfactory response to chemotherapy. But, all the patients with detectable mdr1-RNA exhibited a poor evolution and response to treatment. In conclusion, evaluation of mdr1-RNA seemed to be of little interest in primary breast tumors. However, the concomitant presence of an mdr1-RNA and a metastatic phenotype could give a new insight into the relationship between invasive and resistance properties of cancer cells. Such situations would need to be analyzed very carefully for a better utilization of chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665804
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  • 38
    Electronic Resource
    Electronic Resource
    Protein tyrosine kinase activity as a prognostic parameter in breast cancer, a pilot study (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 283-287 
    Details
    ISSN: 1573-7217
    Keywords: protein tyrosine kinase ; breast cancer ; prognostic parameters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Protein tyrosine kinase (PTK) activity was assayed in cytosolic extracts from normal breast tissue, benign tumors, and 84 T1-T2, N0-N1 M0, breast carcinomas. Normal breast tissue extracts yielded an average value of 1.9 ± 1.1 pmol32P incorporated/min/mg protein, whereas a mean of 12.5 ± 6.1 was obtained for cancer samples. With a median follow-up of 34 months, in the series of 40 patients classified N-, PTK positive patients presented a significantly smaller 3-year disease free survival than the PTK negative ones. Multivariate analysis shows that PTK activity emerges as a potential prognostic factor in breast cancer (p = 0.02). These preliminary results will be updated on a bigger cohort of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665806
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  • 39
    Electronic Resource
    Electronic Resource
    Control of breast cancer cell growth by steroids and growth factors: Interactions and mechanisms (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 57-68 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; steroids ; growth factors ; interacting pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Over the past two decades, the simple model for control of breast cancer growth involving one or two factors acting directly or indirectly via endocrine pathways has turned into a complex model implicating numerous interacting factors and the diverse cell populations constituting breast tumors. Current approaches to breast cancer therapy now require integration of these multiple parameters and enhanced understanding of the different levels of their intricate interactions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00683193
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  • 40
    Electronic Resource
    Electronic Resource
    Frequency of spontaneous p53 mutations (CpG site) in breast cancer in Japan (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 247-252 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; Japan ; p53 mutation ; RT-PCR-SSCP ; sequencing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sxity-five tumors of invasive ductal carcinoma of the breast were examined for p53 alteration by the reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method and sequencing analysis. In total, 16 samples (24.6%) showed p53 gene alteration. Sixteen of these alterations were evaluated by sequencing analysis, and 15 showed missense point mutations while one showed a 9-base pair deletion. In the 15 point mutations, G:C to A:T transitions constituted the majority (53%), and five tumors (33%) had a transition at the CpG site, which are mutational patterns not commonly found in breast tumors from Europe and America. On the other hand, there were no G:C to T:A transversions in our cases, which were frequently observed transversions in Europe and America. These p53 mutation patterns in breast cancer in Japan are not similar to those in Europe and America reported by Hollsteinet al. and Coleset al.. These findings suggest that there are some differences between mechanisms of breast cancer in Japan and in Europe and America.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665694
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  • 41
    Electronic Resource
    Electronic Resource
    Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review (1993)
    Springer
    Breast cancer research and treatment 24 (1993), S. 185-193 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cancer progression ; extracellular matrix ; human carcinomas ; matrix metalloproteinases ; stroma ; urokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Stromelysin-3 (ST3) is a putative new matrix metalloproteinase (MMP) which may play a role in the progression of human carcinomas, and exhibits unique structural and functional characteristics among the MMP family. The ST3 gene, which is generally not expressed at significant levels in benign breast tumors, has been found to be expressed in all invasive breast carcinomas tested so far. The gene is also expressed in somein situ breast carcinomas, which have a higher probability to become invasive. ST3 RNA and protein are specifically found in fibroblastic cells immediately surrounding the neoplastic cells, both in invasive andin situ breast carcinomas. The same expression pattern is observed in other types of human carcinomas, and the highest ST3 RNA levels are observed in tumors that exhibit high local invasiveness. The ST3 gene is also expressed in fibroblastic cells during the inflammatory phase of wound healing, which suggests that ST3 gene expression in stromal fibroblasts may be under the control of factors produced by inflammatory cells during wound healing, and by cancer cells during carcinoma progression. ST3 may thus represent a stroma-derived factor necessary for the progression of epithelial malignancies, and its manipulation may possibly be used to develop new anti-cancer agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01833259
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  • 42
    Electronic Resource
    Electronic Resource
    The future of new pure antiestrogens in clinical breast cancer (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 1-9 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; antiestrogens ; tamoxifen ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The rationale for seeking to identify new pure antiestrogens was based on the recognition that existing antiestrogens, exemplified by tamoxifen, all possess partial agonist (estrogenic) activity. Conceptually, pure antiestrogens should be more effective than tamoxifen in ablating the mitogenic action of estrogens on breast tumor growth. The discovery and properties of the pure antiestrogens ICI 164,384 and ICI 182,780 are described and contrasted with those of tamoxifen. Key characteristics of these compounds which may be of particular relevance to their therapeutic application in the treatment of breast cancer are described. These include experimental data which predict efficacy in patients whose disease recurs during tamoxifen treatment, and the potential for pure antiestrogens to demonstrate greater efficacy than tamoxifen in first-line treatment of advanced breast cancer. The data imply that gains in efficacy could emerge as more rapid, more complete, or longer-lasting tumor remissions. Clinical trials with ICI 182,780 will reveal whether one or more of these predictions is correct.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662395
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  • 43
    Electronic Resource
    Electronic Resource
    Progesterone receptors in routinely paraffin-embedded primary breast carcinomas and lymph node metastases (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 47-55 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; progesterone receptor ; fixed tissue ; immunohistochemistry ; metastases ; lymph nodes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Described here is an immunohistochemical technique using the commercially available monoclonal progesterone receptor (PR) antibody KD 68 in routinely fixed and paraffin-embedded breast carcinomas and lymph node metastases. The authors' technique is compared with several incubation variations. The method applying the primary antibody in a dilution of 1:10 overnight followed by a biotinylated second antibody showed the best results when Triton X-100 was added to the buffer. Using this method, comparison with the results on frozen sections of 34 breast carcinoms yielded a significant concordance of 94%. Correlation between the results on paraffin sections and those obtained by the standard dextran-coated charcoal cytosol assay was 80%. The value of the method for predicting endocrine therapy response was shown in 20 patients. Thus the reliability of the method has been demonstrated and was applied on 151 lymph node metastases and the corresponding primary breast carcinomas from 50 patients. Generally PR content in the metastases was lower than in the primary tumors (p〈0.001). This finding indicates that evaluation of PR in lymph node metastases should be included in the decision for endocrine therapy of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662400
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  • 44
    Electronic Resource
    Electronic Resource
    Human recombinant interferon-βSER and tamoxifen: growth suppressive effects for the human breast carcinoma MCF-7 grown in the athymic mouse (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 141-150 
    Details
    ISSN: 1573-7217
    Keywords: interferon-beta ; tamoxifen ; breast cancer ; athymic mice ; estrogen receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tamoxifen is the endocrine treatment of choice for breast cancer. However, resistance to therapy and patient relapse inevitably occurs. In future treatment schedules, interferons could be administered with tamoxifen, in an attempt to prevent disease recurrence. Human recombinant interferon-βSER (rIFN-βSER) inhibited the growthin vitro of the estrogen receptor (ER) positive breast cancer cell line MCF-7 and the ER negative breast cancer cell line MDA-MB-231. This inhibitory effect was achieved at doses of 50U/ml and above. The growth of MCF-7 tumors in estradiol-stimulated athymic mice was greatly inhibited by high dose rIFN-βSER treatment (106U/day). In spite of the impressive antitumor effects upon MCF-7 tumors, rIFN-βSER had no effect upon ER levels within the tumors at either the RNA or protein level, as measured by Northern blotting and ER-EIA respectively. High dose rIFN-βSER (106U/day) did result in some inhibition in the growthin vivo of the tamoxifen-stimulated MCF-7 variant MCF-7 TAM, although not to the same extent as was observed with the estradiol-stimulated MCF-7 tumors. rIFN-βSER was also administered to animals bearing MCF-7 tumors and treated with estradiol and tamoxifen. In the animals undergoing high dose therapy (106U/day), tumor growth was completely suppressed. Furthermore, tumor growth continued to be suppressed in those animals in which the rIFN-βSER therapy was halted and the tamoxifen capsule removed. No tumors were observed in spite of the environment of estradiol stimulation. Thus, the combination of interferon and tamoxifen was totally growth suppressive for MCF-7 xenografts in nude mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00662139
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  • 45
    Electronic Resource
    Electronic Resource
    Medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone-receptor negative MFM-223 human mammary cancer cells via the androgen receptor (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 217-224 
    Details
    ISSN: 1573-7217
    Keywords: androgen ; breast cancer ; in vitro ; mammary cancer cells ; medroxyprogesterone acetate ; progesterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study demonstrates for the first time, that medroxyprogesterone acetate (MPA) inhibits the proliferation of the estrogen and progesterone receptor negative mammary cancer cell line MFM-223 via the androgen receptor. MPA is a progestin, which is used in the hormonal treatment of disseminated breast cancer. It binds to the progesterone, androgen, and glucocorticoid receptor and may exert its antiproliferative effects via different receptors. MFM-223 human mammary cancer cells contain a very high level of androgen receptors (160 fmol/mg protein) and low levels of estrogen, progesterone, and glucocorticoid receptors (〈20 fmol/mg protein). This cell line provides therefore a good model system to analyze the possible role of the androgen receptor in the action of MPA avoiding interference with other steroid hormone receptors. Effective inhibition of proliferation is achieved by 10 nM MPA or 1 nM of the androgen dihydrotestosterone, corresponding well to the binding affinities of both compounds (3.6 and 0.18 nM, respectively). The involvement of the androgen receptor was confirmed by competition experiments with antiandrogens. Furthermore, MFMDHT cells, which are an androgen resistant subline of MFM-223 cells, are also resistant to MPA. This data supports the involvement of the androgen receptor in the action of MPA and additionally rules out direct hormone-independent cytotoxic effects of MPA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689836
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  • 46
    Electronic Resource
    Electronic Resource
    Markers of prognosis in breast cancer - the relationship between binding of the lectin HPA and histological grade, SPF, and ploidy (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 247-256 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; glycosylation ; HPA ; Helix pomatia lectin ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Abnormal cellular glycosylation as demonstrated by the binding of a lectin fromHelix pomatia (HPA) to paraffin-embedded sections has been shown in several studies to be associated with aggressive biological behaviour and poor long-term patient prognosis in breast cancer. This study aims to address the possibility that expression of the HPA binding ligand may be of prognostic significance through an association with increased cellular proliferation (as measured by S-phase fraction and histological grade), anaplasia (reflected in histological grade), or ploidy (DNA index). In a 24 year retrospective study, paraffin-embedded sections of 366 primary breast cancers were stained for binding of HPA. All tumours were assessed for histological grade. Flow cytometry was performed on all cases for which sufficient tumour tissue was available (358/366 cases) and S-phase fraction (SPF) and ploidy calculated. Data regarding patient age at diagnosis, nodal status, and tumour size were also recorded. Life table analyses revealed survival advantage for HPA ‘non stainers’ in comparison to ‘stainers’ (p〈 0.001); for patients with tumours of low grade vs. high grade (p〈0.001); and for those with tumours of low SPF vs. high SPF (p〈0.001). No survival advantage was shown for those with diploid vs. aneuploid tumours (p= 0.17). No association was apparent between HPA binding and grade, SPF, or ploidy (Chi squared values not significant). This was confirmed by multivariate analysis in which nodal status, tumour size, and SPF were independently predictive of survival. There was no confounding effect of grade, SPF, or ploidy upon the correlation between survival and HPA binding. HPA was, however, not independently predictive owing to its strong association with nodal status. The results of this study suggest that the prognostic significance of altered glycosylation, as detected by HPA binding, is unlikely to be through an association with proliferative rate, degree of anaplasia, or cellular ploidy, but may rather be through a direct association with the presence of nodal metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689839
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  • 47
    Electronic Resource
    Electronic Resource
    Design of preparative regimens for stem cell transplantation in breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. S3 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cisplatin ; cyclophosphamide ; etoposide ; mitoxantrone ; stem cell transplantation ; thiotepa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have evaluated tandem cycles of a tri-drug combination, termed CVP (cyclophosphamide, etoposide [VP-16], and cisplatin [Platinol]), at four levels in more than 300 patients with various types of tumors. Tandem CVP appears to be at least therapeutically equivalent to alternatives. A second potentially noncross-resistant combination of mitoxantrone and thiotepa (MT), with or without etoposide, has been used in sequence following CVP to improve long-term, disease-free survival in patients who have multiple metastatic sites, who relapse shortly after adjuvant therapy, or who show other unfavorable clinical features. A combination of MT and etoposide (MVT) achieved an overall response rate of 61% in 32 patients with metastatic or refractory breast cancer. The etoposide was then eliminated to decrease the major toxicities of this regimen. MT was subsequently given to 37 evaluable patients prior to bone marrow infusion. The overall response rate was 48.5%. Thirty patients with metastatic breast cancer were then treated with induction therapy, a cycle of CVP, and then a cycle of MT. Given the low complete remission (CR) rate to induction therapy in these patients, the CR rate achieved with CVP-MT was encouraging. Further studies are ongoing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668354
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  • 48
    Electronic Resource
    Electronic Resource
    Inhibition of growth and appearance of estrogen-dependent rat mammary tumors by 10-propargylestr-4-ene-3,17-dione, an aromatase inhibitor (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 15-21 
    Details
    ISSN: 1573-7217
    Keywords: aromatase ; aromatase inhibitors ; breast cancer ; estrogen ; estrous cycle ; tumor regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aromatase inhibitor 10-propargylestr-4-ene-3,17-dione (PED) has been evaluatedin vivo as an anticancer agent. Prolonged administration of PED to rats bearing dimethylbenzanthracene-induced mammary tumors resulted in significant regression of hormone-responsive tumors within several days. Greater than 50% regression was generally observed after 14 days of treatment, irrespective of dose (1, 5, or 50mg/kg body weight/day). In addition to tumor regression, a significantly increased incidence in tumor stasis was observed over the course of PED treatment. While all doses of PED examined were equipotent for both tumor regression and stasis, a dose-dependent inhibition of new tumor formation was observed in PED-treated rats. In control animals an average of 1.2 new tumors was observed during the experimental period; in contrast, averages of 0.5 tumors appeared in animals receiving 1mg PED/kg body weight/day, 0.1 tumors at 5 mg/kg, and at 50mg of PED/kg body weight/day, no new tumors occurred during the time PED was administered. The effects of PED on both regression of existing tumors and appearance of new tumors were reversed by co-administration of estradiol. Thus, PED impairs estrogen-dependent mammary tumor growth, resulting in cessation of new growth and regression of responsive tumors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682696
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  • 49
    Electronic Resource
    Electronic Resource
    Relationship between immunological parameters and survival of patients with liver metastases from breast cancer given immuno-chemotherapy (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 55-65 
    Details
    ISSN: 1573-7217
    Keywords: autologous tumor killing activity ; breast cancer ; immuno-chemotherapy ; interleukin-2 ; mixed lymphocyte tumor reaction ; natural killer cell activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We treated 33 patients with liver metastases from breast cancer by immuno-chemotherapy including adoptive cell transfer between 1987 and 1992. In this study, we examined the change of immunological parameters in the peripheral blood lymphocytes and interleukin-2 (IL-2)-cultured lymphocytes, in primary vs. metastatic breast cancer patients and before vs. after treatment. Moreover, we examined their correlation with therapeutic response and survival after treatment. The immunological parameters used werein vitro natural killer cell activity (% lysis of K562),in vitro autologous tumor-killing activity (% lysis against autologous freshly isolated tumor cells), and proliferation of lymphocytes stimulated with IL-2 and autologous sonicated tumor extract antigen in mixed culture (IL-2-enhanced MLTR). When compared with primary breast cancer patients, patients with liver metastases showed a significant decrease in % lysis of K562 and autologous tumor cells. After treatment, the stimulation index in IL-2-enhanced MLTR increased significantly from the pretreatment level and correlated with survival after treatment. Moreover, non-specific immunological parameters (performance status, lymphocyte count, and transferred cell count and proliferation rate of cultured lymphocytes) were significantly associated with response and prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682700
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  • 50
    Electronic Resource
    Electronic Resource
    The role and prognostic significance of p53 gene alterations in breast cancer (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 95-102 
    Details
    ISSN: 1573-7217
    Keywords: p53 ; tumor suppressor genes ; breast cancer ; prognosis ; progression ; gene alterations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alterations in the p53 tumor suppressor gene are the most frequent genetic changes found in breast cancer, with an incidence reported in a range of 15 to 50%. The incidence of p53 alterations is approximately 15% for in situ carcinoma, while for invasive node-positive disease it is 2 to 3 times higher. This high rate of alteration suggests that the gene plays a central role in the development of breast cancer. The p53 gene functions as a negative regulator of cell growth. Alterations in the gene lead to loss of its usual negative growth regulation and more rapid cell proliferation. Since p53 alteration can reflect a more advanced state of progression and a higher rate of proliferation, breast tumors that have a p53 alteration could have a greater probability of having micrometastasis. p53 alterations could therefore be a prognostic factor for recurrence after primary local therapy. Consistent with this hypothesis, several independent studies using different methodologies have found that breast tumors with altered p53 have a worse prognosis and are also more likely to have other poor prognostic factors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00683196
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  • 51
    Electronic Resource
    Electronic Resource
    Intrapleural adaptive immunotherapy for breast cancer patients with cytologically-confirmed malignant pleural effusions: an analysis of 67 patients in Kyoto and Shiga Prefecture, Japan (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 203-210 
    Details
    ISSN: 1573-7217
    Keywords: adoptive immunotherapy ; breast cancer ; chemotherapy ; interleukin-2 ; OK-432 ; pleural effusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively. The patients received their first thoracentesis between 1980 and 1990. Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2. Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1). Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p 〈 0.01). Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p〈 0.001) difference in survival. Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p 〈 0.005) factor to prolong the survival of the patients among several prognostic factors. Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665690
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  • 52
    Electronic Resource
    Electronic Resource
    An evaluation of clinical follow-up in women with early stage breast cancer among physician members of the American Society of Clinical Oncology (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 211-219 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; follow-up ; physician practice patterns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Routine clinical follow-up for distant metastatic disease among women with early stage breast cancer is of uncertain clinical benefit. In order to evaluate current practice patterns, we administered a mailed survey to a stratified random sample of physician members of the American Society of Clinical Oncology (ASCO) (N = 435). The survey assessed the frequency and motivation for ordering follow-up medical tests in asymptomatic postmenopausal women with stage I or II breast cancer. The response rate was 55%, distributed as 39% radiation oncologists, 32% medical oncologists, and 29% surgeons. In the first year after treatment, physicians performed, on average, one physical examination every 3 months, one blood panel (CBC, alkaline phosphatase and liver function tests) every 4 months, and one chest radiograph every 9 months. In addition, 38% of the respondents ordered CEA and 21% ordered CA 15-3 levels, 28% ordered bone scans, and less than 4% ordered CT scans, bone surveys, or bone marrow biopsies in the first year after treatment. A logistic regression analysis controlling for physician age, gender, sub-specialty, practice type, years of experience, number of breast cancer patients treated annually, geographic region, and community size, showed that surgeons were less likely to order blood tests (p 〈 0.001) and tumor markers (p 〈 0.0029) than medical oncologists in years 3 and 5 of follow-up. Compared to physicians practicing in the northeast, those from the midwest were less likely to order chest radiographs in year 3 of follow-up (p = 0.0028). Other provider characteristics had no significant effect on test ordering behavior. The results of this survey suggest that relatively uniform practice patterns in regard to the follow-up of postmenopausal women with early stage breast cancer exist among ASCO physicians.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665691
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  • 53
    Electronic Resource
    Electronic Resource
    The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients (1993)
    Springer
    Breast cancer research and treatment 27 (1993), S. 253-262 
    Details
    ISSN: 1573-7217
    Keywords: dietary fat ; breast cancer ; estrogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15–20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (≥ 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p 〈 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665695
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  • 54
    Electronic Resource
    Electronic Resource
    Characteristics of the combination paclitaxel plus doxorubicin in breast cancer cell lines analyzed with the ATP-Cell Viability Assay (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 21-27 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; paclitaxel ; doxorubicin ; MCF-7 ; T47D ; BT-20 ; chemosensitivity testing ; ATP-Cell-Viability Assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Preliminary clinical data show promising activity regarding the combination of paclitaxel (TaxolTM) (TAX) and doxorubicin (AdriamycinTM) (ADR) in the treatment of breast cancer. This combination needs both further preclinical and clinical investigations to better understand the drug interaction, and to optimize the dose and schedule of these drugs. This study was done to evaluate the combination effect of TAX and ADR in three human breast cancer cell lines. The ATP-Cell-Viability Assay was used to evaluate the chemosensitivity profiles and to obtain dose response curves. For quantitation of synergism and antagonism the median-effect principle was applied and the corresponding combination index values were calculated. Drug synergism/antagonism was shown to be dose-related; synergism was enhanced at higher fractions affected. From this preclinical data, we have concluded that TAX-ADR is highly effective and partly synergisticin vitro. In spite of severe initial toxicities in early clinical trials in metastatic breast cancer patients, further clinical studies appear to be justified in order to define a tolerable dosage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666352
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  • 55
    Electronic Resource
    Electronic Resource
    Familial effects of prostate and other cancers on lifetime breast cancer risk (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 107-113 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endometrial cancer ; families ; lifetime risks ; ovarian cancer ; prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lifetime probabilities of developing breast cancer were calculated for first-degree female relatives of three groups of breast cancer patients: 114 with bilateral cancer, 186 unselected, and 88 males. The patients were classified according to whether they had a family history of prostate, endometrial, or ovarian cancer, or no family history of these cancers. In families of unselected female and male patients with no family history of prostate, endometrial, or ovarian cancer, the lifetime probability of developing breast cancer was 11.4%. The risk increased slightly to 13.5% when these other cancers may or may not have present (i.e., they were ignored, which is the usual method in computing risks) and increased further to 25.5% when prostate, endometrial, or ovarian cancer was present in the family. In families of patients with bilateral cancer the respective risks were 10.9%, 17.3%, and 34.4%. A family history of prostate cancer increased lifetime risk consistently in each of the groups, to 29.0% in the unselected and male groups and to 38.2% in the bilateral group. Endometrial cancer increased risk only in the bilateral group (to 41.8%) as did ovarian cancer (to 54.6%). Increased risk of breast cancer with a family history of endometrial or ovarian cancer appeared to be influenced by families with hereditary breast-ovarian cancer or the cancer family syndrome. The results indicate that prostate cancer, and endometrial and ovarian cancers in some families, can significantly increase breast cancer risk and should be taken into account when counseling women about their breast cancer risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666423
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    Electronic Resource
    Recent trends in breast cancer incidence, mortality, and mammography (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 97-106 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; early detection ; incidence ; mammography ; mortality ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The recent trends in mammography, and in breast cancer incidence and mortality, demonstrate the impact of an effective cancer control effort. The number of women over age 40 years who have ever had mammography has increased over 200% since 1980. Concomitantly, breast cancer incidence has increased about 32%, with nearly all of the increase in early stage disease. Analytic studies of these changes have demonstrated persuasively that the vast majority of this increase is temporary and is attributable to the lead-time afforded by mammography. As a result of this early detection and treatment of breast cancer, mortality has begun to decline in 1991–92. Although the search for practical preventive measures should continue, the benefits of early detection can be realized now. Further research is needed to define age groups most appropriately screened and the optimum intervals for screening.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666422
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  • 57
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    Electronic Resource
    Enzyme-linked immunosorbent assay of urokinase-type plasminogen activator (uPA) in cytosolic extracts of human breast cancer tissue (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 223-229 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cytosols ; ELISA ; urokinase-type plasminogen activator
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The enzyme urokinase-type plasminogen activator (uPA) plays a role in cancer invasion, and high levels of uPA in detergent extracts of mammary cancer tissue have been reported to be associated with a poor prognosis. We have explored the possibility of using mammary cancer cytosol extracts routinely prepared for steroid receptor analysis for retrospective prognostic studies of uPA. A sandwich enzyme-linked immunosorbent assay (ELISA) for uPA was developed, using polyclonal catching antibodies and a mixture of three biotinylated monoclonal detecting antibodies, that were selected to recognize free uPA, inhibitor-bound uPA, and uPA bound to its cell surface receptor. The assay detects active uPA and its inactive proenzyme form, pro-uPA, equally well. The limit of detection is approximately 1 pg of pro-uPA in a volume of 100 µl, and there is a linear dose-response up to 100 pg pro-uPA. The efficiency in extracting uPA of a neutral non-detergent buffer used to prepare cytosol extracts was compared with that of 4 other buffers. There was a pronounced difference in the efficiency, the most efficient being a pH 4.2 buffer containing the non-ionic detergent Triton X-100, while the least efficient was the buffer used to prepare cytosols. Nevertheless, uPA immunoreactivity was readily measurable in the cytosols, and there was a close correlation between the amounts of uPA extracted under optimal conditions and those routinely used for steroid hormone receptor analysis. While the amount of uPA extracted under the latter conditions constituted only about 12% of that optimally extractable, we conclude that the ELISA described herein can be used to retrospectively analyze the potential prognostic value of uPA-concentrations in cytosols prepared for analysis of steroid hormone receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666583
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  • 58
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    Electronic Resource
    Expression of the pS2 gene in normal breast tissue (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 295-297 
    Details
    ISSN: 1573-7217
    Keywords: pS2 ; normal breast ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary pS2 expression in normal breast tissue removed for cosmetic reasons was significantly lower than in uninvolved breast tissues from mastectomies for breast carcinomas. It is speculated that the presence of the carcinoma, or factors related to its development, could be the reason for this difference.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666592
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  • 59
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    Electronic Resource
    High DNA content and prognosis in lymph node positive breast cancer. A case control study by the university of Leiden and ECOG (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 1-8 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA aneuploidy ; LEYTAS ; image cytometry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate whether breast cancer cells with unusually high nuclear DNA content are associated with an adverse outcome, Eastern Cooperative Oncology Group investigators selected breast cancer trial patients who suffered an early death (ED) within two years after diagnosis to compare with other trial patients who had a survival of at least 7.5 years. Paraffin blocks of primary breast cancers were obtained from 93 evaluable patients who had been enrolled in two surgical adjuvant trials for lymph node positive (LN +) disease (T1-3N1M0). Single cell monolayer preparations from these blocks were stained with acriflavine-Feulgen and analyzed by image analysis for DNA content with the automated Leiden Television Analysis System (LEYTAS). Standard prognostic variables (estrogen receptor (ER) status, number of lymph nodes with metastases, and size of the cancer) were compared with three DNA content characteristics: DNA ploidy status, number of nuclei with 〉 5C DNA content, and percent of nuclei with 〉 5 C. Estimates of the odds ratio in multivariate comparisons showed that ER negativity was associated with ED (p = 0.0005) and an odds ratio estimate using negative/positive of 4.87. The number of positive lymph nodes associated with ED had a p-value of 0.0005 and an odds ratio estimate of 4.63 when comparing the 〉 3 nodes group to the 1–3 nodes group. In contrast, the strongest association for any of the DNA content characteristics with ED had a p-value of 0.017 and an odds ratio estimate of 2.76. This power of association disappeared when stratified on ER status. Therefore, the presence of breast cancer cells with highly aneuploid (i.e. 〉 5 C) DNA content does not possess independent prognostic information in LN + breast cancer. An association remains to be tested in lymph node negative breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666350
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  • 60
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    Electronic Resource
    DNA flow cytometry and breast cancer (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 51-53 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA flow cytometry ; ploidy ; prognostic factors ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Measurement of cellular DNA content by flow cytometry is capable of detecting aneuploid stemlines, and also of giving an indication of tumor proliferation kinetics by approximating the percentage of cells in S-phase of the replicative cycle. Because it can be applied both to fresh frozen material submitted for steroid hormone receptor analysis and to fixed paraffin-embedded blocks, it is particularly well suited to the study of breast cancer. Despite being a relatively straightforward test which is now widely used in the risk assessment of patients with early breast cancer, in common with many other prognostic markers its precise clinical role remains uncertain. An extensive body of published data has appeared in the last few years, but the results often appear to be inconclusive or contradictory. In order to define the prognostic significance of DNA cytometry in malignant diseases of the breast, large bowel, bladder, prostate, and hematopoietic system, and to clarify some of the technical issues related to clinical laboratory standards and quality controls, a DNA Cytometry Consensus Conference was held in Prout's Neck, Maine, on October 1–4, 1992. This meeting was sponsored by the NCI, the International Society for Analytical Cytology, and industry. The significance of the meeting's conclusions for clinical breast cancer are discussed here. The consensus statement regarding the clinical utility of DNA cytometry in breast cancer, and the Guidelines for the Implementation of Clinical DNA Cytometry which were generated at this meeting, also appear in this issue of Breast Cancer Research and Treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666356
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  • 61
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    Electronic Resource
    Clinical value of enzyme immunoassay of epidermal growth factor receptor in human breast cancer (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 215-221 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; prognostic factors ; enzyme immunosassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirtynine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%: cut-off level 10 fmol/mg protein) by BA, and 31 of 80 (38.9%: cut-off level 5 fmol/mg protein) by EIA. Agreement on EGFr status was 72.3% (68/94) between ICA and BA, 77.0% (57/74) between BA and EIA, and 73.8% (59/80) between EIA and ICA. These discrepancies are based on assay differences and the heterogeneous distribution of cancer cells within specimens. Regardless of the assay method used, EGFr status had a significantly negative correlation with estrogen receptor status. Although EGFr-ICA and BA status had no relationship with prognosis, patients with medium and high EGFr-EIA level tumors (over 5 fmol/mg protein) had shorter relapse-free periods than those with low level tumors. However, the prognostic value of positive EGFr-EIA status was weaker than that ofc-erbB-2 overexpression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666582
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  • 62
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    Electronic Resource
    Effect of oestrogen receptor status and time on the intra-tumoural accumulation of tamoxifen and N-desmethyltamoxifen following short-term therapy in human primary breast cancer (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 241-250 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; intra-tumoural tamoxifen ; oestrogen receptor status ; short-term therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary While the presence of oestrogen receptors (ERs) in human breast cancer may determine the biological response to tamoxifen, the extent to which ER status governs tumour tamoxifen accumulation is unclear. We investigated the intra-tumoural disposition of tamoxifen (TAM) and its major metabolite N-desmethyltamoxifen (DMT) in 36 human breast carcinomas following short-term therapy. Steady-state serum concentrations appeared to be reached following 2 weeks therapy, after which no significant difference in the intratumoural concentrations of TAM between ER − ve and ER + ve tumours was observed (717.9 ± 166.4 ng/gm, and 518.6 ± 109.4 ng/gm, respectively). In patients treated for less than 2 weeks, there was significantly less intra-tumoural TAM in ER − ve compared with ER + ve tumours (120.9 ± 49.9 ng/gm and 450.1 ± 75.3 ng/gm, respectively; p 〈 0.04). The rate of tumour TAM accumulation correlated with duration of therapy only for ER − ve tumours (r = 0.72, p 〈 0.02), whereas for ER + ve tumours the absolute ER value appeared to be weakly associated with TAM accumulation (r = 0.41; p 〈 0.05). The intra-tumoural ratio of TAM to DMT reflected the serum concentrations in ER − ve tumours, but in ER + ve tumours relatively more TAM to DMT was observed. A similar intracellular distribution of both TAM and DMT was observed, although following 2 weeks therapy relatively less of each compound was found in the cytosol of ER − ve compared with ER + ve tumours (18% vs 34%). These results demonstrate that ER status may influence the rate of accumulation and intra-cellular distribution of tamoxifen and its metabolites, but not the final concentrations which are achieved. Following steady-state, both ER + ve and ER − ve tumours, not all of which would be expected to respond to the drug, achieve intra-tumoural concentrations 5–7 fold greater than serum. Unlike recent reports on acquired resistance, therefore,de novo resistance to tamoxifen is unlikely to represent an inability of the tumour to achieve adequate intra-tumoural concentrations of the drug or its metabolites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666585
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  • 63
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    Electronic Resource
    Mitoxantrone, vincristine, and 5-fluorouracil with leucovorin modulation as induction chemotherapy prior to high-dose intensification in metastatic breast cancer (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 291-294 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; induction chemotherapy ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We treated 39 women with newly diagnosed stage IV breast cancer with a new regimen of mitoxantrone 18 mg/m2 on days 1, 29, 57, vincristine 1.4 mg/m2 (maximum 2.0 mg) on days 1, 8, 15, 22, 29, 36, 43, 50, and 5-fluorouracil 375 mg/m2 on days 15–20, 43–47, 71–75 with leucovorin modulation 500 mg/m2 before each 5FU infusion (MVF). This regimen was utilized as an initial cytoreductive or induction program for these patients prior to high-dose intensification with autologous stem cell rescue. Ten patients (25%) obtained a clinical complete response and six patients (15%) obtained a partial response for an overall response rate of 40%. In addition, 10 patients had evaluable disease that was improved or stable (primarily bone and/or bone marrow metastases) after MVF induction. Thus, 26 patients (65%) were eligible for high-dose intensification with autologous stem cell rescue after MVF induction. Toxicity was primarily a mild mucositis and more commonly peripheral neuropathy. MVF therapy is an active treatment program for metastatic breast cancer but the neurotoxicity makes it difficult to recommend for widespread use.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666591
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  • 64
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    Electronic Resource
    Advantages of magnetic resonance imaging in breast surgery treatment planning (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 257-264 
    Details
    ISSN: 1573-7217
    Keywords: MRI ; breast cancer ; imaging ; surgery ; staging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preoperative magnetic resonance imaging (MRI) was performed in 40 patients with malignant and benign breast tumors. Images were qualitatively evaluated to determine features of MRI that would benefit breast surgery treatment planning. MRI was found to be exceptional in demonstrating the relationship of tumors with respect to structures such as the chest wall, nipple, and skin. Tumor size was estimated by MRI, mammography, and gross pathological measurement in the 32 patients confirmed to have a malignant tumor of the breast. MRI estimated the tumor size to be larger than mammography in 71% of the cases and larger than pathological measurement in 84% of the cases. Compared with the standard method for determining tumor size (pathological measurement), MRI would have upstaged 22% of the evaluated cases from T1 to T2 and 10% of the cases from T2 to T3. MRI may prove useful in selecting patients for breast conserving therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689840
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  • 65
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    Pharmacokinetic/pharmacodynamic interactions of intensive cyclophosphamide, cisplatin, and BCNU in patients with breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. S11 
    Details
    ISSN: 1573-7217
    Keywords: autologous hematopoietic cell support ; BCNU ; breast cancer ; carboplatin ; cisplatin ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Combinations of alkylating agents in intensive doses with autologous hematopoietic cell support (AHCS) are commonly used to treat advanced, solid tumors. Relatively little is known about the pharmacokinetic or pharmacodynamic aspects of their use. The cyclophosphamide, cisplatin, and BCNU (CPA/cDDP/BCNU) regimen is often used in patients with breast cancer. In these individuals, the blood levels of BCNU vary by more than tenfold. In rats given BCNU, the blood level variability is associated with cisplatin pretreatment, and mean levels are much higher than those that occur when cisplatin pretreatment is omitted. These observations suggest that a major elimination pathway for BCNU is metabolic and is subject to cisplatin disruption. Between 30–50% of patients receiving the CPA/cDDP/BCNU regimen experience a steroid-responsive pulmonary injury that can be fatal if untreated. Blood levels of BCNU are positively correlated with the risk of pulmonary injury in these patients. Others have demonstrated that blood levels of CPA can be inversely correlated with the likelihood of cardiac toxicity and 2-year, relapse-free survival in patients with breast cancer. Emerging data suggest that circulating drug levels, rather than the calculated dose, best explain the variability of outcome in patients treated with combination alkylating agents and AHCS.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668355
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  • 66
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    DNA ploidy and helix pomatia lectin binding as predictors of regional lymph node metastases and prognostic factors in breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. 67-75 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA ploidy ; HPA staining ; lymph node metastasis ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was designed to evaluate whether DNA ploidy and/orHelix pomatia lectin (HPA) staining would be useful for predicting regional lymph node metastases and patients' prognosis in 106 patients with invasive breast cancer. The combination of DNA ploidy and HPA staining correlated better with regional lymph node metastases than DNA aneuploidy or HPA staining alone. DNA ploidy and HPA staining in combination correlated strongly with overall and disease-free survival by univariate analysis. However, the prognostic significance of DNA ploidy and HPA staining in combination was lost in multivariate analysis when regional lymph node metastases were introduced into the models. This emphasized the relationship in survival between regional lymph node metastases and the combination of DNA ploidy and HPA staining. We therefore concluded that the combination of DNA ploidy and HPA staining might provide prognostic information for breast cancer patients in whom regional lymph node dissection has not been performed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682701
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  • 67
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    Electronic Resource
    The prognostic effect of histological tumor grade in node-negative breast cancer patients (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 235-245 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; Cox regression ; histologic tumor grading ; node negative ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prognostic effect of histological tumor grade was evaluated in 1036 patients with early breast cancer (pT1 pN0 M0) entered into a trial comparing mastectomy and breast preserving treatment. All analyses were adjusted for the factors treatment, patients' age, and tumor size. Tumor grade was defined according to Bloom and Richardson based on the sum of scores assigned to each of three histological features: 1) degree of differentiation, 2) pleomorphism, and 3) mitotic index. The relative importance of these factors with regard to disease-free survival was evaluated. In univariate as well as in multivariate analyses the pleomorphism was the only factor showing a significant effect (univariate: p=0.0024, multivariate: p=0.015). It was investigated how the factors should be combined to define a histological grading score which yields the best possible classification of the patients with respect to prognosis. A new grading system was defined splitting the patients into three groups: 1) pleomorphism 1; 2) pleomorphism 2 or pleomorphism 3 and mitotic index 1; 3) pleomorphism 3 and mitotic index 2 or 3. This yields a good classification of the patients with respect to prognosis (p=0.0004). The prognostic effect of this score was compared with the effects of the grading systems proposed in the literature. According to Bloom and Richardson and in the modified version by Schauer and Weiss, grading is based on the sum of scores of the various histological factors. Therefore, the strong effect of the pleomorphism was diluted in these grading definitions (Bloom and Richardson: p=0.03, Schauer and Weiss: p=0.028). The grading system proposed by Le Doussalet al. consists only of the scores of pleomorphism and mitotic index (p=0.014). In summary, the factor pleomorphism showed a stronger effect on disease-free survival by itself than the grading systems proposed in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689838
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  • 68
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    Electronic Resource
    Autologous graft-versus-host disease: immunotherapy of breast cancer after bone marrow transplantation (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. S31 
    Details
    ISSN: 1573-7217
    Keywords: autologous graft-versus-host disease ; autologous bone marrow transplantation ; breast cancer ; cyclosporine A ; interferon gamma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and laboratory evidence of a dose-response relationship has prompted the investigation of highdose therapy with bone marrow transplantation in the treatment of women with metastatic breast cancer. Remission rates are high, but only a small proportion appear durable. An antitumor effect is associated with allogeneic graft-versus-host disease (GVHD) as well as with a similar syndrome that can be induced following autologous transplantation (autologous GVHD) by treatment with cyclosporine A following marrow infusion. The clinical manipulation of autologous GVHD may increase the potency of high-dose therapy. Clinical studies indicate that autologous GVHD can be induced in women with breast cancer and can be augmented by the administration of interferon gamma. Preliminary evidence indicates associated antitumor activityin vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668358
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  • 69
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    Electronic Resource
    Long-term follow up of breast cancer patients treated for hypercalcaemia with aminohydroxypropylidene bisphosphonate (APD) (1993)
    Springer
    Breast cancer research and treatment 25 (1993), S. 277-281 
    Details
    ISSN: 1573-7217
    Keywords: aminohydroxypropylidene bisphosphonate (APD) ; bisphosphonates ; breast cancer ; hypercalcaemia ; skeletal metastases ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary No systematic data are available about the long-term follow up of breast cancer patients treated with aminohydroxypropylidene bisphosphonate (APD) for hypercalcaemia and about the results of APD treatment of recurrent hypercalcaemia in these patients. Treatment with intravenous APD (10-15 mg daily until normalization of the serum calcium level) normalized serum calcium in 29 of 31 patients with hypercalcaemia due to advanced breast cancer. Survival in these 29 patients varied between 8 and 693 days (median 140 days) and 7 patients achieved a partial remission or stabilisation of disease during subsequent anti-tumor therapy. In 16 of the 29 patients in whom APD treatment was initially successful, hypercalcaemia recurred after a median period of 65 days. Eleven of these patients received a second course of APD, which was equally successful as the first in terms of percentage of patients with normalization of serum calcium, total dose of APD needed, and duration to normalization of serum calcium. Recurrent hypercalcaemia occurred significantly faster after the second successful APD course (median 17 days) than after the first (median 65 days). When only patients with progressive disease were taken into account, recurrence of hypercalcaemia usually occurred early, both after a first (median 23 days) and after a second successful APD course (median 17 days). Normalization of serum calcium occurred in 4 of 6 patients receiving a third APD course, in all 3 patients receiving a fourth, and in 1 of 2 patients receiving a fifth course. We conclude that with the use of APD, hypercalcaemia as the cause of death in patients with advanced breast cancer can be avoided or delayed, which offers better prospects for the palliative care of these women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689842
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  • 70
    Electronic Resource
    Electronic Resource
    New strategies in marrow purging for breast cancer patients receiving high-dose chemotherapy with autologous bone marrow transplantation (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. S19 
    Details
    ISSN: 1573-7217
    Keywords: amifostine ; autologous bone marrow transplantation (ABMT) ; breast cancer ; 4-hydroperoxycyclophoshamide (4-HC) ; marrow purging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High-dose chemotherapy and autologous bone marrow transplantation (ABMT) are commonly used to treat selected patients with high-risk breast cancer. A limitation of ABMT is that clonogenic cancer cells could be collected with the bone marrow and produce a relapse of disease when reinfused into patients. Purging the marrowex vivo may eliminate the tumor cells, but it can also delay engraftment. We employed two different purging methods whereby breast cancer cells were depleted without delaying engraftment. The addition of WR-2721 (amifostine) to 4-hydroperoxycyclophosphamide (4-HC) reduced the time to engraftment by 10 days compared with marrow purged with 4-HC alone (26 versus 37 days, respectively). The positive selection of CD34+ hematopoietic progenitors produced engraftment within 21 days. The use of granulocyte colony-stimulating factor (G-CSF) accelerated the engraftment time of CD34+ hematopoietic progenitors to 11 days.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668356
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  • 71
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    Application of peripheral blood progenitors to dose-intensive therapy of breast cancer (1993)
    Springer
    Breast cancer research and treatment 26 (1993), S. S25 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; high-dose chemotherapy ; peripheral blood progenitor cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dose-intensive therapy has been used with increasing frequency in the treatment of women with breast carcinoma. This therapy requires chemotherapeutic agents that exhibit a steep dose-response curve and that have myelosuppression as their primary dose-limiting toxicity. To hasten or to rescue hematologic function after dose-intensive therapy, a hematopoietic rescue is used. The source of this rescue has traditionally been autologous bone marrow cells. However, circulating peripheral blood progenitor cells can also reconstitute hematopoiesis after dose-intensive therapy. The only prerequisites are that hematologic recovery is at least comparable and that survival is not adversely affected by the source of the stem cell graft. Peripheral blood progenitors can be procured in sufficient numbers after priming or mobilization with chemotherapy and/or hematopoietic growth factors. Peripheral blood progenitors collected in this fashion have led to complete and sustained hematologic reconstitution in women with metastatic breast cancer involving the marrow. In addition, peripheral blood progenitors can be used to augment autologous bone marrow grafts, further hastening hematologic recovery after dose-intensive therapy. Future studies will examine the role of peripheral blood progenitor support of multiple doseintensive cycles in women with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668357
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  • 72
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    DNA ploidy, S-phase, and steroid receptors in more than 127,000 breast cancer patients (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 9-20 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; flow cytometry ; hormone receptors ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several potential prognostic factors are available today for patients with breast cancer, and many more are being identified and studied. To evaluate the clinical utility of these factors, it will be necessary to measure them on a large number of patients, and then follow these patients so that multivariate survival analyses can be performed. The Oncology Research Network was established in 1986 by the University of Texas Health Science Center at San Antonio and Nichols Institute Reference Laboratories in order to evaluate the clinical utility of new prognostic factors for patients with primary breast cancer. The first generation of prognostic factors included steroid receptors, along with DNA ploidy and S-phase fraction determined by flow cytometry. Currently, laboratory results have been obtained from more than 127,000 patients, and follow-up information is available on a subset of more than 25,000 of these patients. S-phase fraction was related to the ploidy status of the tumor. An increased incidence of aneuploidy and higher S-phase fractions were found in estrogen and progesterone receptor negative tumors, tumors from patients with positive axillary lymph nodes, tumors greater than 2 cm in diameter, and patients younger than 35 years of age. Preliminary survival analyses suggest that S-phase fraction and DNA ploidy, in combination with other prognostic factors, are powerful predictors of early disease relapse. The Oncology Research Network provides an important resource for examining the clinical significance of new laboratory assays and for expediting improvements in existing laboratory techniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666351
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    A case of intracystic carcinoma of the breast: the importance of measuring carcinoembryonic antigen in aspirated cystic fluid (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 41-44 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; intracystic carcinoma ; CEA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report a case of intracystic carcinoma of the breast in which a correct preoperative diagnosis was achieved on the basis of an increased level of carcinoembryonic antigen (CEA) in the aspirated cystic fluid. A 62-year-old woman was admitted with a 10 × 10 cm painful mass occupying the right breast. Ultrasonography revealed a cystic lesion with papillary projections arising from the cyst wall. Cytological examinations showed no malignant cells in the hemorrhagic aspirated fluid. However, the CEA level in the fluid was 5.5 times higher than the serum CEA level using a murine anti-CEA monoclonal antibody. The high level of CEA led to the preoperative diagnosis of intracystic carcinoma. Histological examinations confirmed the diagnosis of intracystic carcinoma after a modified radical mastectomy. Immunohistochemical staining by an anti-CEA monoclonal antibody elicited a strong positivity with diffuse intracytoplasmic distribution in the carcinoma cells, although heterogeneity of staining was observed. It is suggested that the measurement of the CEA value by anti-CEA monoclonal antibody in the aspirated fluid is easy, safe, and helpful for the definitive diagnosis of intracystic carcinoma of the breast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666354
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  • 74
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    Consensus review of the clinical utility of DNA cytometry in carcinoma of the breast (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 55-59 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA flow cytometry ; ploidy ; prognostic factors ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This is the consensus statement regarding the clinical utility of DNA cytometry in breast cancer from the DNA Cytometry Consensus Conference held in Prout's Neck, Maine, USA, on October 1–4, 1992. Guidelines for clinical DNA cytometry generated at that meeting also appear in this issue of Breast Cancer Research and Treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666357
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    Breast cancer risk: weaving facts into fabric (1993)
    Springer
    Breast cancer research and treatment 28 (1993), S. 91-96 
    Details
    ISSN: 1573-7217
    Keywords: anxiety ; breast cancer ; counseling ; estrogen replacement ; familial breast cancer ; histologic risk evaluation ; mammography ; molecular genetics ; risk assessment ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666421
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    The invasive and metastatic properties of hormone-independent but hormone-responsive variants of MCF-7 human breast cancer cells (1993)
    Springer
    Clinical & experimental metastasis 11 (1993), S. 15-26 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; estrogen-independent ; invasion ; metastasis ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously isolated a series of MCF-7 human breast cancer cell variants which no longer require estrogen-supplementation for tumor growth in nude mice (Clarkeet al. Proc Natl Acad Sci USA 86: 3649–3653, 1989). We now report that these hormone-independent and hormone-responsive variants (MIII, MCF7/LCC1) can invade locally from solid mammary fat pad tumors, and produce primary extensions on the surface of intraperitoneal structures including liver, pancreas, and diaphragm. Both lymphatic and hematogenous dissemination are observed, resulting in the establishing of pulmonary, bone, and renal metastases. The pattern of metastasis by MIII and MCF7/LCC1 cells closely resembles that frequently observed in breast cancer patients, and provides the first evidence of metastasis from MCF-7 cells growingin vivo without supplementary estrogen. The interexperimental incidence of metastases, and the time from cell inoculation to the appearance of metastatic disease are variable. The increased metastatic potential is not associated with an increase in either the level of laminin attachment, laminin receptor mRNA expression, or secreted type IV collagenolytic activity. We also did not detect a significant decrease in the steady-state mRNA levels of the metastasis inhibitor nm23 gene. However, when growing without estrogenin vitro, MCF7/LCC1 cells produce elevated levels of the estrogen-inducible cathepsin D enzyme.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00880062
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    The possible role of stromal cell stimulation in worsening the prognosis of a subset of patients with breast cancer (1993)
    Springer
    Clinical & experimental metastasis 11 (1993), S. 295-305 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; dormancy ; growth stimulation ; host stromal cells ; immunosuppression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: This review examines the evidence that a subset of patients with breast cancer have tumors that are stimulated to grow by host cells in the tumor stroma. The search for such a minority group was prompted by the following observations. Adjuvant chemotherapy which is immunosuppressive improves disease-free interval and survival, whereas non-specific immunostimulation worsens the prognosis. Intrinsic immune reactivity is associated with a poor prognosis. A subset of tumors with a bad prognosis has anaplastic cells, dermal lymphatic invasion and a moderate to intense lymphoplasmacytic stromal infiltrate. Evidence is reviewed that adjuvant chemotherapy may be beneficial by virtue of its immunosuppressive effects in addition to tumor kill of minimal residual disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00058049
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    The p185 erbB2 protein is localized on cell organelles involved in cell motility (1993)
    Springer
    Clinical & experimental metastasis 11 (1993), S. 453-461 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; c-erbB-2 ; motility ; neu ; oncogenes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: In a previous paper, we have shown that the c-erbB-2-encoded protein p185 erbB2 is localized on the brush border of the proximal tubule kidney cells. In invasive duct cell carcinomas, the labeling was most obvious on the villous plasma membrane protrusions. From these observations the hypothesis was raised that p185 erbB2 could play a role in motility. To test this hypothesis, we quantified its distribution on the microvilli and plasma membrane protrusions and on the straight parts of the cell membrane after immunoelectron microscopy. These findings were compared with the localization on p185 erbB2 overexpressing SK-BR-3 human breast cancer cells before and after stimulation of motility by treatment with conditioned medium from COLO-16 cells (CM), which is also able to induce chemotaxis of these cells in a Boyden chamber assay. In the invasive duct cell carcinomas, the number of gold particles was nine times higher at the plasma membrane protrusions than at the straight parts of the cell membrane. In untreated SK-BR-3 cells, p185 erbB2 was similarly concentrated on the membrane of small microvilli and plasma membrane protrusions. Treatment of SK-BR-3 cells with CM leads to cell spreading, enlargement of the microvilli, formation of pseudopodia and chemotaxis. Aggregation of p185 erbB2 at the plasma membrane protrusions and pseudopodia is observed on immunofluorescence light microscopy. The concentration of p185 erbB2 is several times higher on these membrane extensions than on the straight parts after immunogold labeling. It is concluded that p185 erbB2 is localized on cell organelles involved in motility, and it is suggested that the molecule plays a role in cell movement, providing the capacity of tumor cells to spread and metastasize.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00054936
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    Hypercalcemia in breast cancer (1993)
    Springer
    Clinical & experimental metastasis 11 (1993), S. 359-367 
    Details
    ISSN: 1573-7276
    Keywords: bone turnover ; breast cancer ; humoral factor ; humoral hypercalcemia of malignancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Hypercalcemia is relatively frequent in malignancy with or without osteolytic bone metastases. It is thought that neoplastic cells may secrete substances which not only stimulate osteoclastic activity but are also capable of modifying the absorption, excretion, and resorption of calcium and phosphate ions. Since 1987, we have studied 24 breast cancer patients with hypercalcemia (22 with bone metastases and two without). The group of 22 patients with bone metastases were divided into two subgroups. The first consisted of 10 patients with high serum levels of humoral factors, such as parathyroid hormone-related protein (PTHrP), and/or prostaglandin E2 (PGE2) and/or interleukin 1 (IL-1), and high levels of bone markers, such as alkaline phosphatase, bone Gla protein and urinary hydroxyproline. The second subgroup consisted of 12 patients with high levels of bone markers alone. Bone histologic analysis showed an osteoclastic activation surrounding metastatic tumor tissue in six out of 10 patients of the first subgroup, while an evident osteolysis caused by the tumor cells was noted in seven out of 12 patients of the second subgroup. The two patients without bone metastases showed normal biochemistry and bone histologic examination. The authors, having tried to explain the pathogenesis of hypercalcemia, emphasize the importance of humoral factors secreted by tumor cells as a direct or indirect cause of hypercalcemia. The origin of hypercalcemia remains unclear in two patients without bone metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00132979
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    Alcoholic beverage consumption and risk of breast cancer in Spain (1993)
    Springer
    Cancer causes & control 4 (1993), S. 345-353 
    Details
    ISSN: 1573-7225
    Keywords: Alcoholic beverage consumption ; breast cancer ; case-control studies ; nutrition ; Spain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The relation between alcoholic beverage consumption and risk of breast cancer was examined. We used data from a population-based, case-control study that included almost all incident cases occurring in five Spanish regions from February 1990 to July 1991. A total of 762 women between 18 and 75 years of age, with a histologically confirmed, first diagnosis of breast cancer, were compared with 988 control women. Alcoholic beverage intake was measured by an interviewer-administered, semiquantitative food-frequency questionnaire. We used ‘nondrinkers’ as the reference category and divided the remainder into four categories according to alcohol intake. The multiple logistic analyses included not only alcohol intake but also possible confounding factors such as total caloric intake, age, socioeconomic status, and reproductive and medical histories. Even at moderate levels of alcohol intake (less than 8 g/day), a 50 percent increase in risk of breast cancer was found. The trend across categories of intake was statistically significant for wine and distilled drinks, as well as total alcohol intake. Consumption of 20 g or more of alcohol per day was associated with a 70 percent elevation in breast cancer risk compared with that of nondrinkers (adjusted relative risk (RR)=1.7,95 percent confidence interval = 1.3–2.3). Although the magnitude of the RR observed in our study was modest, our findings provide further support for a positive association between alcohol consumption and risk of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00051337
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    Variations in the distribution of motor end-plates in the avian pectoralis (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 65-88 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Most avian muscles consist of serially arranged, overlapping fibers that do not extend the length of the muscle. This condition appears to be plesiomorphic with respect to diapsid reptiles. The presence of this serialfibered architecture is evidenced by bands of stained motor end-plates (meps) perpendicular to the columns of fibers and dividing each column into a series of “segments.” The avian pectoralis was chosen for a study of variation in the distribution of meps within a single muscle. We report the interspecific variation for 158 specimens in 63 species. We also use additional specimens to examine intraspecific variation.Setting aside hummingbirds, which have an unique and clearly derived condition, the number of mep bands along a column of fibers near the shoulder falls within a remarkably small range. The number of segments is not obviously related to phylogenetic relatedness or to any characteristic of flight or ecology and is only slightly related to size. The largest specimens do average more segments per column, but there are no trends among small to medium-sized species, suggesting that there is an upper limit to fiber length. However, the shape of the sternum and pattern of connective tissue in the pectoralis alleviate the need for additional fibers in many large birds. These findings suggest that the architecture of the avian pectoralis is subject to some as yet unexplained selection that stabilizes the number of myofibers and/or motor neurons. The findings provide few clues as to whether the significant factors are phylogenetic, functional, ontogenetic, or some combination of these. © 1993 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052150105
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    Masthead (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150201
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    Morphological and functional bases of durophagy in the queen triggerfish, Balistes vetula (Pisces, tetraodontiformes) (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 101-118 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Tetraodontiform fishes are characterized by jaws specialized for powerful biting and a diet dominated by hard-shelled prey. Strong biting by the oral jaws is an unusual feature among teleosts. We present a functional morphological analysis of the feeding mechanism of a representative tetraodontiform, Balistes vetula. As is typical for the order, long, sharp, strong teeth are mounted on the short, robust jaw bones of B. vetula. The neurocranium and suspensorium are enlarged and strengthened to serve as sites of attachment for the greatly hypertrophied adductor mandibulae muscles. Electromyographic recordings made from 11 cranial muscles during feeding revealed four distinct behaviors in the feeding repertoire of B. vetula. Suction is used effectively to capture soft prey and is associated with a motor pattern similar to that reported for many other teleosts. However, when feeding on hard prey, B. vetula directly bit the prey, exhibiting a motor pattern very different from that of suction feeding. During buccal manipulation, repeated cycles of jaw opening and closing (biting) were coupled with rapid movement of the prey in and out of the mouth. Muscle activity during buccal manipulation was similar to that seen during bite-captures. A blowing behavior was periodically employed during prey handling, as prey were forcefully “spit out” from the mouth, either to reposition them or to separate unwanted material from flesh. The motor pattern used during blowing was distinct from similar behaviors described for other fishes, indicating that this behaviors may be unique to tetraodontiforms. Thus B. vetula combines primitive behaviors and motor patterns (suction feeding and buccal manipulation) with specialized morphology (strong teeth, robust jaws, and hypertrophied adductor muscles) and a novel behavior (blowing) to exploit armored prey such as sea urchins molluscs, and crabs. © 1993 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052150202
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  • 84
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    Early development of the chick embryo (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 165-182 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ultrastructure of the early chick embryo was investigated, using scanning (SEM) and transmission electron microscopy (TEM). Eggs were obtained from the shell gland by injecting hens intravenously with a synthetic prostaglandin or arginine vasopressin. Embryos were examined during late cleavage (stages IV-VI, Eyal-Giladi and Kochav, '76), formation of the area pellucida (stages VII-XI), and formation of the hypoblast (stages X-XIV). SEM highlighted the reduction in cell number at the underside of the embryo during formation of the area pellucida although it became apparent that the thickness of the embryo is not reduced to a single layer of cells at stage X. In addition, blastomeres at the perimeter of embryos (stages V-VI) project filopodial extensions onto a smooth membrane that separates the sub-embryonic cavity from the yolk. During hypoblast formation, epiblast cells generate stellate projections at their basal aspect, thus providing a meshwork for the advancing secondary hypoblast cells. By stage XII the epiblast was one cell thick and reminiscent of a columnar epithelium when viewed transversely. Cells of the deep portion of the posterior marginal zone were distinguished morphologically in the stage XII embryo by their many cell surface projections and ruffled appearance. Blastomeres at the perimeter of stage V-VI embryos projected filopodial extensions onto a smooth membrane which separates the sub-embryonic cavity from the yolk. This membrane is presumed to be confluent with the cytolemma. Evidence is presented demonstrating the presence of intracellular membrane-bound droplets which are hypothesised to contain sub-embryonic fluid. © 1993 Wiley-Liss, Inc.
    Additional Material: 41 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150205
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    Land crabs with smooth lungs: Grapsidae, Gecarcinidae, and Sundathelphusidae ultrastructure and vasculature (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 245-260 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The highly terrestrial grapsids and gecarcinids and the amphibious sundathelphusids all have large, expanded branchial chambers. The lining of the branchial chambers is smooth and well vascularized, and it functions as a lung. The respiratory membrane and the cuticle lining the lung are extremely thin (200-350 nm). The blood vessels within the lung are formed from connective tissue cells supported by collagen fibres and lined by a basal lamina. The major vessels in the lung are embedded deep in the branchiostegite and lie just beneath the thick outer carapace. These vessels branch towards the respiratory membrane, where they eventually lose their connective tissue coverings to form thin, flattened lacunae directly below the respiratory epithelium. The lacunae (exchange sites) are bordered by specialized connective tissue cells, which either bear microvilli on their apical surface (fimbriated cells) or are very smooth. The respiratory circulation in the lung is very complex, with two portal systems present between the afferent and efferent systems, producing a total of three lacunal exchange beds. Portal systems increase the surface area available for gas exchange. The major distributing vessel in the lung is the branchiostegal vein, which runs along the inner margin of the branchiostegite. The main venous supplies come anteriorly from the infraorbital and ventral sinuses and posteriorly from the procardial sinus. The main collecting vessel is the pulmonary vein, which arises anteriorly and which runs around the ventral perimeter of the branchiostegite before emptying into the pericardial sinus. © 1993 Wiley-Liss, Inc.
    Additional Material: 25 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052150306
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    Naturally occurring diblastodermic eggs in the annual fish Cynolebias: Implications for developmental regulation and determination (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 301-312 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Annual fish development differs from that of other teleosts because a phase of blastomere dispersion-reaggregation spatially and temporally separates epiboly from embryogenesis. The fate of dispersed blastomeres was assessed in diblastodermic eggs of the annual fishes Cynolebias whitei and C. nigripinnis. In typical teleosts, blastomere determination and the events of primary embryonic induction occur prior to or during epiboly, so diblastodermic eggs produce partially or completely duplicated embryos. In the diblastodermic eggs of Cynolebias, the two blastoderms are completely separate from the one cell stage to the high blastula. Blastoderm fusion begins during midepiboly. By the end of epiboly, blastoderm fusion has been completed, and the deep, embryo-forming blastomeres of both blastoderms have completely dispersed and intermingled to form a single cell population. A typical annual fish dispersed blastomere phase ensues. Blastomeres reaggregate into a single mass, in which one embryo develops. When hatched, the young fish have no obvious structural or functional abnormalities. We suggest that the dispersed blastomeres of annual fish eggs are equivalent and that induction or determination takes place within the reaggregate. Alternatively, dispersed cells are partially determined but highly regulative, so that, when two populations fuse, the cells sort out according to tissue type and form a single embryo. In either instance, the formation of a single, normal embryo seems to corroborate the hypothesis that the dispersed cell phase of annual fishes is an adaptation that prevents environmentally induced developmental defects. © 1993 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052150309
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    Morphological analysis of tendinous structure in the American alligator jaw muscles (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 171-181 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In the American alligator, the jaw muscles show seven bundles of tendinous structure: cranial adductor tendon, mandibular adductor tendon, lamina anterior inferior, trap-shaped lamina lateralis, lamina intramandibularis, lamina posterior, and depressor mandibular tendon (originating from the musculus depressor mandibulae, m. pseudotemporalis, m. adductor mandibulae posterior, m. adductor mandibulae externus, m. intramandibularis, m. pterygoideus anterior, and m. pterygoideus posterior). These tendinous structures are composed of many collagen fibrils and elastic fibers; however, the distributions and sizes of the fibers in these tendinous components differ in comparison with those of other masticatory muscles. The differences of these properties reflect the kinetic forces or the stretch applied to each tendon by the muscle during jaw movements in spite of the simple tendon-muscle junctions. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052170206
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    The horizontal septum: Mechanisms of force transfer in locomotion of scombrid fishes (Scombridae, Perciformes) (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 183-204 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We describe the complex shapes of myomeres and myosepta in the mackerels and tunas (Scombridae: Teleostei), and we reveal the orientation of two major systems of collagen fibers in myosepta and horizontal septa with respect to points of attachment to skeleton and skin. Our goal is to identify the likely pathways of the transmission of muscle forces during locomotion. Our primary conclusions are (1) that the collagen fibers of myosepta, horizontal septa, and skin are the organs that transfer locomotor forces from the contraction of myomeres to the backbone and caudal fin during locomotion, and (2) that locomotor muscle pulls against a three-dimensional structure of tendons, septa, and skin that is kept in tension by the radial expansion of the contracting muscle. The main horizontal septum is formed by the convergence of myosepta and is likely to be the major transmitter of muscle force to the axial skeleton. The geometry of the myomeres, the position of red muscle, and particularly the geometric conformation of crossed-fiber arrays of collagen in the main horizontal septum suggest specific mechanisms for the transfer of muscle force to the backbone among scombrid fishes. Morphometrics and the construction of physical models help us to identify musculoskeletal mechanisms of locomotion, and we present two quantitative models of locomotor mechanics in fishes. © 1993 Wiley-Liss, Inc.
    Additional Material: 12 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052170207
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    Oviductal morphology and eggshell formation in the lizard, Sceloporus woodi (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 205-217 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Despite a great deal of work in recent years on the structure of reptilian eggshells, few studies have examined the structure and regulation of the female reproductive tract in the formation of eggshell components, and none have examined the entire process from ovulation to oviposition. In this study, we examined oviductal structure in the oviparous lizard, Sceloporus woodi, followed changes in oviductal structure during gravidity, and determined uterine function in the formation of eggshell components. The endometrial glands of the uterus produce the proteinaceous fibers of the eggshell membrane mainly during the first 24 hours following ovulation, and the fibers are secreted intact and subsequently wrapped around the in utero eggs. Eggshell fibers of different thicknesses are layered around each egg, ranging from an inner layer of thick fibers that gradually become thinner medially and finally forms an outer layer of densely packed particulate matter. These changes in the fibrous layer are reflected by the thickness and length of fibers released from the endometrial glands. Calcium deposition occurs from 3 days following ovulation through day 14 (oviposition) and is accompanied by cellular changes in the luminal epithelium suggestive of secretory activity. Deposition of the eggshell components within the uterus occurs on all eggs simultaneously, rather than sequentially. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052170208
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    Morphogenesis and ductal development of the prostatic complex of the guinea pig (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 219-227 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphogenesis of glandular architecture of the three lobes of prostate gland of the guinea pig, lateral, dorsal, and coagulating gland was studied from 35 days gestation to 90 postnatal days. Epithelial ductal tubules of various lobes of the gland were microdissected after treatment by collagenase and displayed two dimensionally. The number of ductal tips was counted, and the volume of the ductal network was quantified using a graphic tablet. The results show that the growth and ductal morphogenesis fall into two phases: prenatal and postnatal. The first outgrowth of prostatic buds begins at 35 days gestation (gestational length is 65 days). Ductal growth and branching continues over the next 15-20 days and by 55 days gestation, approximately 60%, 79%, and 71% of the adult number of ductal tips of the lateral and dorsal lobes and coagulating gland respectively, are formed. The figures increase to 89%, 84%, and 106%, respectively, by birth. There is little increase in number of ductal tips thereafter. Postnatal growth is accomplished mainly by elongation of existing ductal network with a little additional branching but with an increase in size (volume) of the tubules. Canalization of ductal tubules occurs prenatally in all lobes but postnatal functional cytodifferentiation takes a slightly different pace among them. Ductal morphogenesis of the guinea pig prostate gland differs significantly in time-course from that of the mouse in which ductal development occurs mainly postnatally. © 1993 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052170209
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    Masthead (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052170301
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  • 92
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    Structure of comblike teeth of the ayu sweetfish, Plecoglossus altivelis (Teleostei: Isospondyli): I. Denticles and tooth attachment (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 229-238 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The structure and tooth attachment of the comblike teeth and denticles of the ayu sweetfish, Plecoglossus altivelis, were examined by light and scanning electron microscopy. The denticle is composed of a spoonlike crown with a spine pointed anteriorly, a triangular plate in the cervical region, and a root that curves laterally and tapers off to a point. The root apex is fused with a long thin pedicle that turns abruptly anteriad toward the jaw bone. Planes of the spine, the spoonlike crown, the triangle plate and the root of the denticle are varied, and the denticle is twisted in the region of the triangle plane.The superficial layer of the dentine is homogeneously calcified and is considered to be enameloid, because some of the inner dentinal epithelial cells in the tooth germ are columnar and possess cellular processes at their apical ends. The dentine is fibrous and fine dentinal tubules are visible in dentine treated with sodium hydroxide and observed by scanning electron microscopy. The upper half of the root is surrounded by a dense layer of collagen fibers running parallel to the tooth axis, and the lower half is encompassed by interlaced collagen fibers. The lower part of the root is open on its lingual side. The pedicle is a long rod which is homogeneously calcified and enmeshed by interlaced collagen fibers, and it curves mediad as it nears the jaw bone. The pedicles are interposed between a layer of gelatinous connective tissue and the jaw bone and terminate on the periosteum. Comparative aspects of ayu tooth morphology are discussed. © 1993 Wiley-Liss, Inc.
    Additional Material: 15 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052170210
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  • 93
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    Effects of juvenile hormone analogues upon soldier differentiation in the termite Reticulitermes santonensis (Rhinotermitidae, Heterotermitinae) (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 239-261 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Under the influence of juvenile hormone analogues (JHAs), termite workers are induced to differentiate into soldiers. In Reticulitermes santonensis, such induced differentiation is often incomplete, resulting in intercaste production. The morphology of the structures most affected during differentiation was analyzed descriptively and biometrically in normal workers, presoldiers, and soldiers, and in experimental intercastes. We observed that intercastes form a morphological and biometrical continuum between workers and presoldiers (presoldier intercastes), and between presoldiers and soldiers (soldier intercastes). We also compared the biochemistry of the normal individuals and of the intercastes; in contrast to workers, the intercastes possess a frontal gland secretion which differs from those of the presoldiers and soldiers. Besides intercaste characterization, we consider the mode of action of JHAs in termite differentiation. © 1993 Wiley-Liss, Inc.
    Additional Material: 41 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052170211
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  • 94
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    Microtopography of Nippostrongylus brasiliensis (Nematoda: Heligmosomatidae): Free-living larval stages (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 217 (1993), S. 263-271 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Microtopographic features of the various growth stages of the three free-living larval stages of the rat hookworm Nippostrongylus brasiliensis (Nematoda) were surveyed by scanning electron microscopy. These worms have a rounded anterior end and an elongated tail. Cuticular annulations were observed along the body, which also bore two ribbon-like lateral alae. Two rings of six lip-like lappets were observed around the triradiate oral opening in all larval stages. The cephalic space contained two lateral amphidial pits. The excretory pore in the third anterior part was observed in a ventral view of the larvae. No deirids were observed. The anus with a crescent-shape opening was located posteriorly. Phasmidial apertures, only observed in the third-stage larvae, opened on the lateral alae in the tail region. © 1993 Wiley-Liss, Inc.
    Additional Material: 28 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052170302
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  • 95
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    Two different patterns of interrupted spermatogenesis in winter diapause and summer quiescence in the desert beetle, Omorgus freyi (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 218 (1993), S. 347-358 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Spermatogenesis discontinues during both adult reproductive diapause and quiescence in the flightless males of Omorgus freyi. During both types of dormancy, spermatogenesis discontinuity is a dynamic process involving an uninterrupted supply of primary spermatocytes that undergoes partial development and lyses before spermatozoa can be formed. Notwithstanding this common feature, the pattern of discontinuity differs between the two kinds of dormancy. During reproductive diapause, spermatozoa and late spermatids are the first cells that lyse; after diapause break, spermatozoa are produced anew. During quiescence, in contrast, the first indication of discontinuity is the degeneration of late primary spermatocytes; spermatozoa apparently remain intact for a while but eventually degenerate as well. Therefore, males returning to sexual activity after a short period of quiescence may still have spermatozoa capable of fertilization. However, following a long period of quiescence, spermatozoa will be absent and must be produced anew, as in postdiapausing males. The existence of two different patterns of spermatogenesis discontinuity may indicate that each is controlled differently by the endocrine system, in response to the different environmental conditions inducing quiescence or diapause. Dual control of discontinuity may contribute to the high reproductive potential of these flightless beetles, under unpredictable and extreme desert conditions. © 1993 Wiley-Liss, Inc.
    Additional Material: 18 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052180309
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  • 96
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    Masthead (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993) 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150101
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  • 97
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    Structure of recent and fossil mysid statoliths (Crustacea, Mysidacea) (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 31-49 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Statoliths of 61 Recent species representing all subfamilies of Mysidae were studied with special emphasis on internal structure. In addition 5 samples of fossil statoliths from Miocene deposits were examined. Species of Boreomysinae and Rhopalophthalminae show simple roughly spherical organic statoliths, with setae originating from the sensory cushion and anchored in the statolith with distal branches extending shortly below the surface. All other subfamilies possess mineralized statoliths of greater structural complexity, with differentiation in core and mantle, where each part may consist of up to three layers. Habitus is hemispherical to discoidal. External gross structures are dorsal tegmen, ventral fundus, and the ambitus forming the outer toroidal to semi-toroidal circumference. Setae penetrate the mantle through mineralic canals and insert on the surface of the core. As suggested by congeneric species of Schistomysis, there is no principal structural difference between statoliths mineralized with fluorite compared to vaterite. However, vaterite statoliths tend to be more often of moruloid appearance and are exceptional by showing a central conical hole (the hilum) or a central cavity in certain forms. These structures are typical of fossil calcite statoliths. In vaterite and fluorite statoliths, the mantle shows radially arranged (= spherulitic) crystal aggregates. Such arrangements are badly preserved in fossil calcite statoliths. In large extant statoliths, concentric structures, mainly in the form of superficial striation and/or concentric microstrata, are visible in coexistence with radial aggregates. Stratification is possibly due to stratified deposition of the nonmineralized gland product, while the spherulitic structure is indicative of subsequent radial growth of crystal aggregates. The structure of accessory fluorite statoliths in the statocyst of Mesopodopsis slabberi leads to the hypothesis that mantle material is formed by secretions of the caudal statocyst gland. After demineralization of fluorite, vaterite and calcite statoliths, an organic template remains showing most essential morphological features of the statolith. From this we conclude that the structure of the statolith is (almost) entirely matrix mediated. © 1993 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150103
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    An ultrastructural study of the dorsal lingual epithelium of the crab-eating frog, Rana cancrivora (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 89-100 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The amphibian tongue contains two types of papilla which are believed to function in gustation and in the secretion of salivary fluid. Scanning electron microscopy reveals that columnar, filiform papillae are compactly distributed over nearly the entire dorsal surface of the tongue of the frog, Rana cancrivora, and fungiform papillae are scattered among the filiform papillae. Microridges and microvilli are distributed on the epithelial cell surface of the extensive area of the filiform papillae. Light microscopy shows that the apex of each filiform papilla is composed of stratified columnar and/or cuboidal epithelium and its base is composed of simple columnar epithelium. Transmission electron microscopy reveals that most of the epithelium of the filiform papillae is composed of cells that contain numerous round electron-dense granules 1-3 μm in diameter. Cellular interdigitation is well developed between adjacent cells. On the free-surface of epithelial cells, microridges or microvilli are frequently seen. Between these granular cells, a small number of ciliated cells, mitochondria-rich cells and electron-lucent cells are inserted. In some cases, electron-dense granules are present in the ciliated cells. At higher magnification, the electron-dense granules appear to be covered with patterns of spots and tubules. Overall, the morphology and ultrastructure of the lingual epithelium of the three species of Rana that have been studied are quite similar, but they can be easily distinguished from those of Bufo japonicus. Therefore, it appears that lingual morphology is phylogenetically constrained among members of the predominantly freshwater genus Rana to produce uniformity of papillary structure and this morphology persists in Rana cancrivora despite the distinct saline environment in which it lives. © 1993 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150106
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  • 99
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    Pigment pattern formation in the larval salamander Ambystoma maculatum (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 151-163 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: As part of an ongoing comparative study of pigment patterns and their formation in embryos and larvae of ambystomatid salamanders, Ambystoma maculatum from two differnt populations, one in the northern (New York) and one in the central (Tennessee) United States, were investigated. Scanning electron microscopy was used to study early neural crest development. Light microscopy in combination with markers for the two pigment cell types (xanthophores and melanophores) made it possible to follow pigment cell migration before the pigment cells were fully differentiated. A bilateral pigment pattern consisting of two horizontal melanophore stripes surrounding an interstripe area populated by xanthophores formed in the larvae. In both populations, some variation was present in the form of a continuum ranging from clear horizontal stripes to extreme cases with a random pattern. Unlike the other ambystomatids that have been investigated, the neural crest cells in A. maculatum do not form aggregates and no vertical bars are formed. Instead, both the pattern and its formation are very similar to what has been reported for salamandrids. If pattern formation mechanisms can act as developmental constraints we would expect the A. maculatum pattern to be the primitive condition in the Ambystomatidae, using the Salamandridae as the outgroup. There is no strong support for this when aggregate formation is used as a character and mapped onto phylogenies for the group. The aggregate formation mechanism, and the pigment pattern that it leads to, have most likely been secondarily lost in A. maculatum. © 1993 Wiley-Liss, Inc.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150204
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  • 100
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    A morphologic study of the ductus of the epididymis of Sus domesticus (1993)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 215 (1993), S. 183-193 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The head, body, and tail regions of the epididymal duct (or caput, corpus, and cauda epididymis) in two healthy and sexually mature Sus domesticus males were examined by light microscopy and by scanning or transmission electron microscopy. The epididymal duct is lined with a pseudostratified epithelium with stereocilia and covered by a muscular-connective tissue sheath that is thickest in the tail region. Diameter of the epididymal duct and height of epididymal epithelium are maximal in the head region. Length of the sterocilia and spermatic density are higher in the head and body regions. Somatic cells are abundant in the tail region. The epididymal epithelium is made up of five cell types: basal cells, principal cells, clear cells, narrow cells, and basophilic cells. Abundant secretory units are observed in the supranuclear cytoplasm of columnar principal cells. Each mature secretory unit is constituted by electron-dense secretion granules covered by more than eight layers of cisternae of reticulum between which the mitochondria are intercalated. In the apical cytoplasm the isolated secretion granules become larger and less electron dense. The apical surface is covered by numerous sterocilia. Basal cells are pyramidal and less high than principal cells. The clear cells, arranged between the principal cells, are characterized by the presence of abundant vesicular elements and electron-lucid secretion granules, and by an apocrine secretory process. The narrow cells are characterized by their highly vacuolized cytoplasm. Intermediate cell typologies can be found among basal, principal, clear, and narrow cells, which could be four developmental stages of the same cell type. The basophilic cells are spheroidal and are found at different levels between the epithelial cells and in the connective tissue underlying the epithelium. © 1993 Wiley-Liss, Inc.
    Additional Material: 39 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052150206
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