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  • 1990-1994  (16,716)
  • 1970-1974  (7,119)
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  • General Chemistry  (17,937)
  • Life and Medical Sciences  (14,516)
  • breast cancer
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  • 1
    Electronic Resource
    Electronic Resource
    The relationship of p53 Protein and lymph node metastases in invasive breast cancer (1994)
    Springer
    Surgery today 24 (1994), S. 512-517 
    Details
    ISSN: 1436-2813
    Keywords: p53 protein ; breast cancer ; lymph node metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The p53 expression in invasive breast cancers from 106 patients was correlated with clinicopathological variables to ascertain its usefulness for estimating prognosis. The p53 expression was significantly associated with the number of axillary lymph node metastases and the presence of internal mammary lymph node metastases; however, it was not associated with age, menopausal status, histologic type, or tumor size. Although p53 expression was a significant prognostic factor according to univariate analysis, it did not appear to be an independent prognostic factor according to multivariate analysis. Thus, the prognostic power of p53 expression is likely to be weak and therefore probably of limited clinical value. Nevertheless, the number of patients in our study was small, and we believe that an investigation of a larger series of patients is indicated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01884570
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  • 2
    Electronic Resource
    Electronic Resource
    Reappraisal of internal mammary lymph node dissection in selected patients with invasive breast cancer (1994)
    Springer
    Surgery today 24 (1994), S. 795-802 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; extended radical mastectomy ; internal mammary lymph node ; multivariate analysis ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a new type of en bloc extended radical mastectomy (EXT) as a clinical trial in 118 patients from 1980 through 1985. A variety of conventional radical mastectomies (RDL) were also undertaken in 105 patients from 1973 through 1985. In this retrospective study, univariate and multivariate analyses were performed to compare the results of EXT and RDL. The univariate analysis showed that the 10-year survival rates for the EXT and the RDL groups were 86% ± 3.3% and 77% ± 4.2%, respectively (P = 0.073 with the Cox-Mantel test). For the subgroups stratified according to the status of axillary lymph node involvement, the EXT was significantly better in patients with one to three metastatic axillary lymph nodes (P = 0.016). The adjusted Cox regression analysis revealed that the favorable results of EXT were most encouraging in the patients with one to three metastatic axillary lymph nodes (P = 0.058). Therefore, it is suggested that an EXT may be more advantageous than RDL in selected patients with resectable invasive breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01636309
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  • 3
    Electronic Resource
    Electronic Resource
    The prognostic significance of epidermal growth factor receptor expression in breast cancer (1994)
    Springer
    Surgery today 24 (1994), S. 889-894 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; epidermal growth factor receptor ; prognosis ; lymph node metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The association between epidermal growth factor receptor (EGFR) expression, clinicopathological variables, silver-stained nuclear organizer region (Ag-NOR) counts, and patient survival was determined in 93 patients with operable breast cancer. The EGFR expression was found to be significantly associated with the presence and number of axillary lymph node metastases (P = 0.0429), but not with age, menopausal status, tumor size, histologic type or grade, or Ag-NOR counts. In a univariate analysis, a significant difference was also observed in the survival of patients stratified by tumor size (P = 0.0091), histologic grade (P = 0.0352), axillarly lymph node metastases (P = 0.0001), and EGFR expression (P = 0.0263). However, a multivariate analysis revealed that axillarly lymph node metastases was the only strong independent predictor ol'survival (P 〈 0.0001). When axillary lymph node metastases were excluded from the Cox model, the EGFR expression tended to be an independent prognostic factor (P = 0.0558). The results of this study thus indicate that the prognostic value of EGFR expression is limited because the EGFR expression is significantly associated with axillary lymph node metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01651004
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  • 4
    Electronic Resource
    Electronic Resource
    Changing practices in the surgical treatment of breast cancer in Japan: A nationwide survey by the Japanese Breast Cancer Society (1994)
    Springer
    Surgery today 24 (1994), S. 133-136 
    Details
    ISSN: 1436-2813
    Keywords: breast cancer ; national survey ; breast-conserving surgery ; geographic variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A nationwide survey in Japan of the patients with primary breast cancer from 1989 to 1991 revealed marked changes in the surgical treatment of the disease. During this period, there was a significant trend toward fewer instances of radical and extended radical mastectomies, and an increase in modified radical mastectomies and breast-conserving surgery. The percentage of breast-conserving surgery for the early-stage disease increased from 6.8% to 12.7%. Among the types of operations for breast-conserving surgery, quadrantectomy was used for 51.5% of the cases, while either a partial mastectomy or a subcutaneous mastectomy was used for 18.2% and 18.9%, respectively; a lumpectomy was performed in 10.9% of the cases. As for the proportion of patients receiving radiation therapy after breast-conserving surgery, 77% of those undergoing lumpectomy received radiation in contrast to only 43% of the patients undergoing quadrantectomy. According to the data from 1991, we also found that breast-conserving surgery was performed more often in larger cities and urban areas in Japan. As a result, we found that substantial changes in the treatment of localized breast cancer had taken place from 1989 to 1991. Regarding the details of breast-conserving surgery, however, some variation still remains in spite of the publication of numerous clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02473394
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  • 5
    Electronic Resource
    Electronic Resource
    The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer (1994)
    Springer
    Surgery today 24 (1994), S. 337-341 
    Details
    ISSN: 1436-2813
    Keywords: breast self-examination ; questionnaire survey ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P〈0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP〈0.01 andP〈0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P〈0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P〈0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02348564
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  • 6
    Electronic Resource
    Electronic Resource
    The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases (1994)
    Springer
    Surgery today 24 (1994), S. 215-220 
    Details
    ISSN: 1436-2813
    Keywords: parathyroid hormone-related protein ; breast cancer ; skeletal metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4133). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin-embeded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4133, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P 〈 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P 〈 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02032890
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  • 7
    Electronic Resource
    Electronic Resource
    How compliant is compliant? Evaluating adherence with breast self-exam positions (1994)
    Springer
    Journal of behavioral medicine 17 (1994), S. 523-534 
    Details
    ISSN: 1573-3521
    Keywords: breast self-examination ; compliance ; breast cancer ; positions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract The present study examined compliance with the three recommended breast self-examination (BSE) positions over a 6-month follow-up period. An ongoing behavioral measure that provided information about the type of exam performed during each BSE occasion was employed. Results indicated that adherence to all three position types was obtained in only 40% of the exams. Forty-two percent of exams were comprised of only one position, with the supine position being the most frequently practiced exam type. Implications of these results with regard to BSE research and current breast cancer screening recommendations are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01857924
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  • 8
    Electronic Resource
    Electronic Resource
    Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression (1994)
    Springer
    Glycoconjugate journal 1 (1994), S. 37-43 
    Details
    ISSN: 1573-4986
    Keywords: breast cancer ; fucose ; haptoglobin ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract There is increasing evidence for changes in fucosylation in cancer. Previously, we showed that the fucose-specific lectin,Lotus tetragonolobus, extracts an abnormal form of haptoglobin (Hp) from cancer sera. This study investigates the monosaccharide content of Hp obtained from women with ovarian and breast cancer at different stages of their disease. In both cancers, Hp fucose was low when the disease was benign or in remission and much higher when the disease was progressive. This occurred whether the data was expressed per mole of protein or per three mannose residues. Changes in other monosaccharides were minor compared with fucose. There were small increases in theN-acetylglucosamine and galactose content (per three mannoses) in ovarian cancer, suggesting that some glycan chains have increased branching. The latter was independent of disease activity which may be due to some indirect cause such as cytotoxic therapy or an inflammatory response. When ovarian cancer patients were in remission, the number of glycosylation sites on Hp was reduced. Hp isolated from patients with early, but not advanced breast cancer also appeared to have increased glycan branching. The increased fucosylated Hp may interfere with fucose-mediated adhesion reactions of cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00917467
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  • 9
    Electronic Resource
    Electronic Resource
    Phase II evaluation of mitoxantrone plus cis-platinum in patients with advanced breast cancer (1994)
    Springer
    Investigational new drugs 12 (1994), S. 129-132 
    Details
    ISSN: 1573-0646
    Keywords: cis-platinum ; mitoxantrone ; breast cancer ; phase I-II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The Southwest Oncology Group studied the response rate and toxicity of mitoxantrone (7.5 or 10 mg/m2 to 12.0 mg/m2) and cis-platinum (100 mg/m2) in 30 patients with advanced breast cancer as second-line therapy. There were 2 partial responses in 29 eligible patients. Toxicity was considerable, with 27 patients having grade 3 or 4 toxicity. Grade 3–4 toxicity included vomiting, thrombocytopenia, granulocytopenia, leukopenia and anemia. The combination of mitoxantrone plus cis-platinum has minimal activity as second-line therapy in metastatic breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00874442
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  • 10
    Electronic Resource
    Electronic Resource
    Phase I/II trial of dipyridamole, 5-fluorouracil, leukovorin, and mitoxantrone in metastatic breast cancer (1994)
    Springer
    Investigational new drugs 12 (1994), S. 283-287 
    Details
    ISSN: 1573-0646
    Keywords: breast cancer ; dipyridamole ; mitoxantrone ; 5-FU ; leukovorin ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m2 by mouth every 6 h (700 mg/m2/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m2 was given intravenously immediately prior to 5-FU 375 mg/ m2 intravenously on days 1–5. Mitoxantrone 6 mg/m2 was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1–2, 5-FU 375 mg/m2 days 1–2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873042
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  • 11
    Electronic Resource
    Electronic Resource
    Phase II trial of piroxantrone in metastatic breast cancer (1994)
    Springer
    Investigational new drugs 12 (1994), S. 333-336 
    Details
    ISSN: 1573-0646
    Keywords: piroxantrone ; oxantrazole ; anthrapyrazoles ; NSC-349174 ; Dup 942 ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m2 intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m2. We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873050
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  • 12
    Electronic Resource
    Electronic Resource
    1α,25-Dihydroxyvitamin D3 inhibits the invasive potential of human breast cancer cellsin vitro (1994)
    Springer
    Clinical & experimental metastasis 12 (1994), S. 195-202 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; cell proliferation ; invasion ; migration ; 1α ; 25-dihydroxyvitamin D3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using the Boyden chamber invasion assay, the effect of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] on the invasiveness of the highly invasive, oestrogen receptor-negative human breast cancer cell line MDA-MB-231 was examined. The MDA-MB-231 cells were shown to contain high-affinity receptors for 1α,25(OH)2D3 with a Kd of 1.5 × 10−11 M. When the cells were treated with 1α,25(OH)2D3 for 4 days before the assay was performed, a dose-dependent inhibition of their invasive potential was demonstrated. Fifty per cent inhibition of invasion was obtained with a concentration of 13 pM of 1α,25(OH)2D3. However, when the cells were treated for only 6 h during the assay, no inhibitory effect was seen. The process of migration was also affected by treatment with 1α,25(OH)2D3 for 4 days, although the inhibition was not of the same magnitude as seen for the invasion. Fifty per cent inhibition of migration occurred at a concentration of 3.2 nM of 1α,25(OH)2D3 (250 times higher than in the invasion assay). Inhibition of invasion and migration was not due to the known anti-proliferative effect of 1α,25(OH)2D3, as no growth reduction could be demonstrated with treatment up to 5 days. Based on the present investigation it can therefore be concluded that 1α,25(OH)2D3 is able to inhibit tumour cell invasiveness by a mechanism which is not exclusively based on its anti-proliferative and anti-migrative effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01753887
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  • 13
    Electronic Resource
    Electronic Resource
    Paraneoplastic sensorimotor neuropathy associated with breast cancer (1994)
    Springer
    Journal of neuro-oncology 21 (1994), S. 159-170 
    Details
    ISSN: 1573-7373
    Keywords: paraneoplastic syndrome ; sensorimotor neuropathy ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Paraneoplastic sensorimotor neuropathy occurs in association with many different types of cancer. The clinical findings are heterogeneous, and the pathogenesis is unknown. We have encountered 9 women with breast cancer and shared neurological features that suggest a distinct paraneoplastic syndrome. The syndrome is characterized by upper and lower extremity paresthesias and numbness, itching, muscle weakness and cramps, and in some, radicular symptoms and signs. Serum and CSF inflammatory changes suggested an immune pathogenesis but none had detectable antibodies directed at nervous system elements. Six patients presented with neuropathy 2 months to 8 years before the discovery of the breast cancer. In 7 the neoplastic disease was localized to the breast and axillary lymph nodes. The neurologic course was chronic in all, and while symptoms were annoying, disability was minimal until late. One improved transiently with plasmapheresis, and three had mild transient improvement with treatment of the cancer. Recognition of this paraneoplastic syndrome may forewarn the physician of an underlying breast malignancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01052900
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  • 14
    Electronic Resource
    Electronic Resource
    A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose (1994)
    Springer
    Cancer causes & control 5 (1994), S. 167-176 
    Details
    ISSN: 1573-7225
    Keywords: A-bomb survivors ; breast cancer ; ionizing radiation ; Japan ; reproductive history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the hombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor—age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births—conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early agefollowing exposure may be protective against radiation-related risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01830263
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  • 15
    Electronic Resource
    Electronic Resource
    The prognostic value of epidermal growth factor receptor (EGF-R) in primary breast cancer: Results of a 10 year follow-up study (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 73-83 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; estradiol receptor ; progesterone receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a study on 214 patients with primary breast cancer (median follow-up 8.5 yr, maximum follow-up 15 yr), EGF-R was negatively correlated to estrogen receptor and progesterone receptor, whereas no association was found with age, lymph node status, and tumor size. Initially, after a follow-up of 5 yr, there was a tendency to a significant association between EGF-R levels and tumor recurrence rate (p=0.08). Patients with tumors containing intermediate levels of EGF-R experienced a longer relapse-free survival (RFS) than did patients with tumors possessing lower or higher levels of EGF-R. This effect was most pronounced in the subgroup of patients with positive axillary lymph nodes. However, after 10 yr follow-up, this association appears to be lost (p=0.28) as shown in this update. A similar phenomenon was observed for the ER. While at 5 yr follow-up ER status had significant prognostic value (p=0.01), at 10 yr follow-up this significance also appears to be lost (p=0.40). However, tumor size, lymph node status, grade, and PgR status maintained significant prognostic value by univariate analysis. Based on 40 separate studies comprising 5232 patients, the mean percentage of EGF-R positivity reported in breast cancer is 45% (range 14–91%). Nine out of 15 different studies showed in some way a significant negative association between EGF-R and RFS by univariate analysis, and 2 others showed a tendency to such a relationship. Of 7 studies applying multivariate analysis, two demonstrated an independent prognostic value of EGF-R for RFS and two others a tendency to a significant correlation, whereas three did not. It may be concluded that EGF-R status has more or less prognostic value in patients with primary breast cancer, but the prognostic power decreases with longer follow-up. Of great clinical significance is the association of EGF-R with hormone resistance. Therefore EGF-R status can be used for selection of type of treatment. Finally, EGF-R might be useful as a target for new treatment modalities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666183
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  • 16
    Electronic Resource
    Electronic Resource
    Combined effects of 1,25-dihydroxyvitamin D3 and tamoxifen on the growth of MCF-7 and ZR-75-1 human breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 161-168 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; 1,25-dihydroxyvitamin D3 ; growth inhibition ; MCF-7 ; tamoxifen ; ZR-75-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we assessed the effect of combined treatment with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and tamoxifen (TAM) on the growth of estrogen-responsive (MCF-7) and estrogen-dependent (ZR-75-1) human breast cancer cells. Both basal and 17β-estradiol (17β-E2)-stimulated growth were studied. 1,25-(OH)2D3 (10−10 – 10−7 M) time- and dose-dependently inhibited basal growth of MCF-7 cells, with growth arrest at 10−7 M. Also, 17β-E2-stimulated growth of MCF-7 and ZR-75-1 cells was inhibited by 1,25-(OH)2D3 in a time- and dose-dependent manner. TAM inhibited 17β-E2-stimulated growth of both cell lines and at high concentration (10−6 M) it also inhibited basal growth of MCF-7 cells. 10−6 M TAM together with 1,25-(OH)2D3 resulted in a further inhibition of basal (MCF-7 cells) as well as 17β-E2-stimulated proliferation (MCF-7 and ZR-75-1 cells) compared to the inhibition by these agents alone. TAM in combination with 10−7 M 1,25-(OH)2D3 resulted in growth arrest of 17β-E2-stimulated growth of MCF-7 cells. The inhibition of basal and 17β-E2-stimulated growth of MCF-7 cells was additive at early time points (4 days), but less than additive at later time points (8–10 days). It was demonstrated that with co-treatment of MCF-7 cells an equipotent inhibition of basal growth could be reached with lower concentrations of 1,25-(OH)2D3, compared to treatment with 1,25-(OH)2D3 alone. Studies with low concentrations (〈 10−7 M) of TAM revealed a partial estrogenic effect, i.e. stimulation of MCF-7 proliferation in the absence of 17β-E2. This effect, which may resemble TAM-induced tumor flare, was completely prevented by co-treatment with a low concentration of 1,25-(OH)2D3 (10−9 M). Together, these results demonstrate the potent inhibition of breast cancer cell proliferation by 1,25-(OH)2D3 combined with TAM and indicate a potential benefit of combining these agents for the treatment of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665677
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  • 17
    Electronic Resource
    Electronic Resource
    Breast cancer: prognostic significance of c-erb-B2 and int-2 amplification compared with DNA ploidy, S-phase fraction, and conventional clinicopathological features (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 237-245 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prognosis ; gene amplification ; PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prognostic value of oncogene amplification and conventional clinicopathological features was determined in consecutive breast cancers detected during 5 months in 1975–1976 in 4 Swedish counties. Material was collected from 162 of the 179 patients and tumor size, nodal status, FSH, estrogen/progesterone receptor status, DNA ploidy and S-phase fraction determined. Tissues remaining from 80 patients were stored frozen until 1991, when amplification of the oncogenes c-erb-B2 and int-2 was determined. We show that c-erb-B2 amplification (but not int-2 amplification) and positive axillary nodal status show prognostic significance for both survival and relapse-free survival in univariate and multivariate analysis. The other examined factors showed no significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666477
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  • 18
    Electronic Resource
    Electronic Resource
    Demonstration of gene-amplification by PCR in archival paraffin-embedded breast cancer tissue (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 147-152 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; gene amplification ; PCR ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The polymerase chain reaction (PCR) is a powerful tool to examine genetic alterations in tumor samples. We describe a simple, rapid, nonisotopic PCR method to semi-quantitatively determine the number of gene copies in human formalin-fixed paraffin-embedded tissue. The procedure is exemplified by analysis of 15 years old breast cancer samples to determine the presence of amplification of c-erb-B2. The samples were obtained from routine specimens kept in pathological archives. Patients with amplified samples showed a poor prognosis, both for recurrences and death in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666058
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  • 19
    Electronic Resource
    Electronic Resource
    Analysis of a heterogeneous group of human breast carcinoma associated glycoproteins bearing the Tn determinant (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 139-152 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; carcinoma-associated glycoproteins ; monoclonal antibody 83D4 ; O-glycosylation ; Tn antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Tn determinant (GalNAcα-O-Ser/Thr) is expressed by about 90% of human carcinomas, but is cryptic in most normal human tissues. A murine monoclonal antibody (MAb) 83D4, developed following immunization with human breast carcinoma cells, reacts with a Tn-related epitope. In the present study we characterized the glycoprotein antigen identified by 83D4 in the human breast carcinoma cell line MCF-7. We further showed that the 83D4 antigenic determinant is masked in human milk fat globule membranes (HMFGM), and can be exposed upon mild m-periodate treatment after desialylation. Western-blot analysis resolved the 83D4 antigen from MCF-7 into two main components of 120–190 kD and 〉 500 kD respectively. Non equilibrium pH gradient electrophoresis/SDS PAGE revealed the acidic nature of the reactive glycoproteins (pI 4.43–4.70). 83D4 antigenic activity resolved by CsCl gradient ultracentrifugation layered on a wide range of densities (1.30–1.46 g/ml) including typical densities of mucin-like glycoproteins but also lower densities. The amino acid composition of the antigen, relatively rich in serine but poor in threonine and proline, confirmed the divergence from other mucin-like carcinoma-associated glycoproteins. Dicarboxylic amino acids were abundant, accounting in part for the acidic nature of the molecules. ELISA and Western-blot analysis of the subcellular fractions from MCF-7 cells revealed that the 83D4 antigen is mainly contained in plasma membranes (85%) from which it may be resolved into two broad bands (slow and fast migrating components). These results provide information on a group of breast carcinoma associated glycoproteins related to but different from typical mucins, and provide data on alteration of O-glycosylation in tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665765
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  • 20
    Electronic Resource
    Electronic Resource
    Ploidy and S-phase fractions (SPF) of primary breast cancers and their nodal metastases (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 197-202 
    Details
    ISSN: 1573-7217
    Keywords: DNA flow cytometry ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-one cases of primary breast cancers and their nodal metastases were examined with DNA flow cytometry. No differences were found between the stemline distributions in the primary tumors and nodal metastases. At both sites stemlines clustered around a DNA index of 1.0 (33–40% of cases) and 1.8. The mean S-phase fractions were 7.9 in primary tumors versus 5.6% in nodal metastases (p = 0.02); this difference was also observed if the analysis was restricted to cases with DNA aneuploidy at both sites (10.2 versus 7.6%, p = 0.04). Our results indicate that axillary nodal ploidy and proliferation reflect primary tumor characteristics rather than displaying changes associated with selection during the lymphatic metastatic process. Lymph nodes may have a suppressive effect on the proliferation of tumor cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665770
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  • 21
    Electronic Resource
    Electronic Resource
    The estrogen receptor from a tamoxifen stimulated MCF-7 tumor variant contains a point mutation in the ligand binding domain (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 129-138 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; tamoxifen ; drug resistance ; estrogen receptor mutant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nonsteroidal antiestrogen tamoxifen (TAM) is the most commonly used endocrine treatment for all stages of breast cancer in both pre- and postmenopausal women. However, the development of resistance to the drug is common, as most patients treated with TAM eventually experience a recurrence of tumor growth. One of the potential mechanisms of treatment failure is the acquisition by the tumor of the ability to respond to TAM as a stimulatory rather than inhibitory ligand. We (Gottardis and Jordan, Cancer Res 48: 5183-5187, 1988; Wolfet al., J Natl Cancer Inst 85: 806-812, 1993) and others (Osborneet al., Eur J Cancer Clin Oncol 23: 1189-1196, 1987; Osborneet al., J Natl Cancer Inst 83: 1477-1482, 1991) have extensively described the reproducible development of TAM stimulated growth in a laboratory model system using MCF-7 human breast cancer cells grown as solid tumors in athymic mice. In this paper we report on the isolation of an estrogen receptor (ER) from a TAM stimulated tumor (MCF-7/MT2) which contains a point mutation that causes a tyrosine for aspartate substitution at amino acid 351 in the ligand binding domain. The mutant appears to the major form of ER expressed by this tumor. We also report that only wild type ER was detected in three other TAM stimulated MCF-7 tumor variants, suggesting that multiple mechanisms are possible for the development of TAM stimulated growth. The implications of these findings are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689683
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  • 22
    Electronic Resource
    Electronic Resource
    Characterization of tamoxifen stimulated MCF-7 tumor variants grown in athymic mice (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 117-127 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; tamoxifen ; drug resistance ; MCF-7 sublives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The non-steroidal antiestrogen tamoxifen (TAM) is successfully used to treat all stages of breast cancer in both pre- and postmenopausal women. Unfortunately, most women treated with TAM eventually develop resistant tumor recurrences which require intervention with a second-line endocrine therapy, or cytotoxic chemotherapy if the recurrence is completely endocrine insensitive. There is evidence that some recurrences may in fact be TAM stimulated. MCF-7 human breast cancer cells grown as solid tumors in athymic mice chronically treated with TAM reproducibly develop a TAM stimulated phenotype (Osborneet al., Eur J Cancer Clin Oncol 23: 1189-1196, 1987; Gottardis and Jordan, Cancer Res 48: 5183-5187, 1988; Osborneet al., J Natl Cancer Inst 83: 1477-1482, 1991; Wolfet al., J Natl Cancer Inst 85: 806-812, 1993). Tumors of this type may provide a useful model for a subset of therapeutic failures in the clinic. Therefore, we have extensively studied this model in an attempt to define the mechanism or mechanisms leading to TAM stimulated growth. In this paper we describe the characteristics of 4 TAM stimulated MCF-7 tumor variants. All of these tumors are growth stimulated by TAM, but vary in their response to estradiol (E2) treatment, and grow poorly in placebo treated hosts. All tumor variants express estrogen receptor (ER) RNA and protein, which at the RNA level appear to be down regulated by TAM, and to a greater extent by E2. All tumors also express epidermal growth factor receptor (EGFR) RNA, which is down regulated by TAM, and further down regulated by E2. However, among the tumor variants analyzed, ER and EGFR levels appear to be inversely related. Further, despite the expression of ER by all 4 TAM stimulated tumor variants, E2 induction of progesterone receptor expression is very weak or entirely absent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689682
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  • 23
    Electronic Resource
    Electronic Resource
    Mechanisms of EGF receptor regulation in breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 227-236 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; gene expression ; hormone-indepence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Overexpression of the EGF receptor in breast cancer correlates with poor prognosis and failure on endocrine therapy for both ER−/EGFR+ and ER+/EGFR+ tumors, suggesting a role for EGFR in the progression to hormone independence. The identification of specific DNase I hypersensitive site patterns for the EGFR gene in ER+ vs. ER− cells implicates regions of the EGFR first intron in up-regulation of EGFR, while estrogen regulation studies indicate the involvement of a repressor(s) in the maintenance of low levels of EGFR. Based on these findings, a multi-step model is proposed for the progression of breast cancer from a hormone-dependent, ER+/EGFR- phenotype to an aggressive, hormone-independent, ER−/EGFR+ stage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666156
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  • 24
    Electronic Resource
    Electronic Resource
    Metabolism of breast cancer cells as revealed by non-invasive magnetic resonance spectroscopy studies (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 285-299 
    Details
    ISSN: 1573-7217
    Keywords: metabolism ; magnetic resonance spectroscopy ; phospholipid biosynthesis ; phosphorus-31 MRS ; proton MRS ; carbon-13 MRS ; hormonal effects ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The basis for the use of nuclear magnetic resonance (NMR) spectroscopy as a tool to study the metabolism of breast cancer cells is described. The differences between proton (1H), carbon (13C), and phosphorus (31P) NMR methods is explained, and the techniques of cell extracts, cell suspensions and perfusion methods for cells are detailed. In order to perfuse cells they are preferably trapped in a gel matrix, either in the form of a thread or a bead. The gel must have appropriate properties that enables efficient oxygenation and availability of nutrients and drugs. The metabolic effects of perfusion of breast cancer cells with nutrients, drugs, and hormones are reported, and the clinical relevance of these results and methods are outlined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666161
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  • 25
    Electronic Resource
    Electronic Resource
    Thymidine labeling index and Ki-67 growth fraction in breast cancer: Comparison and correlation with prognosis (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 165-175 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prognosis ; growth fraction ; Ki-67 ; TLI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ determination of proliferative activity was performed on 184 consecutive primary invasive breast cancers. Methods used were monoclonal antibody Ki-67 in immunohistochemistry and thymidine labeling index. Tumor proliferation correlated between both methods (p = 0.0001). For thymidine labeling index and Ki-67, respectively, significant correlations existed with histologic tumour grade and steroid hormone receptors (Tumor grade: TLIp = 0.0001; Ki-67 p = 0.0001. ER-ICA: TLI = 0.0001; Ki-67 p = 0.014. PgR-ICA: TLIp = 0.0001; Ki-67 p = 0.0008). For thymidine labeling index a significant correlation was demonstrated for overall survival (p = 0.001) and recurrence free survival (p = 0.01). No statistical significance was observed for clinical outcome and Ki-67 (overall survival p = 0.18; recurrence free survival p = 0.1). None of the factors, TLI or Ki-67, was an independent prognostic factor as demonstrated by multivariate analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665767
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  • 26
    Electronic Resource
    Electronic Resource
    The type I growth factor receptors in human breast cancer (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 3-9 
    Details
    ISSN: 1573-7217
    Keywords: growth factors ; receptors ; tyrosine kinase ; breast cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The type 1 family of growth factor receptors includes the EGFR, c-erbB2, c-erbB3, and c-erbB4. All four members of the family are expressed in breast cancer. The EGFR gene and more frequently the c-erbB2 gene are amplified in a proportion of cases. In addition to increased expression as a result of gene amplification, overexpression of perhaps all of the receptors also appears to occur, probably as a result of increased mRNA transcription. Overexpression may have prognostic value and may predict response to current therapies. Finally these GFR proteins represent targets for new types of chemotherapeutic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666177
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  • 27
    Electronic Resource
    Electronic Resource
    Role of epidermal growth factor receptor expression in primary breast cancer: results of a biochemical study and an immunocytochemical study (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 51-58 
    Details
    ISSN: 1573-7217
    Keywords: epidermal growth factor receptor ; prognostic factor ; c-erbB-2 ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have conducted two series of studies, a biochemical study and an immunocytochemical study, to investigate the role of epidermal growth factor receptor (EGFR) expression in primary breast cancer patients. In the biochemical study, a consecutive 115 patients were included and EGFR was measured by a competitive binding assay with multipoint Scatchard analysis. In the immunocytochemical study comprising 126 patients, EGFR status was determined by immunostaining with anti-EGFR antibody EGFR1. Several agreements were found from these two studies. EGFR status was inversely correlated with estrogen receptor (ER) status. No significant correlation was found between EGFR status and tumor size, nodal metastases, or the expression of c-erbB-2 protein. Ki-67 immunoreactivity, a cellular proliferation marker, was enhanced in EGFR positive tumors over EGFR negative tumors, suggesting a linkage of EGFR expression to cellular proliferative activity. Post-operative follow up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients, particularly in node-positive patients. Multivariate analysis demonstrated a significance of EGFR status as an independent prognostic indicator in primary breast cancer. The group expressing EGFR and c-erbB-2 protein indicated a particularly high risk for relapse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666181
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  • 28
    Electronic Resource
    Electronic Resource
    Epidermal growth factor receptor expression in breast cancer: Association with response to endocrine therapy (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 117-125 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; epidermal growth factor receptor ; estrogen receptor ; Ki67 ; c-erbB-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF-R, ER, Ki67, and c-erbB-2 product. All patients received assessable endocrine therapy following disease progression. Significant associations were observed between EGF-R and ER (inverse) and Ki67 (direct). No association was observed between EGF-R and the c-erbB-2 product. EGF-R expression was significantly associated with the loss of endocrine sensitivity in breast cancer. This was observed in both ER positive and negative disease. In ER positive breast cancers, EGF-R expression had no significant influence on the quality of tumour remissions. Further sub-classification of the ER/EGF-R data by Ki67 immunostaining showed that in ER+/EGF-R- disease, increasing proportions of Ki67 positive cells were associated with a decline in the numbers of women experiencing good quality tumour remissions. A similar trend was also observed in ER+/EGF-R+ tumours. The presence of c-erbB-2 protein product did not influence endocrine sensitivity in any of the ER/EGF-R sub-groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666187
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  • 29
    Electronic Resource
    Electronic Resource
    Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in the rat (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 203-217 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; dehydroepiandrosterone ; DHEA ; intracrinology ; prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The concentration of serum dehydroepiandrosterone sulfate (DHEA-S) and DHEA decreases markedly during aging, and low circulating levels of DHEA have been associated with a higher incidence of breast cancer in women. Using 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat as model, we have studied the effect of increasing serum levels of DHEA released from Silastic implants on the incidence of these tumors in the rat. Treatment with increasing doses of DHEA leading to serum DHEA levels comparable to those observed in normal adult women (7.1 ± 0.6 nM and 17.5 ± 1.1 nM) caused a progressive inhibition of tumor development from 68% bearing tumors in control animals to 22% and 11%, respectively. The average tumor area per rat decreased from 2.81 cm2 in intact control animals to 0.96 and 0.09 cm2 in the groups treated with the same doses of DHEA, respectively. The present data indicate that circulating levels of DHEA similar to those found in normal adult premenopausal women exert a potent inhibitory effect on the development of DMBA-induced mammary tumors in the rat, thus suggesting the possibility of a new and more physiological approach for the prevention of breast cancer in women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665681
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  • 30
    Electronic Resource
    Electronic Resource
    Prognostic relevance of transforming growth factor alpha (TGF-α) and tumor necrosis factor alpha (TNF-α) detected in breast cancer tissues by immunohistochemistry (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 229-235 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; TGF-α ; TNF-α ; monoclonal antibody ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The function of different growth factors in the development and progression of malignant tumors and the role of cytotoxic cytokines in the host response generated against neoplasms have been recently studied. Anti-TGF-α and anti-TNF-α monoclonal antibody families have been developed and characterized previously by our laboratory. Libraries of anti-TGF-α and anti-TNF-α monoclonal antibodies were selected for equal immunoreactivity both in native (frozen) and in formaldehyde fixed, paraffin embedded histological sections. No differences were found between native and fixed samples demonstrated in 10 cases in the present prospective study. Retrospective investigation was performed in 35 histopathological specimens of breast cancer patients detailed clinically and observed during 5 years after the surgical treatment. Correlation between TGF-α and/or TNF-α expression and clinical staging - TNM score, lymph node metastasis, tumor recurrence and survival time - was analyzed. According to our present study, the TGF-α positive patients had worse clinical prognosis than the TNF-α positive and double positive cases during long term observation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666476
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  • 31
    Electronic Resource
    Electronic Resource
    Results of chemotherapy using ifosfamide with doxorubicin in advanced breast cancer (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 271-277 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; doxorubicin ; chemotherapy ; ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666481
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  • 32
    Electronic Resource
    Electronic Resource
    Estradiol control of ornithine decarboxylase mRNA, enzyme activity, and polyamine levels in MCF-7 breast cancer cells: therapeutic implications (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 189-201 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ornithine decarboxylase ; polyamines ; estradiol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that natural polyamines - putrescine, spermidine, and spermine - play a key role in the mechanism of action of estrogens in breast cancer. Ornithine decarboxylase (ODC) is the first enzyme of the polyamine biosynthetic pathway. To examine estrogenic regulation of polyamine biosynthesis in breast cancer, we measured ODC mRNA, ODC activity, and polyamine levels in G1 synchronized MCF-7 cells. ODC mRNA and activity increased four-fold over that of cells in G1 phase between 8 to 16 h after the addition of estradiol. Polyamine levels showed a sharp increase by 8 h after the addition of estradiol and decreased by 12 h. We further examined whether synthetic homologs of putrescine or spermidine could replace natural polyamines in supporting MCF-7 cell growth. Treatment of MCF-7 cells with 1 mM difluoromethylornithine (DFMO), an inhibitor of ODC, suppressed putrescine, spermidine, and spermine levels by 74, 78, and 10%, respectively, within 48 h. Cells treated with DFMO for 48 h were supplemented with either putrescine or its homologs or spermidine or its homologs. Diaminopropane, diaminobutane (putrescine), and diaminopentane were capable of fully or partially reversing the growth inhibitory effects of DFMO, whereas diaminoethane had no significant effect. Among a series of triamines, H2N(CH2)nNH(CH2)3NH2 (where n = 2 to 8; abbreviated as APn n = 4 for spermidine, or AP4), spermidine was most effective in reversing the effects of DFMO, whereas compounds with shorter or longer methylene bridging regions were less effective. AP8 was ineffective in reversing the growth inhibitory effects of DFMO. At 10 µM concentration, AP8 also inhibited DNA synthesis by 66%, as measured by [3H]-thymidine incorporation. These data show that MCF-7 cells have a strong requirement for polyamines for their growth and that estradiol stimulates the polyamine cascade by inducing the ODC mRNA level. Our results also suggest that polyamine homologs such as AP8 might be potentially useful in breast cancer therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665680
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  • 33
    Electronic Resource
    Electronic Resource
    Effect of two 4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 127-132 
    Details
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; breast cancer ; growth factors ; hormonal treatment ; insulin-like growth factor I ; postmenopause
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A number of endocrine treatments for advanced breast cancer seem to affect serum insulin-like growth factor I (IGF-I). The aim of our study was to investigate IGF-I levels in 33 postmenopausal patients with metastatic disease receiving the selective aromatase inhibitor 4-hydroxyandrostenedione: 250 mg (16 patients) or 500 mg (17 patients) i.m. fortnightly. Blood samples were collected before, and at one month and 3 months after the beginning of treatment for radioimmunoassay determinations. The median patient age was 56 and 60 years in the 250 and 500 mg groups respectively. Most patients had a disease free interval ≥ 2 years and were oestrogen receptor positive. Objective responses were obtained in 3 patients (complete response, 1) in the 250 mg group, and in 7 patients (complete response, 3) in the 500 mg group. No significant IGF-I variations were seen in the 250 mg group, whereas a significant increase after 3 months (181.57 ± 84.78 ng/mlversus 272.47 ± 213.22 ng/ml, p = 0.0032) was observed in the 500 mg group. No IGF-I variations were seen between responsive and unresponsive patients in either treatment group. Our results in the 500 mg group are close to those obtained with aminoglutethimide and seem to agree with the hypothesis of an oestrogen-induced suppression of IGF-I circulating levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666055
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  • 34
    Electronic Resource
    Electronic Resource
    Relationship of serum and tumor levels of iron and iron-binding proteins to lymphocyte immunity against tumor antigen in breast cancer patients (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 305-309 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunity ; tumor antigen ; ferritin ; iron ; transferrin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fifty-two breast cancer patients were evaluated for levels of several molecules related to iron metabolism including determining their tumor tissue and serum ferritin levels, serum transferrin levels, and serum iron levels. In addition the patients' lymphocyte immunity against autologous tumor antigen was investigated. Forty percent (21 of 52) of the patients had lymphocyte immunity against tumor antigen. Iron metabolism molecules were expressed in abnormal quantities in some breast cancer patients: 27% (13 of 49) had elevated tumor tissue ferritin levels, 4% (2 of 49) had abnormally high serum ferritin, 10% (5 of 49) had abnormally low serum transferrin levels, and 43% (21 of 49) had depressed serum iron levels. None of these abnormalities in iron metabolism are associated with tumor immunity. These iron metabolism molecules may be indicative of rates of cell proliferation or may influence growth of breast cancer cells, but do not appear to influence host lymphocyte immunity against tumor associated antigens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665972
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  • 35
    Electronic Resource
    Electronic Resource
    Differentiation state and invasiveness of human breast cancer cell lines (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 325-335 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; vimentin ; invasion ; integrins ; cadherins ; epithelial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and β1 and β4 integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47DCO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666165
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  • 36
    Electronic Resource
    Electronic Resource
    The p53 tumor suppressor gene in breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 39-47 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; p53 gene ; p53 protein ; prognosis ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alterations of the p53 tumor suppressor gene are the most common genetic changes found so far in breast cancer, suggesting that the gene plays a central role in the development of the disease. p53 functions as a negative regulator of cell growth, and alterations in the gene lead to loss of this negative growth regulation and more rapid cell proliferation. A number of independent groups using different methods of detection have shown that p53 alterations are associated with more aggressive tumor biologic factors and a poorer prognosis in breast cancer patients. Because of its possible role in the regulation of apoptosis and response to DNA damage, p53 status could also be a predictive marker for response to hormonal or chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666204
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  • 37
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    Electronic Resource
    Flow cytometry: Potential utility in monitoring drug effects in breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 57-65 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; drug resistance ; flow cytometry ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Flow cytometric analysis of DNA ploidy and S-phase fraction are well recognized prognostic indicators in breast cancer. The present paper deals with the widening of the applications of flow cytometry to monitoring the effectiveness of antiestrogen therapy, detecting clonal selection and emergence of drug resistance, and monitoring chemosensitizing properties of drugs. Antiestrogen activity can be studied by DNA flow cytometry to address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance. Patient plasma specimens containing various concentrations of triphenylethylenes can be monitored for drug-induced effects using cell cycle measurements and correlated toin vivo drug levels. DNA flow cytometry has also been instrumental in the study of the effects of prolonged low-dose (0.5 µM for 〉 100 days) tamoxifen treatment on human estrogen receptor negative MDA-MB-231 cells, where it was shown that tamoxifen may significantly alter cell cycle kinetics and tumorigenicity of these cells, selecting a new, more aggressive, and rapidly growing clone. Lastly, it has been shown that the chemosensitizing properties of another triphenylethylene antiestrogen, toremifene, on estrogen receptor negative, multidrug resistant MDA-MB-231-A1 human breast cancer cells can be studied using flow cytometric analysis. Toremifene (and its metabolites N-desmethyltoremifene and toremifene IV) are able to “resensitize” MDA-MB-231-A1 cells to vinblastine and doxorubicin, as reflected in a marked shift of cells to G2/M phase of the cell cycle. Flow cytometry is a widely available technique that might be applied clinically to monitor, at the cellular level, drug effects on tumors, including the modulators of drug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666206
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  • 38
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    Electronic Resource
    Osteolytic bone metastasis in breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 73-84 
    Details
    ISSN: 1573-7217
    Keywords: bisphosphonates ; bone resorption ; breast cancer ; cadherins ; matrix metalloproteinases ; osteoclasts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metastasis of breast cancer cells to bone consists of multiple sequential steps. To accomplish the process of metastasis to bone, breast cancer cells are required to intrinsically possess or acquire the capacities that are necessary for them to proliferate, invade, migrate, survive, and ultimately arrest in bone. These capacities are essential for any cancer cells to develop distant metastases in organs such as lungs and liver as well as bone. Once breast cancer cells arrest in bone, bone is a storehouse of a variety of cytokines and growth factors and thus provides an extremely fertile environment for the cells to grow. However, breast cancer cells are unable to progress in bone unless they destroy bone with the assistance of bone-resorbing osteoclasts. Thus, the capacity of breast cancer cells to collaborate with osteoclasts is likely to be specific and is likely critical for them to cause osteolytic bone metastases. Evidence to support the concept that there is an intimate relationship between breast cancer cells and osteoclasts is described using anin vivo bone metastasis model in which human breast cancer cells are inoculated into the left ventricle of nude mice. The roles of cell adhesion molecules including cadherins and laminin and matrix metalloproteinases in the development of osteolytic bone metastases by breast cancer are also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666208
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  • 39
    Electronic Resource
    Electronic Resource
    Targeting the EGF receptor in breast cancer treatment (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 97-103 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; immunotoxins ; ligand fusion toxins ; targeted therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunotoxins are a relatively new class of cytotoxic agents consisting of a catalytic toxin linked to an appropriate targeting ligand. The ligand directs the toxin to the surface of a tumor cell, whereupon the toxin enters the cell and catalytically inactivates the ribosome, thus disrupting protein synthesis and effecting cell death. Monoclonal antibodies (or their fragments) have been most commonly used to carry chemically conjugated toxins to proteins or antigens overexposed on the tumor cell surface, but specific ligands for tumor cell surface receptors could also provide effective targeting. The receptor for epidermal growth factor (EGFR) is overexpressed primarily in poor prognosis breast cancers that do not respond well to traditional therapies. Because EGFR is frequently overexpressed in breast cancer tissue and is associated with a poor prognosis, it is an attractive target for antitumor therapy. DAB 389 EGF is an EGFR specific fusion toxin produced with recombinant DNA techniques consisting of sequences for the enzymatically active and membrane translocation domains of diphtheria toxin plus sequences for human epidermal growth factor. DAB 389 EGF is a potent, EGFR specific, cytotoxic agent which rapidly inhibits protein synthesis by a mechanism of action similar to that of diphtheria itself. Preclinical studies in the laboratory and in animals now suggest the feasibility of investigating such an agent in the targeted therapy of patients with human breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666210
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  • 40
    Electronic Resource
    Electronic Resource
    Survival analysis of censored data: Neural network analysis detection of complex interactions between variables (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 113-118 
    Details
    ISSN: 1573-7217
    Keywords: axillary nodal status ; breast cancer ; neural networks ; prognostic markers ; staging ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neural networks can be used as pattern recognition systems in complex data sets. We are exploring their utility in performing survival analysis to predict time to relapse or death. This technique has the potential to find easily some types of very complex interactions in data that would not be easily recognized by conventional statistical methods. In this paper we demonstrate that there are several ways neural networks can be used to find three-way interactions among variables. Thus, in data sets where such complex interactions exist, neural networks may find utility in detecting such interactions and in helping to produce predictive models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666212
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  • 41
    Electronic Resource
    Electronic Resource
    An alternative approach for treatment of breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 319-325 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; computer modeling ; kinetics ; therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since adjuvant chemotherapy and hormonal therapy generally extend disease free survival in breast cancer rather than provide a cure, we have examined the current breast cancer paradigm. Heterogeneity is a fundamental characteristic of breast cancer tissue and a well recognized aspect of the disease. There are variations in natural history, histopathology, biochemistry and endocrinology, and molecular biology of cancer tissues and cells within the tissues. A variety of data indicate that growth kinetics are also variable, not only from tumor to tumor, but also during the natural history of an individual's tumor. To better understand kinetic heterogeneity, a stochastic numeric computer model of the natural history of breast cancer has been developed. To be consistent with inter- and intratumor kinetic heterogeneity and with late relapse, the model predicts that tumors grow in an irregular fashion with alternating periods of growth and periods of dormancy rather than the generally accepted modified exponential, or Gompertzian fashion. The prediction of irregular growth has been compared to data relevant to growth characteristics of human breast cancer. Much data support the concept of irregular kinetics and temporary dormancy rather than steady, Gompertzian growth of human breast cancer. Thus, in addition to drug resistance, kinetic heterogeneity may help explain the limited impact that traditional chemotherapeutic treatment has had on mortality from breast cancer. Although the mechanisms underlying irregular growth need to be better understood, non-Gompertzian growth kinetics indicates that there may be alternative approaches for breast cancer treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666009
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  • 42
    Electronic Resource
    Electronic Resource
    Antiestrogen action and growth factor regulation (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 61-71 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; endometrium ; growth factors ; IGFs ; TGFs ; tamoxifen ; uterine cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The basis of the anti-proliferative action of antiestrogens is generally considered to be their ability to inhibit estrogen induced growth pathways by competitively inhibiting the binding of estrogen to the estrogen receptor. Recent data suggest that this may not be the entire story. Moreover, the cascade of events responsible for inhibition of mitogenesis after an initial interaction with the estrogen receptor is poorly understood. Multiple growth factor pathways operate in both normal and neoplastic estrogen/antiestrogen target tissues. While it is unlikely that any single pathway is pivotal, interactions of estrogen and/or antiestrogens with some of these pathways have been implicated in their proliferative effects. The exact molecular mechanisms remain unclear but autocrine, paracrine/juxtacrine, intracrine, and endocrine mediators or various combinations of them are likely to be involvedin vivo. Super-imposed on this is the possibility that ‘cross-talk’ between intracellular signaling pathways may also be involved. Elucidation of such molecular mechanisms will be important with respect to design of novel antiestrogenic/antimitogenic drugs and alternative treatment strategies for both breast and uterine cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689677
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  • 43
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    Electronic Resource
    Translational research in the San Antonio breast cancer SPORE (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 1-4 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; drug resistance ; growth factors ; heat shock proteins ; imaging ; premalignant disease ; prognostic factors ; tumor suppressor genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666200
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  • 44
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    Electronic Resource
    A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 59-71 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; immunocytochemistry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands. In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p=0.073) and with p53 expression (p=0.06); ii) EGFR is a significant indicator for recurrence (p〈0.01 and odds ratio of 2.82) but not for death (p=0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test=26.40; p〈0.01), c-erbB-2 protein and p53 mutant protein expression (likelihood ratio test= 5.94; p=0.05), cathepsin D (likelihood ratio test= 9.78; p〈0.01), and nodal status (likelihood ratio test= 7.32; p〈0.01) are significant and independent prognostic factors in early-stage breast carcinoma. This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666182
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  • 45
    Electronic Resource
    Electronic Resource
    S-phase determination of immunoselected cytokeratin-containing breast cancer cells improves the prediction of recurrence (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 179-187 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CAM 5.2 antibody ; cytokeratin ; flow cytometry ; prognosis ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Estimation of S-phase fraction in breast carcinomas with single parameter flow cytometry may include errors due to dilution of cancer cells by host cells. Use of tissue specific markers may to some extent correct for the effect of dilution. S-phase fraction was estimated by flow cytometry with and without immunoselection in 80 DNA-euploid breast carcinomas in stage I-II. The tumor tissue was mechanically disintegrated and fixed in ethanol. A primary antibody, specific for cytokeratins 8 and 18, was added before incubation with the secondary FITC-conjugated antibody. S-phase fraction was calculated for both the gated (cytokeratin-positive) and the ungated cell population. An increasing proportion of tetraploid cells compared to diploid cells was found when the immunoselection method was used. The gated population tended to have a higher S-phase fraction than the ungated population. In univariate analysis S-phase fraction estimated from both ungated and gated cell populations yielded significant information for predicting recurrence when stratified for tumor size and nodal status. In bivariate analysis S-phase fraction of the gated population contributed prognostic information in addition to S-phase fraction of the ungated population when both variables were included in the analysis. Our conclusion is that S-phase fraction calculated from cytokeratin-positive cells provides prognostic information in addition to ungated S-phase values in DNA euploid breast carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665679
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  • 46
    Electronic Resource
    Electronic Resource
    Lack of prognostic value of epidermal growth factor receptor in a series of 229 T1/T2, N0/N1 breast cancers, with well defined prognostic parameters (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 265-270 
    Details
    ISSN: 1573-7217
    Keywords: epidermal growth factor receptor ; breast cancer ; prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prognostic value of epidermal growth factor receptor (EGF-R) was prospectively assessed in a series of 229 clinical T1-T2, N0-N1 breast carcinomas diagnosed between May 1987 and October 1989. EGF-R expression was determined by measuring the specific Bmax of125I EGF to tumor plasma membrane preparations. Tumor with a B max ≥ 3 fmol/mg of protein were considered positive with regard to EGF-R expression. With a median follow-up of 34 months, the 3-year overall and disease-free survivals are respectively 92% and 88% for EGF-R ≤ 3, and 91% and 86% EGF-R 〉 3 fmol, showing no significant difference, even when comparing axillary lymph node status. We did not succeed in finding an EGF-R cut-off value which might be significant in univariate analysis. Multivariate analysis of our data indicates that pT (p = 0.001), pN (p = 0.04), and Scarff-Bloom grade (p = 0.04) are the only significant predictors of disease-free survival among the parameters investigated in this study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666480
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  • 47
    Electronic Resource
    Electronic Resource
    Second generation aromatase inhibitor — 4-hydroxyandrostenedione (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 81-87 
    Details
    ISSN: 1573-7217
    Keywords: 4-hydroxyandrostenedione ; aromatase ; aromatase inhibitor ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 4-hydroxyandrostenedione is a steroidal, suicide substrate inhibitor of aromatase, which has been widely tested in postmenopausal breast cancer patients. It is highly specific with the only notable endocrine changes other than oestrogen suppression being a dose-related suppression of sex-hormone binding globulin when the drug is given orally (a reflection of the drug's minor androgenic activity). Intramuscular administration of 250 mg every second week is the schedule of choice. This achieves peripheral aromatase inhibition of about 85% and oestradiol suppression of about 65%. The drug is usually used second-line, after tamoxifen, with an overall response rate in unselected patients of 26%. Side-effects are minimal and consist almost entirely of local reactions at the site of injection. 4-hydroxyandrostenedione is therefore a useful new treatment option as the first selective aromatase inhibitor to have wide clinical availability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682742
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  • 48
    Electronic Resource
    Electronic Resource
    Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 95-102 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; aromatase inhibitors ; CGS 20267 ; CGS 16949A ; hormone ablative therapy ; breast cancer treatment ; endocrine therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fadrozole Hydrochloride (CGS 16949A) and Letrozole (CGS 20267), are two of the newest non-steroidal, orally active aromatase inhibitors currently being evaluated as second line treatment of patients with hormone dependent forms of metastatic breast cancer. In a phase I clinical efficacy study, we examined the ability of these two imidazole derivatives to suppress the synthesis of estrogen in a cohort of postmenopausal patients with metastatic breast cancer. Both medications at relatively low doses were potent and rapid inhibitors of aromatase activity as evidenced by their ability to suppress the level of blood and urine estradiol and estrone as well as blood estrone sulfate in these patients. Letrozole appeared to be the more potent of the two, with over 95% suppression of both plasma and urinary estrogens observed within 2 weeks of therapy. Letrozole appeared to be more selective than Fadrozole in inhibiting aromatase activity in that no compromise in cortisol and aldosterone output was evident with Letrozole therapy at all of the doses tested, a compromise clearly seen with Fadrozole. The inhibition of aromatase activity by these imidazole derivatives as second line therapy for patients with hormone dependent breast cancer appears to be a favorable alternative form of hormone ablative therapy and holds considerable promise for the treatment of this malignancy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682744
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  • 49
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    Electronic Resource
    Hormonal carcinogenesis in breast cancer: cellular and molecular studies of malignant progression (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 237-248 
    Details
    ISSN: 1573-7217
    Keywords: malignant progression ; estrogen ; carcinogenesis ; hormone dependence ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have established and characterized a series of variant cell lines in which to identify the critical factors associated with E2-induced malignant progression, and the acquisition to tamoxifen resistance in human breast cancer. Sublines of the hormone-dependent MCF-7 cell line (MCF7/MIII and MCF7/LCC1) form stable, invasive, estrogen independent tumors in the mammary fat pads of ovariectomized athymic nude mice. These cells retain expression of both estrogen (ER) and progesterone receptors (PGR), but retain sensitivity to each of the major structural classes of antiestrogens. The tamoxifen-resistant MCF7/LCC2 cells retain sensitivity to the inhibitory effects of the steroidal antiestrogen ICI 182780. By comparing the parental hormone-dependent and variant hormone-independent cells, we have demonstrated an altered expression of some estrogen regulated genes (PGR, pS2, cathepsin D) in the hormone-independent variants. Other genes remain normally estrogen regulated (ER, laminin receptor, EGF-receptor). These data strongly implicate the altered regulation of a specific subset or network of estrogen regulated genes in the malignant progression of human breast cancer. Some of the primary response genes in this network may exhibit dose-response and induction kinetics similar to pS2, which is constitutively upregulated in the MCF7/MIII, MCF7/LCC1 and MCF7/LCC2 cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666157
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  • 50
    Electronic Resource
    Electronic Resource
    Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 249-261 
    Details
    ISSN: 1573-7217
    Keywords: stromal epithelial interactions ; insuline-like growth factors ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prominent ‘desmoplastic’ or stromal reaction seen in many invasive breast carcinomas lead to early speculation that stromal cells play a role in breast cancer pathogenesis [1]. Experimental evidence now supports this hypothesis and interactions between stromal cells and epithelial cells appear to be important for both normal mammary development and neoplasia. The identification of genes that are selectively expressed in the stroma of malignant breast lesions has recently provided new insights into the molecular basis of stromal-epithelial interactions. Stromally expressed genes include growth factors, proteases and extracellular matrix proteins, all biological activities with potential roles in malignant progression. Investigations discussed here concern the nature of the paracrine signals provided by malignant epithelial cells that activate changes in stromal gene expression, the effect that the stromally derived factors have on the behavior of malignant epithelial cells and the identification of novel factors and receptors in either stroma or epithelia that contribute to their mutual interactions. These questions will be addressed in the context of this laboratory's studies on insulin-like growth factors, as these molecules show marked differences in stromal expression between benign and malignant breast tissue and thus provide a useful paradigm for investigations into the paracrine environment of an evolving breast tumor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666158
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  • 51
    Electronic Resource
    Electronic Resource
    p53Val135 temperature sensitive mutant suppresses growth of human breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 167-177 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; oncogenes ; p53 transformation ; temperature sensitive mutant ; tumor suppressors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One common step in the malignant progression of a wide variety of human cancers seems to be inactivation of the p53 gene, via point mutation or deletion or both; or overexpression of mutated protein with dominant transforming activity. This study shows a suppressive effect of wild type p53 on the growth of human breast cancer cells. Introduction of wild type p53 versus mutant into five human breast cancer cell lines containing mutant p53 resulted in a marked reduction in colony formation. Two of these were transfected with human wt p53 expression vectors and the other three were infected with retroviruses packaging human wt p53, both showing similar reduction in the number of surviving colonies, suggesting a role for wt p53 in suppression of breast cancer cell growth. Direct evidence for growth suppression was obtained by introduction of the temperature sensitive p53Val135 into Hs578T human breast cancer cells containing a mutant p53. This murine mutant allele p53Val135 functions as an oncogene at 37° C and as a tumor suppressor at 32° C. The cell line generated was strongly growth inhibited at the restrictive temperature (31.5° C), at which temperature the suppressor form is expressed. This inhibition of proliferation was reversible upon a temperature upshift. Analysis of the cell cycle distribution shows these growth suppressed cells to be inhibited in the G1 phase of the cell cycle. Thus wt p53 may have an important role in breast cancer tumorigenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666061
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  • 52
    Electronic Resource
    Electronic Resource
    Immunosuppressive acidic protein serum levels in breast cancer patients in a reference to CA 15-3 levels (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 197-200 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CA 15-3 ; IAP ; immunosuppressive acidic protein ; tumor markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunosuppressive acidic protein (IAP) has been described as a tumor marker in a number of malignant diseases. To evaluate the clinical importance of IAP in breast cancer patients, IAP serum level was determined in 75 breast cancer patients, using single radial immunodiffusion. Serum samples were also tested for CA 15-3. Cut off value for IAP was determined according to IAP serum level in 50 patients with benign, non inflammatory, diseases, and was set as 725 microgram/ml. Mean IAP serum level (623 mcg/ml) and positivity rate (20%) in 24 breast cancer patients with active disease were similar to those in 51 breast cancer patients with no evidence of disease (590 mcg/ml and 18%). The mean CA 15-3 serum level and positivity rate were significantly higher in patients with active disease (200 units/ml, 67%), compared to patients with no evidence of disease (18.3 units/ml, 6%). In our experience IAP was not found to be an effective tumor marker in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666063
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  • 53
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    The incidence of hepatocellular carcinoma in US white women with breast cancer after the introduction of tamoxifen in 1977 (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 201-204 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; hepatocellular carcinoma ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been hypothesized that hepatocellular carcinoma might be a long-term adverse effect of tamoxifen therapy. Data from nine population-based cancer registries in the United States were used to investigate time trends in the incidence of hepatocellular carcinoma in white women previously diagnosed with invasive breast cancer during 1974–1987 and followed until 1989. Of particular interest were the rates after 1977, the year tamoxifen was licensed by the FDA. Compared to rates in all white women, no increased risk of hepatocellular carcinoma was found in women most likely to have received tamoxifen - those 50 years of age or more at diagnosis of breast cancer and diagnosed after 1977. These results suggest that tamoxifen does not cause a large increase in the incidence of hepatocellular carcinoma within the first decade after use. However, smaller and/or later increases in the risk for hepatocellular carcinoma are possible and warrant continued monitoring of women treated with tamoxifen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666064
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  • 54
    Electronic Resource
    Electronic Resource
    Phase II trial of 5-fluorouracil and folinic acid in the treatment of advanced breast cancer (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 205-209 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; folinic acid ; 5FU ; metastatic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Standard combination chemotherapy for metastatic breast cancer produces response rates between 30–60% with limited impact on survival. We undertook a phase II trial to determine the activity of 5 fluorouracil (5FU) and folinic acid (FA) in patients with measurable metastatic or recurrent breast cancer who had received no prior chemotherapy. Patients meeting the eligibility criteria received 5FU 370 mg/m2/day and FA 200 mg/m2/day for 5 days repeated every 28 days, toxicity allowing. Response defined by standard criteria was assessed every 8 weeks and toxicity according to WHO criteria was determined on every course. Thirty-three patients were entered on trial. Thirty-two patients were evaluable for response and 33 for toxicity. The dose limiting toxicity was stomatitis with 7/32, 19/32, and 5/32 patients experiencing grade 1, 2, and 3 toxicity. Grades 1 and 2 diarrhea occurred in 17/32 and 11/32 patients respectively. Myelosuppression was not significant. Two complete and 11 partial responses were observed. The overall response rate was 41% (95% CI, 24–58%). Responses were seen in soft tissue and visceral sites. Patients who had received adjuvant chemotherapy more than 6 months prior to receiving 5FU and FA responded also. Six of 29 patients receiving standard combination chemotherapy as second line treatment responded subsequently. We concluded: 1) 5FU and FA is an active combination in the treatment of breast cancer warranting further evaluation in combination with other drugs; 2) the dose-limiting toxicity of stomatitis is tolerable; 3) patients receiving 5FU and FA as first line therapy can respond to conventional combination chemotherapy as second line treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666065
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  • 55
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    Electronic Resource
    Monoclonal antibody BrE-3 participation in a multivariate prognostic model for infiltrating ductal carcinoma of the breast (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 243-261 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; monoclonal antibodies ; mucins ; multivariate analysis ; prognosis ; relapse ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibody (MoAb) BrE-3, an anti-human milk fat globule (HMFG) MoAb, is used here as a novel prognostic indicator for survival and relapse time in patients with infiltrating ductal carcinoma of the breast. A scoring system (4-Score method) was developed to this effect that measured, in a statistically reliable fashion, the level of expression of the epitope for MoAb BrE-3 in the cytoplasm and membranes of breast carcinoma cells in paraffin-embedded sections. In univariate analysis, data obtained by the 4-Score Method as well as data from traditional prognostic indicators (tumor size, axillary node status, and grade of differentiation) were found to be associated with patient survival and relapse. In multivariate analysis, using a Cox proportional hazards regression model, levels of expression of BrE-3 epitope plus tumor size and axillary node status were weighted and combined in an Individual Linear Composite Prognostic Score (ILCPS) that had a high level of association with survival and relapse time in this sample model of patients with infiltrating ductal carcinoma of the breast. This level of association was found to be higher than the level of association for any other combination of traditional or 4-Score method variables. The level of expression of BrE-3 significantly adds to the prognostic capacity of traditional prognostic markers for infiltrating ductal carcinoma of the breast.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665966
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  • 56
    Electronic Resource
    Electronic Resource
    Oral contraceptive use and the prognosis of breast cancer (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 283-292 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; oral contraceptives ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 471 breast cancer patients the influence of a positive history of oral contraceptive (OC) use on survival was investigated. 297 (63%) patients used OCs during any period of their life and 92 (20%) used them still at the time of diagnosis. Sixty months after diagnosis OC users had a significantly increased overall survival (p = 0.037). Survival rates amounted to 79.5% and 70.3% for OC users and non-users, respectively. The effect persisted after adjustment for other prognostic factors and was mainly attributed to women who had taken OCs four years or longer (p = 0.025). Comparing the survival after a 56 months median follow-up dependent on duration of OC use (never, 1–48 months, ≥ 49 months) in subgroups of prognostic factors, the most significant influence on survival was observed among long-term users with tumors more than 2 cm in diameter (p = 0.005), with axillary node-positive tumors (1–3 nodes, p = 0.055/≥ 4 nodes, p = 0.019), and with tumors of low estrogen receptor (p = 0.015) or progesterone receptor content (p = 0.04). The difference in survival between OC users and non-users cannot be explained by the distribution of prognostic factors investigated (histological type, histological grade, tumor size, lymph node involvement, hormonal receptor content). OC users had an even higher percentage of poorly differentiated tumors (p = 0.003). These results suggest an effect of OC use on tumor biology during the preclinical phase of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665969
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  • 57
    Electronic Resource
    Electronic Resource
    What do we know and what don't we know about tamoxifen in the human uterus (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 27-39 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogen ; breast cancer ; endometrial carcinoma ; endometrium ; tamoxifen ; uterus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since its introduction in the early seventies, the list of indications for the use of the antiestrogen tamoxifen has been continuously expanded. Tamoxifen is now used for the treatment of metastatic breast cancer and for long-term and often indefinite administration as an adjuvant therapy. Large clinical trials in three countries are now evaluating the efficacy of tamoxifen as a preventive agent. However, tamoxifen therapy has been associated with an increased incidence of endometrial carcinoma. Laboratory and clinical data available to date on this controversial issue can be summarized as follows: a) Tamoxifen can have an estrogenic effect on endometrium in the presence of low estrogen levels. b) Tamoxifen treatment is probably associated with an increased incidence of endometrial cancer; however, this association appears to be linked to higher tamoxifen doses (40mg/d). d) It is not known whether tamoxifen causes or allows the identification of occult endometrial carcinoma. e) At the present time there is evidence for a tumor promoting effect of tamoxifen on endometrial cancer at a dose of 20 mg per day. f) Replacement of tamoxifen by ‘pure’ antiestrogens or coadministration of progestins with tamoxifen do not appear to offer benefit unless clinical trials demonstrate a reduced incidence of endometrial problems. g) Patientsmust be evaluated for pre-exsisting endometrical carcinoma before starting tamoxifen therapy. f) Close followup of long-term tamoxifen patients with endometrial biopsies is recommended with individuals who experience symptoms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689674
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  • 58
    Electronic Resource
    Electronic Resource
    Molecular mechanisms of antiestrogen action in breast cancer (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 41-52 
    Details
    ISSN: 1573-7217
    Keywords: tamoxifen ; pure antiestrogens ; breast cancer ; prevention ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The success of antiestrogen therapy to treat all stages of breast cancer, and the evaluation of tamoxifen as a preventive for breast cancer in normal women, have focused attention on the molecular mechanisms of antiestrogen action and mechanisms of drug resistance. The overall goal of research is to enhance current therapies and to develop new approaches for breast cancer treatment and prevention. Recent studies show that tamoxifen and the new pure antiestrogens appear to have different mechanisms of action: tamoxifen and related compounds cause a change in the folding of the steroid binding domain that prevents gene activation whereas the pure antiestrogens cause a reduced interaction at response elements and cause a rapid loss of receptor complexes. Tamoxifen treatment produces changes in the cellular and circulating levels of growth factors that could influence both receptor negative or receptor positive tumor growth and the metastatic potential of a tumor. These events may explain the survival advantage observed with tamoxifen therapy. However, the current therapeutic challenge is to avoid drug resistance during long-term tamoxifen therapy. Numerous explanations for drug resistance to tamoxifen have been suggested, including elevated estrogen levels, increased tumor antiestrogen binding sites, receptor mutations, and impaired signal transduction. However, it is probable that multiple mechanisms evolve to facilitate tumor survival. Most importantly, current research is examining mechanisms responsible for the beneficial actions of tamoxifen on bones and lipids as well as the potentially deleterious effects of tamoxifen on liver and endometrial carcinogenesis and retinopathy. The urgent need to understand antiestrogenic drug mechanisms and toxicity is being facilitated by the application of the technology developed for basic molecular biology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689675
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  • 59
    Electronic Resource
    Electronic Resource
    Transcriptional regulation of multidrug resistance in breast cancer (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 263-271 
    Details
    ISSN: 1573-7217
    Keywords: MDR1 ; Sp1 ; p53 ; PKA ; 8-Cl-cAMP ; breast cancer ; multidrug resistance ; transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of cross-resistance to many natural product anticancer drugs, termed multidrug resistance (MDR), is one of the major reasons why cancer chemotherapy ultimately fails. This type of MDR is often associated with over-expression of theMDR1 gene product, P-glycoprotein (Pgp), a multifunctional drug transporter. The expression of MDR in breast tumors is related to their origination from a tissue that constitutively expresses Pgp as well as to the development of resistance during successive courses of chemotherapy. Therefore, understanding the mechanisms that regulate the transcriptional activation ofMDR1 may afford a means of reducing or eliminating MDR. We have found thatMDR1 expression can be modulated by type I cAMP-dependent protein kinase (PKA), opening up the possibility of modulating MDR by selectively down-regulating the activity of PKA-dependent transcription factors which upregulateMDR1 expression. High levels of type I PKA occurs in primary breast carcinomas and patients exhibiting this phenotype show decreased survival. The selective type I cAMP-dependent protein kinase (PKA) inhibitors, 8-Cl-cAMP and Rp8-Cl-cAMP[S] may be particularly useful for downregulating PKA-dependent MDR-associated transcription factors, and we have found these compounds to downregulate transient expression of a reporter gene under the control of severalMDR1 promoter elements. Thus, investigations of this nature should not only lead to a greater understanding of the mechanisms governing the expression of MDR, but also provide a focus for pharmacologic intervention by a new class of inhibitors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666159
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  • 60
    Electronic Resource
    Electronic Resource
    Antiestrogen resistance in ER positive breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 301-307 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; tamoxifen ; estrogen receptor ; antiestrogen resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acquisition of the antiestrogen resistance by breast cancer cellsin vivo may result from a variety of mechanisms. The main pathway appears to involve loss of estrogen receptor (ER) expression or selection for ER negative cells among heterogenous population of tumor cells. However, clinical data suggest that, in about 30% of the cases, antiestrogen resistance arises even in the presence of estrogen receptors. Postulated mechanisms leading to the latter phenotype include selection for variant receptor forms during treatment, development of novel metabolic pathways for the drug, loss of nuclear co-factors, or activation of signal transduction pathway that cross activate ER signals. We have used anin vitro experimental system utilizing LY-2 cell line, an ER positive and antiestrogen resistant MCF-7 cell variant, to study the mechanism of antiestrogen resistance in the presence of functional ER. Result from a complementation experiment suggests that LY-2 phenotype is a recessive trait. Cloning of the genetic defect in the LY-2 cells would provide further insight for the mechanism of antiestrogen resistance in ER positive breast cancer cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666162
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  • 61
    Electronic Resource
    Electronic Resource
    Positive immunostaining for platelet derived growth factor (PDGF) is an adverse prognostic factor in patients with advanced breast cancer (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 229-233 
    Details
    ISSN: 1573-7217
    Keywords: platelet derived growth factor ; PDGF ; breast cancer ; immunohistochemistry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies suggest a prognostic role for PDGF in patients with breast cancer, with patients with high plasma PDGF levels or positive response to therapy. We have examined a further 58 patients with advanced breast cancer for the presence of tissue PDGF immunostaining. Patients displaying positive tissue immunostaining for PDGF had a highly significant shorter survival (p = 0.002) than patients with no immunostaining. In addition PDGF positive patients treated with combination chemotherapy had a significantly lower response rate (p = 0.05) than PDGF negative patients. These results confirm our previous findings that PDGF may be an important indicator of shortened survival and treatment failure in patients with advanced breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665774
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  • 62
    Electronic Resource
    Electronic Resource
    Detection of prostate-specific antigen immunoreactivity in breast tumors (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 301-310 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; prognostic markers ; prostate specific antigen ; steroid hormone receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostate-specific antigen (PSA) is a glycoprotein produced by the epithelial cells of the prostate. PSA is currently used in clinical practice to facilitate diagnosis and monitoring of prostate carcinoma. The prostate is an organ that possesses androgen, estrogen, and progesterone receptors, and in this respect is similar to the breast. We postulated that breast tumors might also have the ability to produce PSA. We performed these studies on a collection of 525 tumor specimens collected for routine biochemical determination of estrogen and progesterone receptors. Using a highly sensitive immunofluorometric procedure, we measured the p53 tumor suppressor gene product and PSA. Twenty nine percent of the breast tumor extracts contained detectable levels of PSA immunoreactivity (〉 0.05 µg/L). The immunoreactive PSA content was associated with estrogen and/or progesterone receptor-positive tumors (P 〈 0.002). No association was found between PSA immunoreactivity and levels of the p53 tumor suppressor gene product (P = 0.37). High performance liquid chromatography and Western blot analysis revealed that the PSA immunoreactivity in the tumor had a molecular weight of 30 kDa, similar to that of seminal PSA. Immunoreactive PSA-positive tumors were associated with younger women (P = 0.012) and earlier disease stage (P = 0.064). We postulate that PSA immunoreactivity may be an additional marker of steroid hormone receptor-ligand action.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666007
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  • 63
    Electronic Resource
    Electronic Resource
    Natural killer cell activity, phagocytosis, and number of peripheral blood cells in breast cancer patients treated with tamoxifen (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 279-285 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; lymphocyte populations ; phagocytosis ; natural killer (NK) activity ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The number of leukocytes, proportion and absolute number of granulocytes, lymphocytes, CD4+ cells, CD8+ cells, CD16+ cells, B-lymphocytes, monocytes, natural killer cell (NK) activity, and granulocyte and monocyte phagocytic functions - ingestion and intracellular killing - were determined in a group of 27 patients with ductal invasive breast carcinoma, stage I-III, before and 7 months following postsurgical telecobalt radiotherapy, divided into two subgroups, one of them receiving tamoxifen (TMX group) and the other one not receiving any further therapy (control group). In control group, proportion of all lymphocytes and CD8+ cells as well as absolute number of all lymphocytes, CD4+, CD8+, CD16+ and B lymphocytes were decreased following TCT in comparison to their pre-TCT values, while in TMX group only absolute number of all lymphocytes remained decreased following TCT. Moreover, post-TCT proportions of all and CD8+ lymphocytes as well as absolute numbers of all and CD4+ and CD8+ lymphocytes in TMX patients were significantly increased in comparison to the same parameters in control post-TCT patients, although there was no difference between the two subgroups before TCT. At the other hand, granulocyte ingestion was decreased in post-TCT TMX patients compared to post-TCT values in control patients and NK cell activity showed a similar, although statistically not significant, tendency. It seems that TMX helps recovery of lymphocyte populations decreased by radiotherapy, probably by stimulation of cells carrying estrogen receptors, but its effects on phagocytic functions and probably NK cell activity seemed to be rather inhibitory than stimulatory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666482
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  • 64
    Electronic Resource
    Electronic Resource
    DNA ploidy and S-phase fraction in medullary carcinoma of the breast -a flow cytometric analysis using archival material (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 297-306 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA ploidy ; flow cytometry ; medullary carcinoma of the breast ; S-phase fraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a population of 110 primary breast cancers with medullary features, registered in the Danish Breast Cancer Cooperative Group (DBCG) from 1977-82, we have determined ploidy and S-phase fraction (SF) by flow cytometry (FCM) on paraffin embedded tumour tissue. The distribution of DNA ploidy is not different from the distribution described for breast cancers in general. No difference is found between the subgroups of medullary and non-medullary cancer when using a new simplified histopathological definition of medullary carcinoma of the breast, recently proposed by us. When using the definition proposed by Ridolfiet al. in 1977, we find significantly more tumours with aneuploidy and high SF in the groups of typical medullary carcinoma (TMC) and atypical medullary carcinoma (AMC) than in the small group of non-medullary carcinoma (NMC), which seems a paradox, as patients with NMC have the worst prognosis. However, the number of patients in the NMC group is very small, and the percentage of aneuploid tumours is very low. In 84 protocolled patients we found no statistically prognostic importance of ploidy or SF, either in the whole group assessed or when stratifying for the histopathological subgroups. However, a prognostic influence of SF can be traced for the non-medullary cancers, according to the new definition, but not for the medullary cancers of the breast. The result emphasizes the impression of MC as being biologically different from other histological types of breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666484
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  • 65
    Electronic Resource
    Electronic Resource
    The epidemiological profile of women with an interval cancer in the DOM screening programme (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 223-232 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; epidemiology ; interval cancer ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risk factors for breast cancer were compared in 107 women with interval breast cancer (cancers occurring within 2 years after a negative screen) and 258 women with breast cancer detected at 1st screening. All women (aged 40–67) were screened in the DOM project (the Utrecht programme for the early detection of breast cancer). Women with an interval cancer reported more often a history of benign breast disease (OR 4.66, 95% C.I. 2.08-10.41) and an artificial menopause (OR 4.07; 95% C.I. 1.74-9.55) than women with a screen detected cancer. Women with an interval cancer were taller than women with a screen detected cancer; this was seen most clearly in women with an artificial menopause (X 2 for trend = 5.88; p = 0.02) and to a lesser extent in premenopausal women (X 2 for trend = 1.70; p = 0.19). Premenopausal women with an interval cancer were heavier than women with a screen detected cancer (X 2 for trend = 4.66; p = 0.03); whereas natural postmenopausal women with an interval cancer were leaner than women with a screen detected cancer (X 2 for trend = 1.57; p = 0.21). All analyses were done while correcting for age and selected other risk factors for breast cancer. These results suggest that the epidemiological profile of pre- and post-menopausal women with an interval cancer differs from that of women with a screen detected cancer, which might imply a different natural history of these two types of breast tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665964
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  • 66
    Electronic Resource
    Electronic Resource
    Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer (1994)
    Springer
    Breast cancer research and treatment 30 (1994), S. 263-274 
    Details
    ISSN: 1573-7217
    Keywords: aspiration ; breast cancer ; biomarkers ; prediction ; risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p 〈 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p 〈 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665967
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  • 67
    Electronic Resource
    Electronic Resource
    Constitutive overexpression of the 27,000 dalton heat shock protein in late passage human breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 177-186 
    Details
    ISSN: 1573-7217
    Keywords: hsp27 ; gene regulation ; breast cancer ; heat shock transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We present evidence that the mechanisms controlling induction of heat shock transcription factors (HSFs) and mRNA expression of the 27,000 molecular weight heat shock protein, hsp27, are diverse in human breast cancer cells. Heat shock accumulation of hsp27 RNA is associated with the activation of HSF in MDA-MB-231 cells. We have later passage MCF-7 breast cancer cell lines with elevated, constitutive expression of hsp27 mRNA, perhaps due to hsp 27 gene amplification. Estradiol and heat shock treatment no longer affect the level of hsp27 mRNA in these cells. Heat induction of HSF is inhibited in cells overexpressing hsp27, although metal ions and amino acid analogs are still capable of activating HSF. These cells will provide a useful system for characterizing alternative pathways in HSF inhibition and activation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665768
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  • 68
    Electronic Resource
    Electronic Resource
    The relationship of urinary and plasma androgens to steroid receptors and menopausal status in breast cancer patients and their influence on survial (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 203-212 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; androgens ; menopausal status ; oestrogen receptor ; progesterone receptor ; age ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7α-hydroxy DHA (7αDHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665771
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  • 69
    Electronic Resource
    Electronic Resource
    Are cellular adhesion molecules involved in the metastasis of breast cancer? (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 239-260 
    Details
    ISSN: 1573-7217
    Keywords: adhesion molecule ; breast cancer ; malignant disease ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666002
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  • 70
    Electronic Resource
    Electronic Resource
    Fine-needle aspiration technique for the concurrent immunocytochemical evaluation of multiple biologic parameters in primary breast carcinoma (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 221-228 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen and progesterone receptors ; Ki67 antigen ; p53 protein ; fine-needle aspiration cytology ; immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fine-needle aspiration cytology has been already established as a reliable method for the diagnosis of breast cancer. Its application has been recently extended to immunocytochemical analysis of biological parameters. In the current study estrogen and progesterone receptors, Ki67 growth fraction, and p53 protein expression were immunocytochemically evaluated on the cellular material sampled by the same fine-needle aspirate used for the conventional cytologic diagnosis of malignancy. Fine-needle aspiration specimens from 100 patients with primary breast carcinoma were submitted to the immunocytochemical analysis. Twenty-eight percent were in premenopause; 23% had tumors with a diameter less than 2 cm, 59% from 2 to 5 cm, and 18% more than 5 cm; 60% had axillary nodal status negative, 34% positive, and 6% unknown. The concomitant immunocytochemical evaluation of all parameters was possible in 70% of the patients. A significant association was found between p53 overexpression and Ki67 values (p = 0.004), and between Ki67 values and progesterone receptor status (p = 0.003). No correlation was found between any parameter and clinical tumor size. Estrogen (p = 0.02) and progesterone (p = 0.04) receptor negativity and high Ki67 growth fraction (p = 0.005) were significantly associated with the clinical evidence of axillary node involvement. This study suggests that fine-needle aspiration cytology represents an effective practice for a simultaneous evaluation of multiple biologic indicators and could be useful as a preoperative procedure in patients who are candidates for neoadjuvant chemotherapy and/or endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665773
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  • 71
    Electronic Resource
    Electronic Resource
    The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG) (1994)
    Springer
    Breast cancer research and treatment 32 (1994), S. 281-290 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; histological grade ; lymph-node staging ; prognostic factors ; multivariate prognostic index ; survival ; tumour size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In primary, operable breast cancer, the Nottingham Prognostic Index (NPI) based on tumour size, lymphnode stage and histological grade can identify three prognostic groups (PGs) with 10-year survival rates of 83%, 52%, and 13%. With the aim of defining a subset of patients having so good prognosis that adjuvant therapy can be withhold, the NPI was applied to a Danish population-based study group comprising 9,149 patients. As opposed to the British study, we used conventional axillary lymph-node staging. Histological grading was in both studies done by means of a similar slight modification of the Bloom and Richardson procedure, but in the Danish study only ductal carcinomas were graded. The 10-year crude survival was 68.1% for 4,791 patients with tumour size ≤ 2 cm and 70.0% for 2,900 patients with grade I tumours. For 4,761 node-negative patients, the 10-year survival was also 70.0%, the expected survival being 89.3%. The relative mortality (observed:expected) was even at 10 years 2.1 demonstrating that more than 10 years observation time is necessary to estimate cumulated mortality. By application of the NPI, the Danish good PG comprising 27.3% of the patients had a 10-year survival of 79.0%. Thus, the index defined a subset with better survival than could be defined individually by each of its three components, but it did not succeed in defining a subset with survival similar to the expected; additional prognostic factors are therefore needed. The somewhat poorer survival of the Danish good PG may be ascribed to the British inclusion of non-ductal carcinomas, to interobserver variation present only in the Danish study, and to poorer expected survival of the Danish patients. The 10-year survival of the Danish moderate PG and poor PG was 56% and 25%, respectively. These improved survival rates are attributed to the administration of adjuvant therapies. There were virtually no node-positive patients in the good PG and no node-negative patients in the poor PG. Patients should therefore still be stratified initially by lymph-node status, but tumour size and histological grade are significant prognostic factors primarily within the node-negative group, and they should be included in future prognostication procedures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666005
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  • 72
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    Electronic Resource
    Droloxifene, a new antiestrogen: Its role in metastatic breast cancer (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 83-94 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; breast cancer ; droloxifene ; clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Droloxifene, a new antiestrogen, has theoretical advantages over tamoxifen based on preclinical data. These include higher affinity to the estrogen receptor, higher antiestrogenic to estrogenic ratio, and more effective inhibition of cell growth and division in ER positive cell lines, as well as less toxicity, including reduced carcinogenicity in animal models. Droloxifene also exhibits more rapid pharmacokinetics, reaching peak concentrations and being eliminated much more rapidly than tamoxifen. A phase II study compared droloxifene in dosages of 20, 40, and 100 mg daily in postmenopausal women with metastatic, or inoperable recurrent, or primary locoregional breast cancer who had not received prior hormonal therapy. Of 369 patients randomized, 292 were eligible and 268 evaluable for response. Response rates (CR + PR) were 30% in the 20 mg group, 47% in the 40 mg group, and 44% in the 100 mg group (40 mg vs 20 mg, p = 0.02; 100 mg vs 20 mg, p = 0.04; pooled 40 + 100 mg vs 20 mg, p = 0.01). Median response duration also favoured the higher dosages (20 mg group = 12 months; 40 mg group = 15 months; 100 mg group = 18 months). When adjusted for prognostic factors, time to progression was significantly better for the 100 mg (p = 0.01) and the 40 mg (p = 0.02) group compared to the 20 mg group. Droloxifene increased SHBG and suppressed FSH at all dosages and suppressed LH at the 40 and 100 mg dosages. These hormonal effects increased with increasing dosage. Shortterm toxicity was generally mild, and similar to that seen with other antiestrogens. Droloxifene appears active and tolerable. It may have a particular role in situations in which rapid pharmacokinetics, or an increased antiestrogenic to estrogenic ratio, are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689679
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    Antiestrogen regulation of cell cycle progression and cyclin D1 gene expression in MCF-7 human breast cancer cells (1994)
    Springer
    Breast cancer research and treatment 31 (1994), S. 95-105 
    Details
    ISSN: 1573-7217
    Keywords: antiestrogens ; cell proliferation ; cell cycle ; cyclins ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The molecular mechanisms by which antiestrogens inhibit breast cancer cell proliferation are not well understood. Using cultured breast cancer cell lines, we studied the effects of antiestrogens on proliferation and cell cycle progression and used this information to select candidate cell cycle regulatory genes that are potential targets for antiestrogens. Under estrogen- and serum-free conditions antiestrogens inhibited proliferation of MCF-7 cells stimulated with insulin. Cells were blocked at a point in G1 phase. These effects are comparable with those in serum- and estrogen-containing medium and were also seen to a lesser degree in nude mice bearing MCF-7 tumors. Similar observations with other peptide mitogens suggest that the process inhibited by antiestrogens is common to estrogen and growth factor activated pathways. Other studies have identified G1 cyclins as potential targets for growth factor and steroid hormone/steroid antagonist regulation of breast epithelial cell proliferation. In MCF-7 cells growing in the presence of fetal calf serum, cyclin D1 mRNA was rapidly down-regulated by steroidal and nonsteroidal antiestrogens by an apparently estrogen receptor mediated mechanism. Cyclin D1 gene expression was maximally inhibited before effects on entry into S phase and inhibition was therefore not merely a consequence of changes in cell cycle progression. Together with data on the effects of antiestrogens in serum-free conditions [1], these results suggest down-regulation of cyclin D1 by antiestrogens may be a general phenomenon in estrogen receptor-positive breast cancer cells, independent of culture conditions and class of antiestrogen. These observations are compatible with the hypothesis that reductions in cyclin D1 levels may mediate in part the action of antiestrogens in blocking entry of cells into S phase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689680
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    Clonal dominance detected in metastases but not primary tumors of retrovirally marked human breast carcinoma injected into nude mice (1994)
    Springer
    Clinical & experimental metastasis 12 (1994), S. 3-12 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; clonal dominance ; retroviral gene transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Human breast cancer cell lines which grow in athymic (nude) mice provide a model of tumor cell growth and metastasis. Marking transplanted tumor cell populations with retroviral vectors provides a means of studying the dynamics of tumor cell growthin vivo. We evaluated three human breast cancer cell lines, MDA-MB-435, MDA-MB-231 and MCF-7, and found the cells were highly susceptible to retroviral gene transfer after a single 2-h exposure (90.9%, 62.7% and 72.3%, respectively). MDA-MB-435 cells (5×105) marked with a retroviral vector containing theβ-galactosidase gene (approximately 104 uniquely marked clones) were injected into the mammary fat pad of athymic mice to study clonal dominance. Primary tumors resected 10 weeks after injection expressedβ-galactosidase, demonstrating persistent vector expressionin vivo. Southern blot analysis did not reveal clonal dominance in the primary tumors of the five mice studied. In contrast, pulmonary metastases in each animal were monoclonal or biclonal. These results demonstrate clonal dominance in pulmonary metastases but not primary tumors of retrovirally marked MDA-MB-435 cells. Our findings suggest that this model may also be used to introduce retroviral vectors expressing oncogenes, and anti-sense oncogenes, to determine their effect on tumor cell proliferation and metastasisin vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01784328
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    A case-control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects (1994)
    Springer
    Cancer causes & control 5 (1994), S. 157-165 
    Details
    ISSN: 1573-7225
    Keywords: Atomic bomb survivors ; breast cancer ; Japan ; reproductive history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women with breast cancer (cases=196) and without the disease (controls=566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]2) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01830262
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    Regional and age variations in growing tendon (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 221 (1994), S. 309-320 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Gastrocnemius tendons of 10 White Leghorn chickens at 6, 8, and 12 weeks of age were divided into proximal, middle, and distal portions to assess regional variability in composition and growth. Body weight increases ∼ 150% during the period examined, whereas the lateral gastrocnemius muscle and tendon increase ∼ 193% and 227%, respectively. No significant changes in cellularity (DNA concentration) or hydroxypyridinium (OHP) crosslinks occur with increasing age. Hydroxyproline (HYP) concentration increases by 12 weeks of age, as hexuronate, glucosamine, and galactosamine decrease. Composition shows some regional variation: the distal region of the tendon has a lower HYP concentration, and increased GAGs and OHP crosslinks compared to either the proximal or middle regions, which do not differ from each other. The mean collagen fibril diameter increases with age, but the oldest tendons also contain more small diameter fibrils (〈40 nm). There is a unimodal fibril distribution at all three ages, although this has broadened by 12 weeks. The data from this study suggest that rapid tendon growth occurs throughout the time period examined and that changes characteristic of mature tendon, such as increased OHP crosslink concentration, have not yet developed in hatchlings because of the large amount of new tissue being produced. Whereas all three regions of the tendon are similar in size, composition of the distal region differs from that of the proximal and middle regions, suggesting that this portion of the tendon should be avoided when sampling a tendon. © 1994 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052210306
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    Microscopic anatomy of pycnogonida: I. Cuticle, epidermis, and muscle (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 33-48 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The integument of Pycnogonida (Arthropoda) consists of an epicuticle decorated with tubercles and a filamentous coat, an exocuticle with a small number of ill-defined layers, and an endocuticle whose numerous layers are composed of conspicuously cross-banded fibrils. This cuticular periodicity, attributable to cross-linked chitin, has been observed previously in uncalcified and untanned cuticle of many lower crustaceans, especially branchiopods and copepods, and in scattered examples of thin respiratory or excretory cuticles of other arthropods. It is uniformly present in all representatives of all nine pycnogonid families examined to date. Stomodeal, proctodeal, and arthrodial cuticles are devoid of the endocuticular periodicity. The cuticle is decorated with sensory filaments and setae, but is more noteworthy for a dense coverage by glands, up to 1,400/mm2. Myocuticular junctions have desmosomal fine structure previously found only in chelicerates. Muscle fine structure is that of slow fibers with long sarcomeres and a high actin to myosin filament ratio, except for cardiac muscle, which has short sarcomeres. Among the arthropods, only merostomates resemble the pycnogonids in the lack of fast somatic muscle fibers. Pycnogonids display a hybrid array of fine structural features that variously serve to relate them to some arthropod subphyla and distance them from others. © 1994 Wiley-Liss, Inc.
    Additional Material: 15 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220105
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    Erratum (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 111-111 
    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.1052220111
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    Development and growth of compound tooth plates in Callorhinchus milii (chondrichthyes, holocephali) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 73-89 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The chimaeroid holocephalian fishes are distinguished among extant chondrichthyans by the possession of three pairs of tooth plates, evergrowing and partially hypermineralized, that are not shed and replaced like the teeth of living elasmobranchs. Although derivation of the chimaeroid tooth plate from the fusion of members of a plesiomorphic chondrichthyan tooth family has been proposed, evidence for this hypothesis has been lacking. A new analysis of the development and structure of the tooth plates in Callorhinchus milii (Holocephali, Chimaeriformes) reveals the compound nature of the tooth plates in a chimaeroid fish. Each tooth plate consists of an oral and aboral territory that form independently in the embryo and maintain separate growth surfaces through life. The descending lamina on the aboral surface of the tooth plate demarcates the growth surface of the aboral territory. Comparison with the tooth plates of Chimaera monstrosa indicates that compound tooth plates may be a feature of all chimaeroids in which a descending lamina is present. The tooth plates in these fishes represent the fusion of two members of a reduced tooth family. The condition of the tooth plates in C. milii is plesiomorphic for chimaeroids and is of evolutionary significance in that it provides further evidence to support a lyodont dentition in chimaeroid fishes similar to that found in other chondrichthyans. © 1994 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220108
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    Morphological and functional body reconstruction in a teleost of the genus Oreochromis (Cichlidae) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 1-6 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The process of morphological and functional regeneration was followed on a tilapid fish, a cross of Oreochromis aureus × Oreochromis niloticus, by observations on movements and the use of X-rays. A four-year-old adult fish that lost its tail as post larva, including ten vertebrae, was able to reconstruct a novel and shorter central skeleton, including a specially modified urostyle. The enlarged and strengthened pterygiophores and their junctions with the dorsal and anal spine formed a fast-holding base for the fins, the posterior part of which largely performed the functions of the missing caudal fin. Although the fish was much shorter than usual, this male behaved and functioned normally. © 1994 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190102
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    Ultrastructure of the paraphysis in Bufo bufo larvae (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 7-13 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A study of the ultrastructure and function of the paraphysis in Bufo bufo larvae was carried out. The structure is a tubular-ramified gland made up of numerous tubules with monolayered epithelial walls surrounded by connective tissue and sinusoids. The epithelial cells secrete glycoprotein to contribute to production of the cephalorachidian fluid. The role of the paraphysis in the transport of fluids and electrolytes from the blood to the cephalorachidian fluid in regulation of ionic and osmotic homeostasis is discussed. © 1994 Wiley-Liss, Inc.
    Additional Material: 14 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190103
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    Characteristics of the flagellar axoneme in Neuroptera, Coleoptera, and Strepsiptera (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 15-20 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Spermatozoa from representatives of the five insect orders in superorder Neuropteroidea were examined by electron microscopy following a new fixation method that includes tannic acid in the primary fixative but has uranyl acetate rather than osmium tetroxide as the secondary fixative. The sperm axoneme was found to be similar in the four orders Megaloptera, Raphidioptera, Neuroptera, and Coleoptera, and is characterized above all by its so-called intertubular material being divided into two portions, one located outside, but in contact with the doublet, and the other projecting from the accessory tubule and having a beak-like shape. These features have not been seen in insects from other orders and may be a synapomorphy for these neuropteroid orders. The accessory tubules in these four orders have 16 protofilaments. The shape of the accessory bodies adjacent to the mitochondrial derivatives is nearly the same in insects from the more primitive neuropteroid orders and in Coleoptera. The sperm tail of the examined strepsipteran deviates in several respects from that of other neuropteroids: the particle row in the wall of accessory tubules is incomplete, an intertubular material is missing, and the mitochondria contain no crystal. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190104
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    Spiral cleavage and cell position contribute to the specification of the dorsoventral axis in the embryo of the archaeogastropod Haliotis tuberculata (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 21-33 
    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 embryo of Haliotis tuberculata spiral cleavage induces size differences between the quadrants in the 4-cell embryo. These size differences, together with the formation of compact cell configurations, induce asymmetrical positions of equivalent cells in the 8- and 16-cell embryo. The asymmetries in size and position influence the final specification of the dorsoventral asymmetry in the 32-cell embryo, as well as formation of the mesentoblast. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190105
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    Eversible abdominal vesicles and some observations of the male reproductive system of the spoon wing lacewing Palmipenna (Neuroptera: Nemopteridae) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 47-58 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The anatomy and histology of the abdominal eversible vesicles and the male reproductive tract of the spoonwing lacewing Palmipenna (Neuroptera: Nemopteridae) have been examined. The eversible vesicles open as a pair of large bulbous sacs between tergites five and six, each folding into halves during retraction. They consist of highly pleated cuticle, beneath which are typical gland cells, each having a circular or oval end apparatus surrounded by closely packed microvilli. These communicate to the surface via cuticularized channels. In spite of considerable behavioral observations, male Palmipenna were never noted with everted vesicles. Even during mating trials, where females were presented to males in the field, the vesicles were never everted during the attempted copulation that ensued. Our observations indicate that mate attraction is mediated by the release of a female pheromone. The function of the eversible vesicles and their associated gland cells remains unknown, and their structure appears to be unique to the Nemopteridae. The reproductive tract is similar to that of other Neuroptera, consisting of a pair of five-lobed testes, a medium-to-large pair of seminal vesicles, and three pairs of accessory glands. The major accessory glands are surrounded by circular and longitudinal muscle, and are lined by an epithelium, the cells of which presumably secrete the amorphous rods of material always present in this pair of glands. The sperm in the seminal vesicles are elongate, with a pointed head and a 9 + 9 + 2 configuration in the flagellum. A single spermatophore, similar in shape to that described for other Neuroptera, was found occluding the bursa copulatrix of a teneral female. © 1994 Wiley-Liss, Inc.
    Additional Material: 24 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190107
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    In vivo fluorescence imaging of the functional organization of trophotaenial placental cells of goodeid fishes (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 35-46 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Embryos of viviparous goodeid fishes undergo a 10 to 150 × increase in dry weight during gestation. Maternal nutrients are transferred across a trophotaenial placenta comprised of the ovarian lumenal epithelium and the trophotaeniae of the embryo. Trophotaeniae are externalized projections of the embryonic hindgut. Epithelial cells of the ribbon trophotaenia (Ameca splendens) resemble intestinal absorptive cells of suckling mammals and endocytose macromolecules. They possess an apical brush border, endocytotic complex, endosomal-lysosomal system, and apical and basal clusters of mitochondria. Cells of the rosette trophotaenia (Goodea atripinnis) lack an endocytotic apparatus, have small lysosomes, two mitochondrial clusters, and transport small molecules. Organelle-specific fluorescent probes were employed to characterize the functional organization of the two types of trophotaenial cells. In A. splendens, Lucifer Yellow, a membrane-impermeable tracer of vesicular transport, first appears in peripheral vesicles (15-45 sec), then passes into elongated tubular endosomes (1-3 min) and later appears in large central vacuoles (10-15 min). These vacuoles accumulate Acridine Orange, a classical probe for lysosomes, and have been shown to contain lysosomal enzymes. Endosomelysosome fusion was observed. In both A. splendens and G. atripinnis, Rhodamine 123 fluorescence was localized in two clusters of fine spots that corresponded to mitochondria. 4′,6-diaminido-2-phenyl-indole (DAPI) staining of nuclei established the positional relationships of cell organelles with respect to the nuclei. 3,3′-dihexyloxacarbo-cyanine iodide (DiOC6) revealed the perinuclear distribution of the endoplasmic reticulum. In order to compare in vivo fluorescence of Lucifer Yellow with previous ultrastructural observations, we employed fluorescence photoconversion and electron microscopy. © 1994 Wiley-Liss, Inc.
    Additional Material: 15 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052190106
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    Ontogenesis and ultrastructure of seminal vesicles of the catfish, Clarias gariepinus (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994), S. 59-71 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The ontogenesis and structural characteristics of the seminal vesicles in Clarias gariepinus (sharptooth catfish) were studied by light and electron microscopy and are described in detail. The seminal vesicles, beginning as simple protrusions from the vas efferentia, becomes more complex with age. Their distal ends become fingerlike and the bases form palm-like extensions. Juvenile male organs do not reveal any signs of seminal vesicles although spermatogenic tissue is already well delineated. The developing gonads contain clusters of large cells, close to the sperm duct and cysts of the testis, from which seminal vesicles are formed. Secretory epithelium lines the tubules of the seminal vesicles and becomes columnar as the tissue matures. Electron micro-graphs of these epithelial cells reveal two types of cells: opaque cells and cells with very vacuolized cytoplasm. Dense pinocytotic vesicles are present between the membranes of neighbouring seminal tubules and apical cell membranes facing the lumen. Maturation and onset of secretion by the secretory cells is accompanied by morphological changes. Protruding cylindrical cells become shortened, modified to cuboidal, rounded cells that send tubular extensions into the lumen. In the final stage of differentiation, only connective tissue membranes supporting the tubule walls remain intact. At the points of contact between the testis, seminal vesicles, and sperm duct, the epithelia of these organs often become confluent. The distal parts of the seminal vesicles, rarely contain sperm; during spawning sperm accumulated in the proximal tubules of the vesicles. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 219 (1994) 
    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.1052190201
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    External morphology and abundance of antennal sensilla in australian gryllacrididae (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 11-18 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The long (49-93 mm) antennae of two species of Australian gryllacridids have high total numbers of sensilla consisting of five sensillar types. Ametrus sp. 7 has 22,300 (♀) and 26,250 (♂) sensilla; although the antennae of males are 33% longer than those of females, their sensillar density was 11% less. Bothriogryllacris pinguipes has 26,700 (♂) and 31,900 (♀) sensilla; antennae of females are 55% longer than those of males but sensillar density is 23% less. Aporous sensilla chaetica form 94.5 to 99.5% of all sensilla; they are presumably mechanoreceptors. Uniporous trichoid contact chemoreceptors range from 75-900 in number. Olfactory, multiporous, basiconic sensilla range from 22-440 and olfactory, coeloconic sensilla from 16-235. Two to five multiporous lenticular organs occur on all but female A. sp. 7. Differences in sensillar abundance between males and females are discussed as well as are the relationships between sensillar diversity on gryllacridid mouthparts and antennae. © 1994 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220103
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    Immunofluorescent studies on titin and myosin in developing hearts of normal and cardiac mutant axolotls (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 19-32 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Homozygous recessive cardiac mutant gene c in the axolotl, Ambystoma mexicanum, results in a failure of the embryonic heart to initiate beating. Previous studies show that mutant axolotl hearts fail to form sarcomeric myofibrils even though hearts from their normal siblings exhibit organized myofibrils beginning at stage 34-35. In the present study, the proteins titin and myosin are studied using normal (+/+) axolotl embryonic hearts at stages 26-35. Additionally, titin is examined in normal (+/c) and cardiac mutant (c/c) embryonic axolotl hearts using immunofluorescent microscopy at stages 35-42. At tailbud stage-26, the ventromedially migrating sheets of precardiac mesoderm appear as two-cell-layers. Myosin shows periodic staining at the cell peripheries of the presumptive heart cells at this stage, whereas titin is not yet detectable by immunofluorescent microscopy. At preheartbeat stages 32-33, a myocardial tube begins to form around the endocardial tube. In some areas, periodic myosin staining is found to be separated from the titin staining; other areas in the heart at this stage show a co-localization of the two proteins. Both titin and myosin begin to incorporate into myofibrils at stage 35, when normal hearts initiate beating. Additionally, areas with amorphous staining for both proteins are observed at this stage. These observations indicate that titin and myosin accumulate independently at very early premyofibril stages; the two proteins then appear to associate closely just before assembly into myofibrils. Staining for titin in freshly frozen and paraffin-embedded tissues of normal embryonic hearts at stages 35, 39, and 41 reveals an increased organization of the protein into sarcomeres as development progresses. The mutant siblings, however, first show titin staining only limited to the peripheries of yolk platelets. Although substantial quantities of titin accumulate in mutant hearts at later stages of development (39 and 41), it does not become organized into myofibrils as in normal cells at these stages. © 1994 Wiley-Liss, Inc.
    Additional Material: 21 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052220104
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    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994) 
    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.1052220201
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  • 91
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    Quantitative design of the skeleton in bird hatchlings: Does tissue compartmentalization limit posthatching growth rates? (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 113-131 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Based on a detailed description of hatchling skeletons of the precocial buttonquail (Turnix suscitator) and the altricial budgerigar (Melopsittacus undulatus), this report presents the hypothesis that the rate of avian posthatching growth is limited by the quantitative design (i.e., relative volumes of cartilage, bone, and marrow) of the hatchling skeletons. A Jarge portion of bone in the skeletal elements and fast growth are hypothesized to be mutually exclusive. This hypothesis is tested by morphometric techniques and by statistical comparison of morphometric and growth data. All predictions are met by the data, and the design of hatchling skeletons is described as determined by a tradeoff between tissue composition of skeletal elements and maximum rates of posthatching growth. The precocial design shows large bony areas that supposedly resist mechanical stress of locomotion; however, the relatively small cartilaginous areas exclude high growth rates. The altricial design shows the reverse relationship with small bony areas and a lack of locomotion on the one side but large cartilaginous areas and fast posthatching growth on the other side. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220202
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  • 92
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    Kinematic analysis of jaw protrusion in orectolobiform sharks: A new mechanism for jaw protrusion in elasmobranchs (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 175-190 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Jaw protrusion is an important component of prey capture in fishes, although the mechanics of protrusion have thus far been studied largely in teleosts. Elasmobranchs are also able to protrude their jaws (Tricas and McCosker [1984] Proc. Cal. Acad. Sci. 43: 221-238; Tricas [1985] Mem. S. Calif. Acad. Sci. 8:81-91.; Frazzetta and Prange [1987] Copeia 4:979-993). Several related features of the feeding apparatus contribute to jaw protrusion in sharks. Labial cartilages form an extendible series attached dorsally to the anterolateral face of the palatoquadrate and ventrally to the anteroventral surface of Meckel's cartilage. The labial cartilage chain swings anterolaterally as the lower jaw is depressed, thrusting the labial margins forward to form a circular oral opening and displacing the jaw apparatus towards the food; this pattern is analogous to halecomorph and primitive actinopterygian fishes in which the maxilla swings forward (Lauder [1979] J. Zool. Lond. 187:543-578). The palatoquadrate and Meckel's cartilage also project anteriorly and represent the major contribution to protrusion. These movements occur simultaneously with enlargement of the oral cavity to generate suction. The wobbegong sharks (Orectolobidae) are specialized for jaw protrusion. The spotted wobbegong protrudes its jaw by 33% of its chondrocranial length using two different mechanical systems. In the first mechanism of jaw protrusion, the intermandibularis and interhyoideus muscles medially compress the lower jaw and hyomandibulae. Compression of the lower jaw results in a more acute symphyseal angle so that the anteroposterior alignment of the lower jaw increases due to the rotation of each lower jaw towards a saggital orientation. Distal compression of the hyomandibulae at their attachments to the jaws swings the jaws forward. The second mechanism involves rotation of the ceratohyal around a posterior process of the lower jaw, pushing the hyomandibulae anteroventrally, thereby pushing the jaw articulation ventrally and anteriorly to protrude the jaws. © 1994 Wiley-Liss, Inc.
    Additional Material: 13 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220205
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  • 93
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    Localization and distribution of gap junctions in normal and cardiomyopathic hamster heart (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 203-213 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Gap junctions in mammalian heart function to provide low-resistance channels between adjacent cells for passage of ions and small molecules. It is clear that the almost unrestricted passage of ions between cells, ionic coupling, is required for coordinate and synchronous contraction. This knowledge of gap junction function has made it important to study their properties in normal and abnormal tissues. In the present study, we analyzed gap junction distribution in normal and cardiomyopathic heart tissue utilizing immunofluorescent and electron microscopy techniques. Frozen, unfixed sections of age-matched normal and cardiomyopathic cardiac tissues were immunofiuorescently stained using an antibody directed against a specific peptide sequence of the connexin-43 gap junction protein. These studies revealed a characteristic punctate staining pattern for the intercalated discs in normal tissues. Some of the intercalated discs in cardiomyopathic hearts appeared to stain normally; however, others stained diffusely. The pixel intensity distribution of the confocal images demonstrated a marked difference of up to 90% increase in the number of pixels in cardiomyopathic myocardium (CM), yet the pixel intensity of gap junctions had a decrease of approximately 60%. This suggests the possibility that connexin-43 is present in CM cells in significant quantity; however, it does not become localized on the membranes as in normal cells. Electron-microscopic findings corroborate these observations on CM cells by showing an irregular distribution of intercalated discs relatively smaller in size with abnormal orientation and distribution. © 1994 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220207
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  • 94
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    Masthead (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994) 
    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.1052220301
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  • 95
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    Phylogenetic implications of structure of adult ovary and oogenesis in the penicillate diplopod, Eudigraphis nigricians (miyosi) (diplopoda: Myriapoda) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 223-230 
    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 some significant structures of the adult ovary in a Japanese penicillate diplopod, Eudigraphis nigricans, with respect to phylogenetic implications. The ovary is a long, saclike organ lying between the alimentary canal and the ventral nerve cord from the fourth through the ninth body segment. The ovarian wall consists of a thin ovarian epithelium and a sparse muscle covering. There are two types of oogenetic sites: a single, mound-shaped germarium sitting on the center of the ventral ovarian epithelium, and ∼ 10 pairs of patchlike vitellarial areas metamerically arranged anterior and posterior to the germarium. The germarium consists of oogonia, early previtellogenic oocytes, and some somatic interstitial cells. In contrast, the vitellarial areas are composed of more advanced oocytes, follicle cells surrounding the oocytes, and some interstitial cells, but no oogonia. A few larger previtellogenic oocytes rise up from each vitellarial area into the ovarian lumen. Each of these oocytes is still connected with its own vitellarial area by a partial extension of its follicle. Vitellogenesis takes place in these oocytes rising in the ovarian lumen. The ripe primary oocytes leave their follicles to be transported forward into the oviducts. Some phylogenetic implications of the basic characteristics in ovarian structure and oogenesis of E. nigricans are discussed. © 1994 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220302
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    Morphology of shells from viable and nonviable eggs of the chinese alligator (Alligator sinensis) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 103-110 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The morphology of eggshells from hatched eggs of captive Chinese alligators (Alligator sinensis) was compared with that of shells from eggs with early embryonic death and with the morphology of eggshells from the American alligator (Alligator mississipiensisis). Pieces of shells were examined in the scanning electron microscope. Parameters examined included: numbers of open pores on the outer surfaces, total shell thickness, and thickness of the outer densely calcified and inner mammillary layers. Results indicate that shells from Chinese and American alligator eggs with early embryonic death have a thicker outer densely calcified layer than do shells from hatched eggs or full-term embryos. Also, eggshells from Chinese alligator eggs with dead embryos have fewer open pores on the outer surface than do shells from hatched eggs, as has been reported earlier for the American alligator (Wink et al., '90). © 1994 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052220110
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  • 97
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    Development of craniofacial musculature in Monodelphis domestica (marsupialia, didelphidae) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 149-173 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Development of craniofacial muscles of Monodelphis domestica (Marsupialia, Didelphidae) is described. In a period of 4-6 days all craniofacial muscles in M. domestica progress from myoblast condensation, to striated myofibers that are aligned in the direction of adult muscles and possess multiple, lateral nuclei. This process begins 1 to 2 days before birth and continues during the first few days after birth. Compared to other aspects of cranial development, muscle development in M. domestica is rapid. This rapid and more or less simultaneous emergence of craniofacial muscles differs from the previously described pattern of development of the cranial skeleton in marsupials, which displays a mosaic of acceleration and deceleration of regions and individual elements. Unlike the skeletal system, craniofacial muscles show no evidence of regional specialization during development. M. domestica resembles eutherian mammals in the relatively rapid and more or less simultaneous differentiation of all craniofacial muscles. It differs from eutherian taxa in that most stages of myogenesis occur postnatally, following the onset of function. The timing of the development of muscular and skeletal structures is compared and it is concluded that the relatively early development of muscle is not reflected by any particular acceleration of the differentiation or growth of skeletal structures. Finally, the difficulties in accounting for complex internal arrangements of muscles such as the tongue, given current models of myogenesis are summarized. © 1994 Wiley-Liss, Inc.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052220204
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  • 98
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    Ultrastructure of the ileum epithelium of Melipona quadrifasciata anthidioides (hymenoptera, apidae, meliponinae) (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 191-201 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Study of the epithelial morphology of a stingless bee ileum from the pyloric valve to the last portion of high absorptive cells shows that although the bee ileum is an anatomically undifferentiated tube, four types of epithelial cells along the tube (in addition to the valve cells) indicate physiological differentiation. The anterior end seems to be less active in reabsorption, while the posterior region contains cells with typical morphology of an ion pump and permits conclusions about the mechanisms of absorption in the posterior end of the intestine. © 1994 Wiley-Liss, Inc.
    Additional Material: 15 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052220206
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  • 99
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    Allometry of cetacean forelimb bones (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 215-221 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study examines the allometric scaling relationships of the cetacean humerus, radius, and ulna. Bone lengths and diameters were measured for 20 species of odontocete and three species of mysticete cetaceans, representing eight of the nine extant cetacean families. The scaling of individual bone proportions (bone length vs. cranio-caudal diameter, bone length vs. dorso-ventral diameter), and of individual bone dimensions against estimated body mass, are compared to models of geometric and elastic similarity. The geometric similarity model describes the scaling relationship of bone length vs. cranio-caudal diameter and body mass vs. cranio-caudal diameter for the humerus only; geometric similarity also describes the scaling relationship of body mass vs. bone length for all three bones. None of the scaling relationships fits the elastic similarity model. The scaling relationships of bone length vs. dorso-ventral diameter for all three bones, and bone length vs. cranio-caudal diameter for the radius and ulna, exhibit negative allometry, indicating that large bones are less robust than small bones. Negative allometry of structural support elements has not been previously described for terrestrial mammals or plants. The high relative swimming speeds of small delphinids may generate sufficient stresses to require more robust bones relative to those of larger whales. © 1994 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jmor.1052220208
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  • 100
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    Spermatogenesis in the urodele Amhystoma dumerilii (1994)
    New York, NY : Wiley-Blackwell
    Journal of Morphology 222 (1994), S. 287-299 
    Details
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The male reproductive cycle of this paedomorphic species that occurs only in Lake Pátzcuaro, Michoacán, México, was investigated by documenting changes in germinal cells during the spermatogenic cycle. Cysts of germ cells divide synchronously to complete spermatogenesis during September through December, with the proportion of evacuated cysts or cysts containing spermatozoa increasing during this period. The chromatin changes during prophase I of meiosis reveal the usual leptotene, zygotene, pachytene, and diplotene stages. A basal body at the caudal end of the spermatozoan head connects to the flagellum. After spermiation, empty cysts contain a granular substance. Spermatogenesis in this species follows an annual cycle like other north temperate salamanders, rather than the continuous spermatogenesis of some tropical salamanders. © 1994 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/jmor.1052220306
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