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  • 2000-2004
  • 1995-1999  (2,345)
  • 1990-1994
  • 1920-1924
  • 1995  (2,345)
  • Life and Medical Sciences  (2,263)
  • breast cancer
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  • 2000-2004
  • 1995-1999  (2,345)
  • 1990-1994
  • 1920-1924
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  • 1
    ISSN: 1436-2813
    Keywords: breast cancer ; timing of surgery ; prognosis ; menstrual cycle ; estrogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been suggested that the timing of surgery during periods of unopposed estrogen circulation, when high blood levels of estrogen and low blood levels of progesterone exist, has a deleterious effect on the survival of premenopausal patients with breast cancer. We studied this controversial issue by examining the serum estradiol and progesterone levels of 38 premenopausal patients with primary breast cancer, and by analyzing data on 100 premenopausal patients treated for primary breast cancer. The survival of 31 patients who had undergone initial surgery between days 3 and 12 after their last menstrual period (group E) was compared with that of 69 patients who had undergone surgery between days 0 and 2 or from 13 days after their last menstrual period (group P). The overall survival of group E was significantly worse than that of group P (P=0.049). This difference was especially notable in patients with node-positive tumors or tumors larger than 2 cm in size; however there was no significant difference in disease-free survival between the two groups. On a multivariate analysis, nodal status was the only significant prognostic factor for both overall and disease-free survival. Thus, these findings suggest that unopposed estrogen circulation may be detrimental to the overall survival of premenopausal women with breast cancer.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-2813
    Keywords: aspiration biopsy cytology ; quadruple test ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to investigate the use-fulness of aspiration biopsy cytology (ABC) and other combined tests for the preoperative diagnosis of breast cancer. In an analysis of 599 aspirates of breast tumors, “suspicious” cases were included among the positive, while “borderline” cases were considered to be negative. The sensitivity of ABC was 87.3%, the specificity was 92.3%, and the predictive value of a postive diagnosis was 92.8%. A total of 207 cases of breast cancer were evaluated to determine the diagnostic significance of breast cancer, particularly for tumors less than 2.0 cm by means of a quadruple test including physical examination, mammography (MMG), ultrasonography (US), and ABC. The combined tests of MMG or US, and ABC resulted in a sensitivity of 96.2% and 94.9%, respectively, and were considered to complement each other in the diagnosis of small breast cancer. Surgical biopsy is thus not always necessary in malignant cases that are conclusively diagnosed by the combined quadruple test.
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  • 3
    ISSN: 1436-2813
    Keywords: quality of life (QOL) ; breast cancer ; endocrine therapy ; chemotherapy ; multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, “The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs” (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1436-2813
    Keywords: breast cancer ; hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rare case of sudden hemorrhage caused by breast cancer is herein presented. A 65-year-old woman was admitted to our hospital because of bleeding from her left breast. On physical examination, a continuous hemorrhage accompanied by an open cavity formation was observed in her left breast. She had no history of breast trauma. Her bleeding profile studies and liver function were both normal. In addition, no anticoagulation medication had been administered. The histological findings of the cavity wall indicated invasive ductal carcinoma without skin invasion. After carrying out chemotherapy, a standard radical mastectomy was performed.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cancer immunology immunotherapy 12 (1995), S. 87-94 
    ISSN: 1432-0851
    Keywords: tamoxifen ; breast cancer ; uterine cancer ; estrogen effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tamoxifen, an estrogen antagonist, is widely used as adjuvant therapy in patients with breast cancer. Its efficacy in increasing survival and reducing recurrence rates has been demonstrated in several European and American studies. However, its effects appear to be tissue specific. Tamoxifen exerts an estrogen effect (agonist) on the endometrium, myometrium and vagina. An increase in uterine cancer has been confirmed in several placebo-controlled clinical trials. Due to the widespread use of this drug, it is timely to review the gynecologic effects of tamoxifen.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 77-78 
    ISSN: 1432-1041
    Keywords: Radiation recall ; Tuberculosis therapy ; pyrazinamide ; rifampicin ; isoniazid ; tamoxifen ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of behavioral medicine 18 (1995), S. 377-384 
    ISSN: 1573-3521
    Keywords: breast cancer ; testicular cancer ; gender and cancer prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Participants in this study (N=178) were poorly informed about risk factors, warning signs, and self-examination (SE) practices for two common cancers in young adults, testicular cancer in men and breast cancer in women. Compared to women, men were less likely to know about, see the importance of, or practice SE. We found no relationship between internal locus of control, hypochondriasis, and loneliness, on the one hand, and cancer knowledge and SE, on the other. The best predictors of cancer awareness and SE were fear of developing cancer and self-rated confidence that SE was being done correctly. The results are consistent with a health belief model and self-efficacy theory of health behavior.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-4986
    Keywords: breast cancer ; T-, Tn-specific lectins ; Agaricus bisporus ; Helix pomatia ; Vicia villosa ; antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Sialylated or sulfated derivatives and acrylamide copolymers of blood group T-(Galβ1,3GalNAcα-) and Tn-(GalNAcα) haptens were studied for their interaction with the lectins of peanut (PNA),Agaricus bisporus-(ABA),Helix pomatia-(HPA) andVicia villosa B4-(VVA), using asialo Cowper's gland mucin (ACGM), which contains both T and Tn epitopes, as the coating substrate in enzyme linked lectin assay. Both T and Tn copolymers (∼40 haptens) showed high affinity and strict specificity; although the T-copolymer at 0.05–0.07 µm concentration caused 50% inhibition of interaction of either PNA or ABA with ACGM, there was little inhibition of the HPA and VVA interactions at over 100 times that concentration. The Tn-copolymer at 0.02–0.05 µm inhibited HPA or VVA interaction with ACGM by 50% but gave virtually no inhibition of PNA and ABA binding. Sialyl, sulfate or methyl group substitution on C-6 of GalNAc of the T-haptene did not prevent interaction with PNA but almost abolished interaction with ABA. In contrast, sialyl or sulfate group on C-6 and sulfate on C-3 of Gal in Galβ1,3GalNAcα- inhibited almost completely the interaction of PNA with ACGM but had only a slight effect on the interaction of ABA; C-6 substitution with either sialic acid or sulfate on GalNAcα- almost abolished the interaction of both HPA and VVA with ACGM. Preliminary studies revealed a significant depression in the serum level of anti-T (two to three-fold decrease) and anti-Tn (∼ two-fold decrease) antibodies in breast cancer compared with normal control subjects when the acrylamide T- and Tn-copolymers were used as coating substrates in enzyme linked immunoassays.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-0646
    Keywords: gossypol ; gossypolone ; Schiffs base derivatives ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Preclinical and clinical studies have pointed to the antitumor potential of the naturally occurring polyphenolic binaphthyl dialdehyde, gossypol, as well as its purified (−,+) enantiomers. To explore further the antitumor properties of this multifunctional agent, we synthesized several reactive derivatives including the (−,+) enantiomers of gossypolone and four different gossypol Schiffs bases (AR1, AR2, AR3, AR4). The biological activities of these new agents were screened by measuring theirin vitro antiproliferative activity against malignant (MCF-7, MCF-7/adr) or immortalized (HBL-100) human breast epithelial cell lines. Racemic gossypolone showed relatively uniform antiproliferative activity against all of the breast epithelial cell lines with 3- to 5-fold less activity than (-)-gossypol against MCF-7 and MCF-7/adr cells. Of interest, the relative antitumor potency of purified gossypolone enantiomers was reverse that of gossypol enantiomers, since (+)-gossypolone showed up to 3-fold greater inhibition of MCF-7 culture growth than (-)-gossypolone. Of the Schiff's base derivatives only AR3 with its isopropyl amine substituent demonstrated cytotoxic activity comparable to that of (-)-gossypol; derivatives with ethyl, propyl, or butyl amine substituents (AR1, AR2, AR4) had little growth inhibitory activity at culture concentrations up to 25 μM. AR3 activity was greatest against HBL-100 and MCF-7 cells [MCF-7 IC50 values: AR3=0.9 μM, (-)-gossypol=2.3 μM]; unlike (-)-gossypol, however, AR3 showed substantially reduced activity against the multidrug-resistant subline, MCF-7/adr. These structure-activity comparisons suggest that isolation of (−,+)-enantiomers of AR3 and additional chemical modifications including the synthesis of an isopropyl amine Schiff's base of gossypolone will likely yield a newer generation of gossypol analogues with enhanced anticancer potential.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-0646
    Keywords: paclitaxel ; breast cancer ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Paclitaxel (Taxol®) is a natural product with a broad spectrum of activity against various solid tumors. This report includes nineteen patients with advanced breast cancer who have not previously received chemotherapy for metastatic disease. Fifteen patients had received adjuvant chemotherapy, eight of which were doxorubicin based. Patients were treated with 135 mg/m2 over 24 hours by continuous infusion given every 21 days. There were 2 complete and 4 partial responses for an objective response rate of 32% (95% C.I.: 14%, 57%) and eight patients or 42% with stable disease. Three of eight patients (38%) who had received adjuvant doxorubicin did respond to paclitaxel. Responses occurred in lung, liver, and soft tissue. The primary toxicity was hematologic with 13 hospitalizations for febrile neutropenia in 180 cycles (7%). Paclitaxel has moderate activity in a small number of patients with metastatic breast cancer at the dose of 135 mg/m2 over 24 hours in this study.
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  • 11
    ISSN: 1573-0646
    Keywords: Epidermal Growth Factor ; vinorelbine ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Epidermal Growth Factor (EGF) is a mitogenic peptide that binds to surface membrane receptors (EGFR) of breast cancer cells. After binding, secondary transmitter molecules are activated by tyrosine phosphorylation of the intracellular receptor domaine. The activity of the EGF/EGFR system can be modulated by a variety of chemically unrelated compounds including cytostatic agents. The purpose of our present study was to determine the effects of vinorelbine, a novel semisynthetic vinca alkaloid on EGF receptor binding on human breast cancer cells. We have found that MDA-231 and MDA-468 cells bind substantially more [125I]-EGF after preincubation with vinorelbine. This effect was concentration- and time-dependent reaching a maximum at 100 ng/ml and 24 h incubation. Subsequent experiments showed an increase in the rate of EGF binding as well as maximal binding capacity. Scatchard analysis of binding experiments under equilibrium conditions indicated that this was mainly due to an increase in the number of apparent EGF binding sites. Modulation of EGF receptor binding by vinorelbine was not detectable when isolated membranes were used indicating that intact cytoplasmatic mechanisms are required for the upregulation of EGF receptors.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Cancer causes & control 6 (1995), S. 75-82 
    ISSN: 1573-7225
    Keywords: Abortion ; breast cancer ; international comparison ; miscarriage ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidemiologic studies have been inconsistent in suggesting an association between abortion and breast cancer risk. Whether the protection provided by a full-term pregnancy also results from a short-term pregnancy or whether a prematurely terminated pregnancy could increase the risk of breast cancer is unclear. Data from a large, international collaborative study were used to evaluate the association between abortions, whether spontaneous or induced, and breast cancer risk. The data from seven countries included 3,958 breast cancer cases and 11,538 hospital controls with information on abortion history obtained through interviews. Compared with nulliparous women with no abortion (baseline), the odds ratios (OR) and 95 percent confidence intervals (CI) were: for nulliparous women with a history of prior abortion, 0,86 (CI=0.68–1.08); for parous women with no history of abortion, 0.63 (CI=0.57–0.69); for parous women with abortion before first birth, 0.82 (CI=0.69–0.97); and, for parous women with abortion only after first birth, 0.70 (CI=0.63–0.79). When restricting analysis to parous women, those with a history of abortion exhibited an elevated OR suggesting a 29 percent risk increase if the incomplete pregnancy occurred before first birth (CI=1.16–1.36) and an 11 percent risk increase for abortion only after first birth (CI=1.02–1.20) compared with women without such history. The associations observed were stronger among the youngest women. These results do not support a large overall association between abortion and breast cancer risk.
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  • 13
    ISSN: 1573-7276
    Keywords: breast cancer ; extracellular matrix molecules ; integrins ; metastasis ; surgical trauma ; xenograft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate critically the merit of utilizing a wound model for growing human tumors, a series of increasingly difficult human tumor types were tested for growth at sites of trauma in athymic nude mice. In vitro tumor lines as well as fresh tumors from the breast, colon, rectum, lung, and a metastasis from an unknown primary were intraperitoneally injected into mice subjected to intra-abdominal organ injury. Successful xenografts were obtained from nine of 10 cell lines and 14 of 24 fresh tumors. The latter included five of six (83%) colon cancers, one lung tumor, metastatic tumor of unknown primary, three of four (75%) metastatic breast cancers and four of six (67%) estrogen receptor (ER)-negative breast primary tumors. Six ER-positive breast tumors tested failed to grow in mice without estrogen supplementation. Xenografts from two breast, two colon and the lung cancers formed spontaneous metastases and all xenografts tested were able to yield serial transplants in the surgical wound model. Histologically, all xenografts and their metastases were identical to their respective donor tumors. Transplantability in mice without exogenous estrogen supplementation was linked to the absence of estrogen and progesterone receptors in breast tumors. Transplantability of the cell lines was associated with the expression of cell surface receptors for fibronectin and hyaluronic acid. Receptors for other extracellular matrix components, namely, laminin, vitronectin, collagen, fibrinogen or von Willebrand factor were not associated with transplantability. These results demonstrate that a large proportion of human tumors, including the breast tumors, can be successfully xenografted into athymic mice by providing them with a healing wound environment, and that such xenografts grown at ectopic sites exhibit metastatic ability.
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  • 14
    ISSN: 1573-7276
    Keywords: breast cancer ; histocompatibility antigens ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of the major histocompatibility (MHC) class I and class II antigens was studied by immunohistochemistry in a series of 70 primary breast carcinomas and in nodal metastases. In particular, the expression of class I (HLA A-B-C) and class II (DP, DQ and DR) molecules was compared in: a) primary breast cancers devoid of nodal metastases (n = 36) and tumors exhibiting metastatic deposits (n = 34) at the time of surgery, and b) primary breast carcinomas and their corresponding synchronous axillary nodal metastases. Reduced or absent HLA A-B-C antigen expression was seen in approximately 54.3% of primary breast carcinomas, whereas a partial or complete induction of class II products was observed in 18.5% (DQ), 30% (DP) or 48.5% (DR) of the same cases. An almost complete overlap of antigen expression was observed in breast tumors in which no metastases were found by histological examination of axillary nodes and in neoplasms showing histologically-diagnosed synchronous metastases. The reactivity for class I and class II antigens in nodal metastases roughly paralleled that exhibited by corresponding primary tumors. A discordant expression was seen in 11 cases (32%) stained for HLA A-B-C and in 8 (24%), 7 (21%) and 6 (18%) cases assayed for DP, DQ and DR products, respectively. When a discordant expression was detected, either decreased or increased staining patterns were observed in metastases. The finding of overlapping MHC antigenic profiles in the majority of primary breast tumors and nodal metastases casts doubts on the hypothesis that loss of MHC antigens can play an important role in the seeding and growth of metastatic breast carcinoma cells.
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  • 15
    ISSN: 1573-7276
    Keywords: antigen shedding ; breast cancer ; membrane vesicles ; tumor-associated antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small dimensions, the same technique was not applicable to vesicles. For these structures dot-blot analysis and immunoelectron microscopy (IEM) were employed. When applicable, both cell membranes and membrane vesicles were immunoprecipitated and the precipitate (IP) was analyzed by SDS-PAGE. Cells of both lines expressed HLA class I antigens, epithelial cytokeratins, β1 integrins, CEA and the glycoprotein detected by mAb 19.9, but only MCF-7 cells expressed Lewis Y, episialin and globo-H antigens and only 8701-BC cells expressed folate receptor. Membrane vesicles of both cell lines appeared to be rich in β1, α3 and α5 integrin chains, expressed HLA class I antigens and carried most of the plasma membrane antigens found in the cell membranes. Overall we have analyzed 17 antigens on the two cell lines and on their vesicles. The results obtained for cells (IF and IP) and those for vesicles (dot-blot and IP) were generally concordantly positive or concordantly negative. We obtained a total of 26 clearly concordant combinations on 34 analyses. In three cases we found discordant results, whereas in the remaining combinations we observed slight reactivity and we found difficulties in determining concordance. Discordant results concerned the expression of the following antigens: folate receptors, which were clearly expressed in 8701-BC cells but not detected by dot-blot analysis or IEM on their shed membrane vesicles; neu (c-erb-B2) receptor found in MCF-7 cell membranes but not in their vesicles; and the globo-H antigen recognized by mAb MBr1, detected at low levels on 8701-BC plasma membranes but undetectable on their membrane vesicles. Like vesicles shed in vitro by cultured cells, the vesicles shed in vivo by human breast carcinoma cells could be tagged with several antibodies against tumor-associated antigens. The vesicles shed in vivo were found in association with a fiber network. Some of the fibers had the characteristic fibrin periodicity. These data suggest that tumor markers detected in the circulation of carcinoma patients, at least in part, are carried by shed membrane vesicles. Moreover the observation that membrane vesicles carry both tumor-associated antigens and HLA class I molecules indicate that these structures could in principle present antigens to the immune system. Together with our previous demonstration that membrane vesicles shed by breast carcinoma cells contain TGF-β, these results suggest an important role for vesicles in the immunological escape of these cells. The presence in membrane vesicles of integrins, together with the previous observation that they are rich in gelatinolytic activities, also points to a possible role of these structures in the metastatic behavior of tumor cells.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 23 (1995), S. 15-21 
    ISSN: 1573-7373
    Keywords: breast cancer ; leptomeningeal carcinomatosis ; macrophage ; T cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five percent of patients dying with breast cancer have leptomeningeal metastases (LM) but current therapy is of only marginal benefit. Therefore, an experimental model of LM from breast cancer was developed to facilitate the development of novel therapies. Cell suspensions of 13762 MAT BIII rat mammary carcinoma cells are injected into the cisterna magna of adult, female Fischer 344 rats under general anesthesia. 10–12 days after the injection of 2×105 viable cells, animals develop neurologic signs, including ataxia, paralysis and spontaneous rotation. Histologically, tumor cells can be seen in the subarachnoid space over the surface of the brain and spinal cord and within the ventricles. Tumor cells do not invade the brain parenchyma. Collections of tumor cells are extensively infiltrated by macrophages and CD8-positive (suppressor/cytotoxic) T cells, but by few CD4-positive (helper) T cells. MAT BIII cells therefore provide a model of LM from breast cancer with a reproducible clinical course and histologic features. The tumor elicits a cellular immune response and can be useful in exploring biologic therapies for leptomeningeal metastases.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 23 (1995), S. 121-134 
    ISSN: 1573-7373
    Keywords: breast cancer ; spinal metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions Metastases to the spine is a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life due to troublesome back pain and neurologic morbidity. It is not uncommon for spinal metastases to be an early and predominant manifestation of the patients systemic disease process. Although the breast cancer must be considered to be advanced, these patients will frequently have a reasonable functional status at the time of diagnosis of the spinal metastases. Accordingly, an aggressive approach of management should be considered in such patients so as to potentially achieve the most effective palliation. In the setting of breast cancer metastatic to the spine, radiation/systemic steroidal therapy remains the first line of management. The principle exception favoring primary surgical management is roentgenographic evidence of spinal instability related to the vertebral involvement by the metastatic process. The surgical team must also remain ready to intervene early with surgical decompression and spinal stabilization when any neurologic deterioration occurs during radiation therapy. When surgery is indicated, the anterior transthoracic approach to spinal metastases is an effective means of palliating these breast cancer patients. A team approach involving the spinal surgeon, thoracic surgeon and anesthesiologist optimizes the care of the patient requiring thoracic spinal decompression of metastatic disease. Involvement of the thoracic surgeon in these patients care can result in expeditious thoracic exposure of the pathologic area of concern and valuable contribution to the post-operative care of these unfortunate patients.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 24 (1995), S. 299-301 
    ISSN: 1573-7373
    Keywords: megace ; brain metastases ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 56 year old women was treated with megestrol acetate (Megace) 40 mg p.o. q.i.d. for her cerebellar metastasis of primary adenocarcinoma of the breast. She had previously undergone two surgical resections of her brain metastasis, and a course of radiotherapy. After failing to tolerate tamoxifen therapy, she received Megace, with marked improvement in her cerebellar tumor on CT scans. Despite good control of her brain tumor with Megace, she developed progressive neurological symptoms thought to be due to meningeal carcinomatosis, and died two years after initiating Megace therapy. We conclude that Megace could potentially be beneficial in some patients with brain metastases from adenocarcinoma of the breast.
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  • 19
    ISSN: 1573-7373
    Keywords: optic neuropathy ; paclitaxel ; breast cancer ; visual evoked potentials ; neurotoxicity ; peripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The case of a 63 year-old woman affected by advanced breast cancer is reported. Chemotherapy with paclitaxel (200 mg/m2) and doxorubicin (60 mg/m2) every three weeks was given for 8 cycles. The patient progressively developed a sensory-motor neuropathy of axonal type. After the 6th chemotherapy cycle the patient complained of subjective visual symptoms without a relevant reduction of visual acuity. Visual evoked potentials (VEPs) showed an important reduction of the amplitude of the P100 component with a less pronounced delay in latency. Electroretinic responses were normal. These findings suggest an optic neuropathy, confirming previous reports of the occurrence of optic nerve involvement in course of paclitaxel chemotherapy. The role of VEP assessment in course of paclitaxel chemotherapy is discussed comparing clinical and neurophysiological findings in this case with three previously reported cases.
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  • 20
    ISSN: 1573-7225
    Keywords: Age at first birth ; breast cancer ; females ; parity ; reproductive factors ; Sweden
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: We set out to detect a transient increase in risk of breast cancer following childbirth, the existence of which has been postulated, but for which empirical evidence is contradictory. Breast cancers and births occurring among the cohort of Swedish women born after 1939 were linked, yielding 3,439 cases and 25,140 age-matched controls with at least two children. Within three years of their last childbirth, women had an estimated rate of breast cancer of 1.21 (95 percent confidence interval [CI]=1.02–1.44) times that of women whose last birth was 10 or more years earlier, after adjustment for parity and age at first birth. Further analyses suggested that this effect reflected, in part, a small transient increase in breast cancer risk that lasts for about three years following completed pregnancy. The effect of age at first birth on breast cancer risk appears to be confounded by time since last birth; the parity-adjusted rate ratio for having a first birth at age 35 years or more compared with under 20 years is reduced from 1.72 (CI=1.14–2.58) to 1.36 (CI=0.88–2.09) on additional adjustment for time since last birth. A transient increase in breast cancer risk after childbirth thus appears to account for part of the effect of age at first birth on breast cancer risk.
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  • 21
    ISSN: 1573-7217
    Keywords: steroid receptors ; immunocytochemistry ; breast cancer ; fine needle aspiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For 56 cases of carcinoma of the breast, results of the immunocytochemical assay for estrogen and progesterone receptors performed on preoperative fine-needle aspirates were compared with those obtained on scraping material from the same tumors. The value and usefulness of this last analysis was demonstrated in a previous study. The level of agreement between the two cytological techniques was assessed by the k statistic. A high level of agreement was found, with k values of 0.909 and 0.889 for estrogen and progesterone receptors, respectively. The results reported here revealed the reliability of steroid receptor determination on fine-needle aspiration biopsies, provided that sufficient cellularity was available. This technique can replace the open biopsy procedure, inasmuch as it represents a rapid, almost painless, and easily repeated method for the assessment of the receptor status, and is useful for treatment decisions at any time during the course of the disease.
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  • 22
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 34 (1995), S. 77-83 
    ISSN: 1573-7217
    Keywords: breast cancer ; elderly ; tamoxifen ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the efficacy of tamoxifen as primary treatment for elderly breast cancer patients with locoregional disease, the medical records of 85 patients of 75 years and older were reviewed. The median follow-up was 28 months (range 3–97 mo). Complete remission occurred in twelve (14.1%) patients. All of these patients remained in remission until death or closing date of the study. Twenty (23.5%) patients responded with a partial remission; 5 of them subsequently developed tumor progression. Thirteen (15.3%) patients developed initial tumor progression and 39 (45.9%) had disease stabilisation. Nineteen of this latter group subsequently developed tumor progression. Out of 37 (43.5%) patients with tumor progression, 14 patients were salvaged by surgery (n = 13) or radiotherapy (n = 1). Until the closing date of the study, disease could not be controlled by secondary treatment in 12 patients who subsequently died of breast cancer. Twenty-two of the 37 patients were unfit for surgical treatment at progression, of whom 14 were operable at diagnosis. The actuarial 5-year observed survival rate was 40% for the whole patient group. Conclusions: Although some patients (14.1%) managed to maintain a long lasting complete remission, caution should be preserved in using tamoxifen as first-line treatment, because of the high risk of treatment failures. As long as factors can not be identified to predict which subgroups of patients will respond to tamoxifen with a remission lasting for their life-time, tamoxifen may only provide an acceptable alternative for elderly breast cancer patients who are too frail or are unwilling to undergo surgery or radiotherapy. For elderly patients in good physical condition, primary treatment by tamoxifen only delays definitive surgical treatment.
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  • 23
    ISSN: 1573-7217
    Keywords: breast cancer ; oral etoposide ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a phase II study, 27 patients with metastatic breast cancer were treated with oral etoposide as second-line chemotherapy at a dose of 50 mg/m2/day for 21 days, which courses were repeated every 4 weeks. Twenty-one patients were evaluable for response, and twenty-five for toxicity. In two (10%) patients a partial response was observed with a duration of 60 and 122 weeks respectively, and seven patients (33%) showed stable disease. Gastrointestinal toxicity was usually mild, though relatively frequent. Anemia grade II and III was observed in 20% of all courses (〈 10% of all measurements), and leukopenia grade III and IV was observed in 22% of all courses (〈 10% of all measurements). There was one toxic death. Reviewing the literature we calculated a response rate of intravenous etoposide treatment of 8% in 276 patients with metastatic breast cancer from 7 studies (response rates ranging between 0–14%), while (chronic) oral treatment caused a response rate of 19% in 145 patients from 8 different studies (response rates ranging between 0–35%).
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  • 24
    ISSN: 1573-7217
    Keywords: chromosomes ; breast cancer ; chromosome microdissection ; physical mapping
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.
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  • 25
    ISSN: 1573-7217
    Keywords: breast cancer ; dehydroepiandrosterone ; DHEA-sulfatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dehydroepiandrosterone (DHEA) has been shown to affect the growth of mammary carcinomas bothin vitro andin vivo. In humans, very high levels of DHEA and/or dehydroepiandrosterone sulfate (DHEAS) have been found in breast tissues and secretions, and epidemiological studies suggest a role of these steroids in the modulation of breast cancer growth. An uptake from plasma and a transformation from precursors can be both postulated, but the main source of the adrenal C19 steroids found within the breast is debated. Attempting to clarify this point, in ten patients undergoing surgery for breast cancer we studied: a) DHEAS and DHEA concentrations in tumor tissue; b) the differences between DHEAS (or DHEA) concentration in peripheral venous plasma and that draining the affected breast, that we assume to reflect the arteriovenous gradient of these steroids; c) DHEA sulfatase activity in tumor tissue. Results show that DHEA sulfatase activity is not related to DHEAS or DHEA concentrations in breast cancer tissue. A negative DHEA plasma gradient across the breast is unveiled, whereas DHEAS levels are not different in blood supplying and draining the breast with cancer. The DHEA plasma gradient across the breast is positively related to DHEA concentration in tumor tissue. Data are consistent with the hypothesis that the plasma source contributes remarkably to DHEA found within breast cancer tissue.
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  • 26
    ISSN: 1573-7217
    Keywords: breast cancer ; steroidal antiestrogen ; pure antiestrogen ; DMBA tumors ; estradiol ; estrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, compounds having pure antiestrogenic activity have become available. In this study, we examined the activity of the new steroidal antiestrogen EM-170 (N-n-butyl, N-methyl-11-(16′α-chloro-3′,17′α-dihydroxy-estra-1′,3′,5′-(10′)-trien-7′α-yl) undecanamide) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma stimulated by treatment with estrone (E1), a steroid known to play an important role as precursor of 17β-estradiol (E2), especially in postmenopausal women. Twenty-five days after ovariectomy (OVX), tumor volume in control OVX animals decreased to 51.4 ± 11% of the initial volume; treatment with E1, administered by Silastic implants, stimulated tumor growth to 179 ± 21%. Treatment with the antiestrogen EM-170 at a dose of 200 µg (twice daily) not only completely reversed the stimulatory effect of E1, but also inhibited tumor growth to 30.5 ± 9.6%, an effect that is 41% (P 〈 0.01 vs OVX control) greater than that of ovariectomy alone. At a relatively low dose of 40 µg (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 µg, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in the DMBA-induced mammary tumors, an effect that is in agreement with the marked reduction caused by the same treatment on tumor estradiol (E2) levels in E1-treated OVX animals. The present data show that the new steroidal antiestrogen EM-170 exerts a potent inhibitory effectin vivo on E1-stimulated growth of DMBA-induced mammary tumors, an effect that is probably mediated by both its antiestrogenic activity at the receptor level and its inhibitory effect on 17β-HSD, thus inhibiting local E2 formation and facilitating the action of the antiestrogen at the receptor level.
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  • 27
    ISSN: 1573-7217
    Keywords: breast cancer ; prognostic factors ; genetic evolution ; DNA flow cytometry ; age at diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the ‘aggressive’ phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.
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  • 28
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 34 (1995), S. 55-61 
    ISSN: 1573-7217
    Keywords: breast cancer ; fat distribution ; obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The association between body fat distribution and breast cancer risk was studied in 5923 pre- and 3568 postmenopausal women, participating in a breast cancer screening project (the DOM-project in Utrecht, the Netherlands). Cases were fifty six premenopausal women and thirty eight postmenopausal women with breast cancer detected at screening or afterwards. Controls were women participating in the breast cancer screening project without breast cancer. Waist- and hip circumferences, height and weight were measured at screening, before diagnosis of breast cancer. In postmenopausal women the estimated relative risk of women in the upper tertile of waist/hip ratio compared with women in the lower tertile was 1.89 (95% CI 0.80–4.48), (test for trend p = 0.11). The estimated relative risk of women in the upper tertile of waist circumference compared with women in the lower tertile was 2.86 (95% CI I 1.12–7.32), (test for trend p = 0.08). The association between waist circumference and breast cancer was stronger than the association between any of the other anthropometric variables and breast cancer. In premenopausal women the association between fat distribution and breast cancer was equivocal.
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  • 29
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 34 (1995), S. 85-92 
    ISSN: 1573-7217
    Keywords: breast cancer ; signal transduction ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 30
    ISSN: 1573-7217
    Keywords: breast cancer ; c-erbB-2 ; HER-2/neu ; growth factors ; growth factor receptors ; transfection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ac-erbB-2 expression vector was transfected into the estrogen receptor positive (ER+) MCF-7 human breast cancer cell line to determine if overexpression of this transmembrane tyrosine kinase could increase the malignant phenotype of this cell line. Loss of transfectedc-erbB-2 expression was observed when cells were carried in medium containing estrogen. Homogeneous populations stably overexpressing levels of the 185 kDac-erbB-2 observed in the SKBR-3 a breast cancer cell line which overexpressesc-erbB-2 as a result of gene amplification could be obtained by continually maintaining the transfected cell lines in estrogen-free conditions. Levels of constitutively activatedc-erbB-2 varied among clonal isolates. Whereas some over-expressing lines did acquire the ability to form transient tumor nodules in ovariectomized nude mice without estrogen supplementation, as well as in mice that received the antiestrogen tamoxifen, one cell line that exhibited the highest levels of constitutively activatedc-erbB-2 was able to form static tumors of a larger size under both conditions. This same cell line formed progressively growing tumors in estrogen-supplemented mice that were much larger than observed in mice injected with control cell lines, and also showed reduced sensitivity to antiestrogensin vitro, but it continued to have a low metastatic phenotype. These results suggest that signal transduction mediated by thec-erbB-2 tyrosine kinase can partially overcome the estrogen dependence of ER+ breast cancer cells for growth and thatc-erbB-2 overexpression confers a selective advantage to such cells in the absence of estrogen.
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  • 31
    ISSN: 1573-7217
    Keywords: GM-CSF ; cutaneous reactions ; immune phenomena ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The application of recombinant colony stimulating factors for chemotherapy induced granulocytopenia is becoming common in clinical oncology. Here we report on localized cutaneous side effects after subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) in 11 patients with breast cancer receiving cytostatic treatment. Seven patients suffering from inflammatory breast cancer received cytostatic chemotherapy with mitoxantrone/cyclophosphamide, whereas four patients suffering from noninflammatory breast cancer received high-dose epirubicin/cyclophosphamide, respectively. rh GM-CSF was applicated subcutaneously in a dose of 5 µg/kg/d for at least ten days. In all patients, sharply demarked, maculous itching and burning erythemas restricted to the injection sites occured after three to four injections of rh GM-CSF. These eruptions cleared within 2 to 3 weeks, but reappeared after reexposure to rh GM-CSF. In contrast to previous sporadic reports, no generalized erythemas were observed. Because of this unexpected and subjectively intolerable side effect, rh GM-CSF administration had to be interrupted in all patients. Histopathological findings revealed skin infiltration with lymphocytes, monocytes/macrophages, neutrophils, and occasionally eosinophils, respectively. Since GM-CSF is known to alter immune functions, it seems likely that the eruptions were at least in part due to local immune reactions.
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  • 32
    ISSN: 1573-7217
    Keywords: biochemistry ; breast cancer ; estrogen receptors ; immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Over the last few years, estrogen receptor (ER) determination by immunohistochemistry (ER-ICA) has been extensively used, but it still remains to be established whether this method can replace the standard biochemical technique using dextran-coated charcoal (ERDCC). Patients and methods: ER were determined by both the dextran-coated charcoal (DCC) method and immunohistochemistry (ICA) in 699 patients with primary breast cancer; other parameters (age, pathological T-pT- and nodal status -pN-, progesterone receptors by DCC, proliferative index by ICA) were also recorded. The ‘best’ cut-off for ERICA was evaluated by means of Receiver Operating Characteristics (R.O.C.) analysis; logistic regression analysis was used to find adequate ‘weights’ for stain intensity. Results and conclusions: A significant correlation was found between the two methods (p 〈 0.001). R.O.C. analysis revealed that the ‘best’ cut-off for the ERICA score was 45% (sensitivity 0.810, specificity 0.804). Logistic regression analysis showed that an ERICA score which also considers staining intensity does not add any useful information concerning ER content in breast cancers.
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  • 33
    ISSN: 1573-7217
    Keywords: breast cancer ; DNA ploidy ; erbB-2(HER-2/neu) ; intraductal carcinoma ; ductal carcinomain situ
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ductal carcinomain situ (intraductal carcinoma) of the breast is a commonly recognized and curable clinical entity. Patients with intraductal carcinoma are at risk to develop invasive breast cancer presumably due to a transition from the noninvasive to the invasive phase of growth. Primary breast malignancies commonly display bothin situ and invasive phases of growth in the same tumor. In the current study, DNA content and alterations in the erbB-2 (HER-2/neu) oncogene product were examined simultaneously in both growth phases of primary breast cancers by image analysis. DNA content in the intraductal and invasive components of primary breast cancers were virtually identical (r = 0.979, p 〈 0.001). Quantitative image analysis was used to measure erbB-2 expression and categories of expression were related to copy number of the erbB-2 gene. Expression of erbB-2 was similar in both growth phases and implies identity of the erbB-2 genotype. The identity of DNA content suggests that the noninvasive and invasive phases within a single breast cancer are highly related. It is likely that erbB-2 gene number remains the same during progression from intraductal to invasive disease.
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  • 34
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; breast cancer ; endocrine therapy ; NMR spectroscopy ; plasma lipids ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the1H magnetic resonance spectrum (500 MHz) were analyzed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition,13C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels. The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the13C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs. 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses. In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.
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  • 35
    ISSN: 1573-7217
    Keywords: vinorelbine ; topotecan ; camptothecin 11 ; breast cancer ; topoisomerase 1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vinorelbine is a semi-synthetic vinca alkaloid which was initially developed in France in the 1980's. Due to its unique structure it is considerably less neurotoxic than vincristine. Several phase II studies have shown that vinorelbine is active in metastatic breast cancer therapy with response rates of 20–30% in pretreated and 40–50% in nonpretreated patients respectively. Higher response rates have been noted when vinorelbine is used in combination regimens. The main dose-limiting toxicity seen with this agent has been neutropenia; neurotoxicity manifest as symptomatic paresthesia can be seen in 10% of treated patients. Oral and implantable forms of the drug have also been investigated. The topoisomerase 1 inhibitors topotecan and camptothecin 11 (CPT-11) have been less extensively evaluated in breast cancer therapy. Preclinical studies have indicated that both of these agents are active against breast cancer and some responses have been seen in phase 1 trials of topotecan. An 8% response rate was noted in a phase II trial of CPT-11 in patients with pretreated metastatic breast cancer. Further phase II trials are ongoing at present with both agents.
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  • 36
    ISSN: 1573-7217
    Keywords: breast cancer ; ornithine decarboxylase ; polyamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the direct influence of the polyamine (PA) pathway on breast cancer phenotype, we employed a transfection approach to induce overexpression of the PA biosynthetic enzyme ornithine decarboxylase (ODC) in the hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overexpression of ODC resulted in a consistent but modest increase in [3H]thymidine incorporation into DNA which was similar in the presence and absence of 17-β-estradiol, TGF-α, and IGF-I. In the presence of serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was inconsistent, possibly as a result of subtle differences in culture conditions. Overall, our results support the hypothesis that activation of the PA biosynthetic pathway may confer a growth advantage to breast cancer cells.
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  • 37
    ISSN: 1573-7217
    Keywords: breast cancer ; fat distribution ; obesity ; prognosis ; postmenopausal ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness. No significant differences in survival time between more obese (Quetelet's index ≥ 26 kg/m2) and leaner (Quetelet's index 〈 26 kg/m2) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors. The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.
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  • 38
    ISSN: 1573-7217
    Keywords: androgens ; pure antiestrogen ; breast cancer ; estrone ; 17β-estradiol ; 17β-hydroxysteroid dehydrogenase ; medroxyprogesterone acetate ; intracrinology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Estrogens are well known to play a predominant role in promoting the growth of DMBA-induced mammary tumors in the rat. Estrone (E1), a steroid having weak estrogenic activity, is one of most important estrogens in post-menopausal women, where it is converted into the potent estrogen estradiol (E2) by 17β-hydroxysteroid dehydrogenase (17β-HSD) in many peripheral tissues, including the mammary gland. In this report, we have studied the effect of a new antiestrogen (EM-219) (N-butyl, N-methyl-11-(3′, 17′β-dihydroxy-17′α-ethinylestra-1′3′5′(10′), 14′-tetraen-7′α-yl) undecanamide) on E1-stimulated growth of DMBA-induced mammary tumors and compared its effect with that of medroxyprogesterone acetate (MPA) alone or in combination. After 18 days, ovariectomy (OVX) reduced total tumor area to 29.6 ± 7.1% of the original size, while E1 (1.0 µg, twice daily) caused a 139 ± 21% increase in tumor size in OVX animals. MPA (1.5 mg, twice daily) partially reversed the stimulatory effect of E1 to 66.0 ± 9.0%, while the antiestrogen EM-219 (40 µg, twice daily) decreased tumor size to 70.0 ± 10%. Combination of these two compounds led to a further inhibition of tumor size to 30.7 ± 7.4% of the value found in OVX animals treated with E1. Tumor E2 levels decreased from 1688 ± 155 pmoles/kg tissue in OVX animals receiving E1 to 709 ± 92, 1347 ± 98, and 184 ± 11 pmoles/kg tissue in MPA-, EM-219-, and MPA + EM-219-treated OVX-E1 animals, respectively. Treatment of OVX animals with E1 increased by 69% the reductive activity of 17β-hydroxysteroid dehydrogenase (17β-HSD) while MPA abolished completely this effect of E1. In the oxidative direction, treatment with E1, E1 + MPA, or E1 + EM-219 had minimal or no significant effect on the activity of 17β-HSD (vs OVX), while the combined treatment with MPA + EM-219 induced a 2-fold increase in 17β-HSD activity, thus leading to an increased conversion of E2 into E1. The present data show that combination of the pure antiestrogen EM-219 with MPA exerts a greater reduction in DMBA-induced mammary tumor growth and intratumoral E2 levels stimulated by E1 than either compound used alone. This interactive effect of the antiestrogen and MPA could at least partially be related to the increased inactivation of E2 into E1. The present data suggest that such a combination could be a useful approach for the treatment of breast cancer, especially in post-menopausal women.
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  • 39
    ISSN: 1573-7217
    Keywords: alpha-linolenic acid ; breast cancer ; cell proliferation ; fatty acids ; lipid hydroperoxides ; Vitamin E
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epidemiological studies suggest a causal relationship of dietary polyunsaturated fatty acids (PUFA's) with the morbidity and mortality from breast cancer. In order to reveal possible underlying mechanisms of these findings, we studied the influence of n-3 and n-6 PUFA's in comparison to oleic acid on the proliferation of well characterized estrogen dependent (MCF-7, ZR-75, T-47-D) and estrogen independent (MDA-MB-231, HBL-100) breast cancer cells in culture. The cell growth inhibitory effect was related to the formation of lipid peroxidation products. Normal human skin fibroblasts served as a control. In fibroblasts, the addition of 20 µg/ml of exogenous fatty acids either had no effect or caused an insignificant increase of proliferation. Similar results were obtained with MCF-7 cells. In all other breast cancer cell types, n-3 long-chain PUFA's, eicosapentaenoic and docosahexaenoic acids, were the most effective fatty acids in arresting the cell growth. Alpha-linolenic and gamma-linolenic acid exerted a variable effect on cell proliferation depending on the cell line investigated. Oleic acid significantly stimulated the proliferation of hormone-independent breast cancer cells while it had no effect on the proliferation of hormone-dependent cells. Viability studies by trypan blue excretion indicated that the arrest in cell growth was not due to major cytotoxic effects. The addition of PUFA's to breast cancer cells caused a significant increase in the formation of conjugated dienes and lipid hydroperoxides in the cellular lipids; their content was significantly correlated with the capacity of arresting cell growth. In contrast, the addition of PUFA's to fibroblasts did not increase lipid hydroperoxide formation. The addition of Vitamin E to cancer cells at a concentration of 10 µM to the PUFA-supplemented medium almost completely restored cell growth. Our data indicate that PUFA's significantly interfere with cell proliferation of breast cancer cellsin vitro due to the formation of oxidation products. In addition to that, there must be other factors involved, most probably related to the differential metabolism of PUFA's in tumor cells. Our findings may have some impact on treatment and prevention of breast cancer.
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  • 40
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 34 (1995), S. 279-287 
    ISSN: 1573-7217
    Keywords: breast cancer ; timing of surgery ; premenopausal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. In 1989 it was suggested that the timing of surgery during follicular or corpus luteum phase of the menstrual cycle could substantially influence the survival time in premenopausal breast-cancer patients [1]. Several researchers analysed their data, but in general they could not confirm this observation. Nevertheless, two other reports in that series found some influence of the time of surgery during menstrual cycle on prognosis, although, they suggested different time periods as favourable [8, 9]. Purpose. The purpose of this study was to investigate the effect of timing of surgery in a study population which was much larger than the previous studies. Method. All premenopausal patients with primary breast cancer who had been operated at one clinic between 1st of January 1980 and 31st of December 1990 were considered eligible for the study. Based on the day of surgery during the menstrual cycle all patients were grouped according to three proposed categories and to an additional one which consisted of the favourable days from the three proposed categories. We investigated the effects of several prognostic factors and of the timing of surgery on three endpoints: recurrence free survival, distant disease free survival, and overall survival. Results. The traditional prognostic factors had effects in agreement with the literature. Of the different categories for timing of surgery none had a significant influence; the strongest in univariate analysis had a p-value of 0.10 and the trend was in the opposite direction to the one proposed in the literature. These results did not change in multivariate analysis with the Cox model. Conclusions. Timing of surgery does not have an important effect on the prognosis of breast cancer patients. Incorporating other results from the literature, we conclude that it has at most a weak effect. Implications. At present there is no need to incorporate the day of menstrual cycle in the planning of surgery for premenopausal breast cancer patients.
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  • 41
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 35 (1995), S. 39-42 
    ISSN: 1573-7217
    Keywords: psychosocial care ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have established a psychosocial support system that is highly integrated with physician activities and that is tailored to the special needs of our patient population. The core of this system is the close interaction between the physician and the patient counselor, who is a clinical social worker and psychotherapist. Viewed as a permanent member of the breast cancer team, the patient counselor provides psychosocial care in the oncology clinic using normal clinic events as vehicles for interaction. Thus, time spent waiting in the clinic and follow-up phone calls can be converted to sessions for psychological counselling. This approach has been effective in our patient population, where social biases and financial constraints limit the use of out-of-clinic psychiatric services.
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  • 42
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 35 (1995), S. 105-114 
    ISSN: 1573-7217
    Keywords: breast cancer ; focal adhesion kinase ; HER-2 ; novel genes ; protein kinases ; tyrosine kinases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The family of protein kinases includes many oncogenes and growth factor receptors, many of which have been linked to the pathogenesis and progression of cancer. Protein tyrosine kinases such as HER-2/c-erbB-2 and the epidermal growth factor receptor (EGFR) have been linked specifically to breast cancer, and perturbations of HER-2 affect response to chemotherapy. We have reviewed the biology of protein kinases in human breast cancer, as well as their translational applications to breast cancer patients. We have studied the spectrum of protein kinases expressed in human breast cancer cells and have identified four protein kinases with potentially important functions in breast cancer:rak (src-related), TK5 (which we now designate JAK3), the focal adhesion kinase (FAK), and STK1 (human M015/CAK). We describe the potential significance of these genes in breast cancer, as well as our methodology for identifying and characterizing novel genes in breast cancer.
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  • 43
    ISSN: 1573-7217
    Keywords: breast cancer ; aromatase ; estradiol ; hormonal therapy ; CGS 20267
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17β-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue. To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hrurine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples. These data suggest that CGS 20267 can be expected to bring improved response rates in the treatment of metastatic hormone-dependent breast cancer without substantial side effects.
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  • 44
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    Breast cancer research and treatment 33 (1995), S. 39-46 
    ISSN: 1573-7217
    Keywords: breast cancer ; phase II trials ; Taxotere® (docetaxel) ; taxoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Therapy for advanced breast cancer has not improved significantly in recent years, remaining strictly palliative in nature and intent. One approach to increase the effectiveness of the treatment is the introduction of active new drugs. Taxotere® (docetaxel) is a taxoid derivative isolated from the needles of the European yew,Taxus baccata. Taxotere promotes the assembly of microtubules and inhibits their depolymerization. One EORTC Clinical Screening Group (CSG) phase II trial using Taxotere at 100 mg/m2, 1 hour infusion without routine premedication for hypersensitivity reactions, in first line chemotherapy, indicates a high anti-tumor activity: 5 complete and 18 partial responses in 32 patients assessable for response (overall response rate 72%, 95% CI 53%–86%). Other studies confirm this activity in first line and second line chemotherapy for advanced disease and in patients who are refractory to anthracycline containing regimens. Grades III and IV neutropenia without major infection, and grades I and II skin toxicity, were frequently observed adverse events. A fluid retention syndrome (chronic cumulative and non life-threatening toxicity) has been noted in patients treated with Taxotere. Methods for controlling fluid retention — dose reduction to 75 mg/m2 (which has little effect) or routine premedication from the start of treatment — are currently being studied.
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  • 45
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    Breast cancer research and treatment 33 (1995), S. 55-61 
    ISSN: 1573-7217
    Keywords: breast cancer ; menarche ; nulliparity ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Early age at menarche is a known risk factor for breast cancer, some inconsistency in the literature not withstanding. Relative risks for an early menarcheal onset as compared to a late onset vary from 1.0 to 1.9. To avoid (residual) confounding by parity-related factors a case-control study was conducted among nulliparous women. 135 cases and 540 controls were selected from two population-based screening projects for breast cancer in The Netherlands. Four controls were matched to each case for year of birth, for screening-centre, and for number of screening examinations. Women with a menarcheal age of 10 or 11 years showed a 2.2 times (95% confidence interval: 1.2-4.0) higher risk for breast cancer compared to women who had their first menstrual period at 12 years of age or older.
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  • 46
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D isoforms ; Hs578Bst cells ; MCF7 cells ; MDA-MB-231 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cathepsin D from normal (Hs578Bst) and malignant (MCF7, MDA-MB-231) breast cell lines has been characterized with regard to its kinetic properties, activity levels, precursor and processed Mr forms, and isoform composition. Normal cell cathepsin D appears to have a more neutral pH optimum (pH 3.5) than the cancer cell line (pH 3.0–3.2) and greater activity between pH values of 4.0 to 4.5. The two cancer cell lines have approximately 1.5 to 2.0-fold increased total acid protease activity and 2 to 3-fold increased pepstatin-inhibitable protease activity (i.e. cathepsin D) when compared to the normal breast cell line. Western blotting indicates that a major processed form of cathepsin D for all three cell lines occurs at 31 kDa. The cancer cell lines contain significant amounts of cathepsin D precursors of 47 and 42 kDa whereas the normal cell line contains little if any of these precursors. Isoelectric focusing indicates that the normal cell line contains approximately 50% of its total acid protease activity at pIs above 4 whereas the cancer cell lines contain 70–80% of their protease activity at such pIs. In addition, the cancer cell lines contain two to three major isoforms between pIs of 5.5 and 6.3 which were not present in the normal cell line. The isoforms from pI values of 5.5 to 7.3 for all three cell lines are 100% pepstatin-inhibitable. In addition, Western blot analysis indicates that these isoforms contain the processed 31 kDa form of cathepsin D. The combined results indicate that the two breast cancer cell lines are similar to biopsied malignant breast tissue in exhibiting altered acid protease isoform profiles with increased relative amounts of pepstatin-inhibitable and immunoreactive acid protease activity (cathepsin D) compared to normal breast tissue or cells.
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  • 47
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    Breast cancer research and treatment 35 (1995), S. 249-253 
    ISSN: 1573-7217
    Keywords: aromatase inhibition ; aminoglutethimide ; breast cancer ; 4-hydroxy androstenedione ; endocrine therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One hundred and twelve post menopausal or post oophorectomy women with advanced breast cancer (BC) who had all previously had aminoglutethimide (AG) were treated with the potent aromatase inhibitor 4-hydroxy androstenedione (4-OHA). Twenty three women (21%) had a partial response to 4-OHA while another twenty five patients (22%) had stabilization of previously progressing disease. Patients responded to 4-OHA both after previously responding to then relapsing on, and after failing to respond to aminoglutethimide. Toxicity was minimal. This study shows that potent aromatase inhibition with 4-OHA is effective in women with advanced BC who have already been treated with a less potent aromatase inhibitor, and suggests that relative changes in oestrogen levels may be more important than absolute levels.
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  • 48
    ISSN: 1573-7217
    Keywords: breast cancer ; amphiregulin ; heregulin ; cripto-1 ; EGF receptor family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA transcripts was assessed in 60 human primary breast carcinoma. AR and HRG transcripts were expressed respectively in 58% and 25% of the carcinomas as measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas using Reverse Transcriptase-PCR analysis. Coexpression of two or three of these peptides was observed in several specimens. There was no significant association between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2 protooncogene expression in these tumors. However, a significant association between AR expression and estrogen receptor positivity was observed.
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  • 49
    ISSN: 1573-7217
    Keywords: breast cancer ; flow cytometry ; progesterone receptor ; prognosis ; proliferation ; treatment prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although the beneficial effect on breast cancer of adjuvant tamoxifen (TAM) is well established, in the series studied by our group this effect seems to have been restricted to patients with steroid receptor (especially progesterone receptor (PgR)) positive tumors. However, as some patients with PgR-positive tumors manifested recurrence despite adjuvant TAM treatment, the question arose whether some other biological factor(s) could be used to identify these non-responding cases. The level of the S-phase fraction (SPF), as measured by flow cytometry, has been shown to be a useful prognostic marker, prognosis being better in cases where the SPF is low than in those where it is high. The aim of the present study was to relate the prognosis after adjuvant TAM to SPF among patients with PgR-positive tumors. In the PgR-positive group as a whole, the effect of TAM on prognosis was more pronounced in the high SPF group than in the low SPF group (p = 0.005) the respective decrease in 3 year recurrence rate was from 19 to 43% and from 17 to 9%. Multivariate analysis of the data for the TAM-treated group showed the level of PgR concentration (low positivevs. high positive), lymph node status, and tumor size to be independent predictive factors, but not the level of SPF (i.e. highvs. low). By contrast, among patients not treated with TAM, the SPF was a strong independent prognostic factor. To sum up, SPF was a strong independent predictor of outcome only for patients receiving no systemic adjuvant therapy, but not in patients receiving adjuvant TAM. Patients with PgR-positive and high S-phase tumors derived more benefit from TAM than patients with PgR-positive and low SPF tumors.
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  • 50
    ISSN: 1573-7217
    Keywords: adjuvant tamoxifen ; breast cancer ; estrogen receptor positive ; node positive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 370 patients with operable, axillary node positive breast cancer, were randomized to receive tamoxifen (TAM) 20 mg/day for 2 years or no adjuvant hormone therapy. All patients had estrogen receptor (ER) positive (ER 〉 10 pmol/g) primary tumours. 350 patients, 93 younger than 50 years of age and 257 patients 50 years or older, were evaluable for the study. After a median follow up of 76 months, significantly (p = 0.0001) fewer loco-regional, but not distant (systemic), relapses have been recorded in the TAM group. Overall survival was also improved, but even though the study was designed to give maximum benefit from TAM statistically significant effect of TAM seemed to be limited to patients 50 years of age and older.
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  • 51
    ISSN: 1573-7217
    Keywords: breast cancer ; p-glycoprotein ; estrogen receptor ; Ki67 ; dmg resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to further define the clinical utility of p-glycoprotein immunostaining in breast cancer, we examined 101 specimens from patients with advanced breast cancer. There was a significant correlation between estrogen receptor status and p-glycoprotein expression but only for low levels of p-glycoprotein. Premenopausal status appeared to correlate with increased p-glycoprotein expression, but this probably reflects patient selection as premenopausal patients had higher prior exposure to anthracyclines and were more likely to have received chemotherapy as initial treatment. P-glycoprotein expression was highly significantly correlated with expression of the proliferation related antigen Ki67, suggesting that p-glycoprotein expression may well be cell cycle dependent, with overexpression occurring in rapidly cycling cells. These findings may explain reported findings of modulation of p-glycoprotein expression by agents such as anti-oestrogens. P-glycoprotein positive staining did not, however, predict chemotherapy treatment failure or survival duration.
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  • 52
    ISSN: 1573-7217
    Keywords: accessory breast tissue ; axillary mass ; breast cancer ; mastopathy ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in the left breast occurring concurrently with mastopathy of the accessory breast tissue in the bilateral axillary regions, which appeared to be metastatic lymphadenopathy. A preoperative examination, including a mammogram, US, and CT, did not provide us with a definite diagnosis of the axillary masses: it was essential to diagnose the masses preoperatively since a bilateral mastectomy with nodal dissection is called for if the right axillary masses are metastatic from a cancer in the right breast. An intraoperative cytological examination from the bilateral axillary masses revealed adenosis with fibrocystic changes in the accessory breast tissue. We therefore performed a modified radical mastectomy only on the left side. The patient was thus saved from an unnecessary mastectomy of the right breast. Based on our experience, we wish to emphasize that the accessory breast tissue should be considered for a differential diagnosis when evaluating the axillary masses in order to avoid over-surgery, especially when a patient has been diagnosed to have massive breast cancer. An intraoperative cytological examination is strongly recommended to reach a final diagnosis in such confusing cases.
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  • 53
    ISSN: 1573-7217
    Keywords: breast cancer ; mammography screening ; nonattendance ; overall survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The first objective of this study was to analyze the survival rate in a group of 69 breast cancers detected among nonattenders in a randomized mammographic screening trial in relation to 142 clinically detected cancers in a nonscreened control population. By analyzing the cancers of the nonattenders we identified two subgroups, one (A) had actively avoided mammography, had cancers in more advanced stages on diagnosis, and had significantly higher mortality from breast cancer than the control group (p = 0.003). The second subgroup (B) had mammography done outside the screening program. This subgroup had a nonsignificant, slightly better survival (p = 0.19) compared to the control group. Concerning stage the cancers in group B were similar to the cancers by the screening program. The second objective was to analyze women's reasons for nonattendance in the screening program. We interviewed 200 randomly selected nonattenders; 33% stated that they never could imagine having mammography (definite nonattenders), 29.5% that they for various reasons had missed the mammography but could imagine having it next time (possible future attenders), and 32% had been examined outside the program. Reasons for nonattendance included disinterest, medical problems, and fear of X-rays. From this interview investigation we believe that the subgroup of definite nonattenders (33%) is difficult to influence. The second subgroup classified as possible future attenders (29.5%) we believe can be influenced by more information and a new opportunity to receive mammography, i.e., a reminder letter. The third subgroup, those examined outside the screening program (32%) were aware of the benefit of mammography, taking action on their own. Concerning these women's health this seems acceptable; screening outside the program seemed equivalent to that inside the program concerning stage and mortality in breast cancer as shown in the first part of the study.
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  • 54
    ISSN: 1573-7217
    Keywords: anti-estrogens ; toremifene ; hormonal therapy ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In pre-clinical and limited clinical studies, high doses (≥ 200 mg/day) of the triphenylethylene derivative toremifene showed activity in estrogen receptor (ER) negative and ER-unknown metastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone receptor-negative, metastatic breast cancer with limited prior chemotherapy exposure, good performance status, and measurable disease. Twenty eligible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%, weight loss by 20%, and hot flashes by 15%. There was no grade 3–4 toxicity. No objective responses were observed, and 5 of 6 patients with stable disease at 8 weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) is well-tolerated but imparts no detectable activity in hormone receptor-negative, metastatic breast cancer.
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  • 55
    ISSN: 1573-7217
    Keywords: breast cancer ; heat-shock ; prognostic factors ; stress-related protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunostaining for heat-shock protein-27 (HSP-27) was performed on formalin fixed-paraffin embedded sections of 890 node-positive breast carcinomas resected between 1980 and 1986. The follow-up ranged from 2.5 to 10.5 years. A polyclonal antibody (Hu27, dilution: 1/200) was used. A positive cytoplasmic staining was obtained in 383 cases (43%). No difference in distant metastasis-free survival (DMFS) or overall survival (OS) was noted between cases with positive or negative immunostaining. This study suggests that HSP-27 expression is not predictive of the outcome in node-positive breast cancer.
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  • 56
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    Breast cancer research and treatment 36 (1995), S. 103-107 
    ISSN: 1573-7217
    Keywords: angiogenesis ; breast cancer ; prognosis ; therapeutic targets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Angiogenesis, the process leading to the formation of new blood vessels, plays a central role in tumor progression of solid neoplasia. The switch from the avascular to the vascular phase is generally accompanied by rapid primary tumor growth and local invasiveness. Furthermore, angiogenesis is also necessary both at the beginning and at the end of the development of distant metastasis and is implicated in the phenomenon of dormant micrometastases. The angiogenic activity of both the primary tumor and its metastases is the result of the net balance between angiogenic peptides and natural inhibitors, and it is regulated by multiple biochemical and genetic mechanisms. In normal tissues of the adult, unlike invasive cancers, the angiogenic inhibitory pathway predominates. Several experimental and clinico-pathologic studies have confirmed that angiogenesis is specifically involved in transformation and progression of human breast cancer. In particular, clinicopathologic studies have found that the degree of vascularization of primary invasive human breast cancer is heterogeneous and correlates with the prognosis of patients. A number of antiangiogenic agents have been recently discovered, and some are under early clinical evaluation. Thus, angiogenic activity of the tumors represents a potentially novel anticancer therapeutic target. This issue ofBreast Cancer Research and Treatment reports on the most relevant basic biological aspects of angiogenesis, on its clinical role in breast cancer prognosis, and on the implications of inhibition of angiogenesis for future novel anticancer therapeutic approaches.
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  • 57
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    Breast cancer research and treatment 33 (1995), S. 63-73 
    ISSN: 1573-7217
    Keywords: cyclical mastopathy ; breast cancer ; risk ; premenopausal ; case-control study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclical mastopathy (CM) is a common clinical syndrome of premenstrual breast swelling and tenderness. Its symptoms are relieved by reduction in dietary fat intake and, because fat intake may be associated with breast cancer risk, it was hypothesized that CM may also be related to breast cancer risk. This case-control study included 192 premenopausal women with a recent history of axillary node-negative breast cancer and 192 age-matched premenopausal controls. Subjects provided information on diet and risk factors, and they recorded breast symptoms prospectively during one menstrual cycle. Symptoms in the non-cancerous breast of cases and the matched (right or left) breast of controls were examined. A cyclical pattern of symptoms was identified in both groups; breast tenderness scores were similar post-menstrually (p = 0.31) but were significantly higher premenstrually in the case group (p = 0.03). Cases also had a greater premenstrual increase in breast tenderness than controls (p = 0.03). When the effects of other risk factors for breast cancer were included in multivariate analyses, the association of cyclical tenderness with breast cancer persisted (p = 0.05), the odds ratio for severe tenderness being 3.32. Thus, we have identified an association of cyclical breast tenderness with breast cancer risk in premenopausal women. The association persists after consideration of diet and the effects of other breast cancer risk factors.
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  • 58
    ISSN: 1573-7217
    Keywords: breast cancer ; CA15-3 ; CEA ; BCA225 ; serological evaluation ; serum markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum CA15-3, CEA, and BCA225 concentrations were determined in 98 patients with advanced or recurrent breast cancer in an attempt to correlate elevation with clinical status. The rate of serum positivity was 68.4% (67/98), 55.1% (54/98), and 43.9% (43/98) for CA15-3, CEA, and BCA225, respectively. After a 4 weeksinterval, a 20% change of tumor marker concentration from the preceding assay correlated significantly with clinical findings. Significant elevation was predictive of new recurrence or tumor regrowth after complete remission, especially in patients with bone metastasis. The 20% change in concentration at 4 weeks was also useful in patients with tumor marker concentrations persistently beneath the cut-off level for positive. Serological evaluation of tumor markers in patients with advanced or recurrent breast cancer should seek to document 20% changes over a 4 week interval.
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  • 59
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    Breast cancer research and treatment 33 (1995), S. 125-135 
    ISSN: 1573-7217
    Keywords: breast cancer ; chromosome 11q13 ; cyclin D1 ; gene amplification ; oncogene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One in six primary human breast cancers has DNA amplification centered on the cyclin D1 gene (CCND1) on chromosome 11q13. This genetic abnormality is preferentially associated with estrogen-receptor positive tumors and may define a sub-class of patients with an adverse prognosis. AlthoughCCND1 has the credentials of a cellular oncogene, being a target for chromosomal translocation and retroviral integration, the 11q13 amplicon encompasses several other markers andCCND1 is not the only candidate for the key gene on the amplified DNA. To assess their relative importance, we have constructed a physical map of the amplified DNA and compared the extent and frequency of amplification across the region. Since it is likely that the gene providing the selective force for amplification will be expressed at elevated levels, we have also examined expression of both RNA and protein. By these criteria, cyclin D1 remains the strongest candidate for the key oncogene on the amplicon and we are currently investigating the functional consequences of its over-expression.
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  • 60
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; nuclear appearance ; stromal invasion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serial sections on biopsies of 26 women with invasive breast carcinoma were stained for low molecular weight keratins (LKER), high molecular weight keratins (HKER), epithelial membrane antigen (EMA), vimentin (VIM), carcinoembryonic antigen (mCEA and pCEA), and nuclear estrogen (mER) and progesterone receptors (mPGR), using monoclonal and polyclonal sera. Specified areas were identified on serially sectioned slides and staining reactions were compared among areas as well as among patients. The study concludes: (1) LKER staining was positively related to (a) the percentage of tumor cells with densely stained nuclei, (b) a trabecular mode of stromal invasion, and (c) HKER and EMA staining, and inversely related to (d) VIM staining and gross tumor size. (2) HKER was also inversely related to gross tumor size. (3) VIM staining was positively related to pCEA staining. (4) VIM staining was inversely related to staining ER and PGR. (5) LKER, HKER, and EMA staining was stronger in areas of trabecular rather than confluent areas of stromal invasion within the same biopsy. (6) Staining for ER and PGR was not related to mode of stromal invasion, but showed a strong inverse relationship with mitotic index. Positive staining for LKER may be an indicator of better differentiation together with densely staining nuclei and trabecular mode of stromal invasion, whilst VIM and pCEA appear to be related to features indicative of lack of differentiation. Hormone receptor positivity seems to be strongly related to mitotic activity rather than differentiation.
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  • 61
    ISSN: 1573-7217
    Keywords: protein tyrosine phosphatase ; phosphotyrosine ; breast cancer ; histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cellular phosphotyrosine levels are regulated by the balance between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). It is supposed that this balance is disturbed in tumour cells, making the increased or altered activity of PTKs and PTPs likely hallmarks of tumour tissues. Indeed it could be shown that the PTK activity was increased in breast cancer in correlation with prognosis (Hennipmanet al., Cancer Res. 49, 516–522, 1989). In the present report we measured the PTP activities in breast cancer and normal breast tissues. An increase of approximately three- to four-fold was measured in the cytosolic tumour fractions compared to normal, whereas the solubilized membrane fraction PTP activity showed an increase in tumours of approximately 1.5-fold. Remarkably, the membrane PTP activity correlated with the presence of tumour positive axillary lymph nodes (p = 0.004), whereas the cytosolic PTP activity correlated with the mitotic index, a higher PTP activity occurring when the mitotic index was higher than 10 (p = 0.0004). These results indicate that membrane PTP activity may be considered as an index of metastatic potential, whereas cytosolic PTP activity may be a measure of the growth capacity of the tumour. The increase of PTP activity in breast cancers was confirmed by enzyme-histochemical studies. In frozen sections of tumours a strong to moderate activity was found in both tumour cells and interstitial cells. In the interstitium membrane activity was most pronounced, whereas in the tumour cells diffuse staining of the cytoplasm together with a clear membrane staining was demonstrated. Immunoblotting with anti-phosphotyrosine antibodies also reveals differences between the tumours and normal tissues, confirming the disturbance of the balance between protein tyrosyl phosphorylation and dephosphorylation in the tumour cells.
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  • 62
    ISSN: 1573-7217
    Keywords: breast cancer ; BCT ; cosmesis ; local control ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle (LDM), and axillary dissection followed by radiotherapy. In this study, a wide excision of breast tissue was performed to obtain tumor-free margins. The subsequent breast deformity was not corrected in six patients in the early phase of the study (Group 1), and in 16 patients in the late phase (Group 2) in which the breast deformity was not remarkable at the time of operation. Breast deformity was corrected by transposing adipose tissue with LDM on a vascular pedicle in the remaining 51 patients (Group 3). Five year survival was 100%. Two patients developed distant metastases. None were found to have local recurrence. Fifty percent of the Group 1 patients, 69% of the Group 2 patients, and 67% of the Group 3 patients had an excellent or good cosmetic result. However, when the cosmetic results were evaluated in patients who underwent transposition and had small breasts, the results were excellent or good in 76%, compared to 38% in the patients who had reconstructions who had large breasts. The difference was statistically significant (p = 0.0309). Therefore, it was confirmed that wide excision and axillary dissection followed by breast radiation could provide adequate local control, but frequently resulted in breast deformity. However, transposition of adipose tissue may be useful to correct the breast deformity, especially in women with small breasts.
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  • 63
    ISSN: 1573-7217
    Keywords: breast cancer ; laminin ; laminin receptor ; metastasis ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Laminin is a basement membrane glycoprotein whose expression has been widely related to cancer progression. Laminin production by primary breast carcinomas was investigated using immunohistochemistry on archival specimens from a retrospective series with long term follow-up. Laminin production was found to be independent of the clinical and pathological variables analyzed, whereas a statistically significant direct association with the expression of the laminin receptor and a negative association with the differentiation-related antigen Ca-MBr8 were observed. Survival analysis indicated that laminin positivity by itself has no prognostic significance. However, when analyzed together with the laminin receptor expression, laminin was associated with a good prognosis in receptor-negative tumors and with the worst prognosis in receptor-positive tumors.
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  • 64
    ISSN: 1573-7217
    Keywords: angiogenesis ; microvessel density ; vascular endothelial growth factor ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The importance of tumor angiogenesis in the process of tumor growth and progression in solid tumors has been widely accepted. We have investigated the significance of tumor angiogenesis as a prognostic indicator in a retrospective study including 328 primary breast cancer patients. The postoperative survey demonstrated that the microvessel density (MVD) evaluated by immunocytochemical staining for factor VIII-related antigen is a potent prognostic indicator. The relapse-free survival (RFS) rate of patients with over 100 microvessels/mm2 in a microscopic field was significantly worse compared to that of patients with less than 100 microvessels/mm2 (p〈0.00001). The significance of MVD was found in both node-negative and node-positve patients (p〈 0.005 and p〈0.01, respectively). Multivariate analysis confirmed that MVD is an independent prognostic indicator for RFS. In the background factor analysis, MVD was significantly correlated with the number of metastatic nodes (p〈0.01). In addition, the immunocytochemical analysis for vascular endothelial growth factor (VEGF) demonstrated a close association between the increase in MVD and the expression of VEGF (p〈0.001). VEGF status also was a significant prognostic indicator in univariate analysis for RFS (p〈0.01). It was concluded that MVD is a potent prognostic indicator in primary breast cancer. Furthermore, it was also suggested that VEGF plays crucial roles in the promotion of angiogenesis in breast cancer.
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  • 65
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    Breast cancer research and treatment 36 (1995), S. 315-317 
    ISSN: 1573-7217
    Keywords: breast cancer ; paraffin embedded tumor blocks ; triplets ; zygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study is the first to examine the genetic risk in a breast cancer-prone family wherein two of three triplet sisters and their mother manifested breast cancer. The unaffected triplet, the proband, was found to be monozygotic with her deceased sister through DNA testing of tumor blocks and dizygotic to her living affected sister. Genetic counseling implications are discussed.
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  • 66
    ISSN: 1573-7217
    Keywords: CEA ; CA 15.3 ; tumor-associated antigens ; breast cancer ; tumor markers ; early diagnosis of relapse ; metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence, serial serum determinations of both antigens were performed in 1023 patients (follow-up: 1–10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in 533 cases) and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). 246 patients developed metastases during follow-up. Results: CEA and CA 15.3 were elevated (〉 10 ng/ml or 〉 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41% (37/91) of the patients with recurrence, with a lead time of 4.9 ± 2.2 and 4.2 ± 2.3 months, respectively. When patients with locoregional recurrences were excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those that were negative for these receptors in the primary tumor (p 〈 0.001). Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are useful tools for early diagnosis of metastases, mainly in those patients with ER+ or PR+ tumors.
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  • 67
    ISSN: 1573-7217
    Keywords: breast cancer ; nuclear morphometry ; prognosis ; reproducibility ; sample size ; sampling methods
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study compares the influence of two different nuclear sampling methods on the prognostic value of assessments of mean and standard deviation of nuclear area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long term follow up. The first sampling method used was ‘at convenience’ sampling (ACS); the second, systematic random sampling (SRS). Both sampling methods were tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether, besides the sampling methods, sample size had impact on prognostic value as well, the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA values were systematically lower for ACS, obviously due to (unconsciously) not including small and large nuclei. Testing prognostic value of a series of cut off points, MNA and SDNA values assessed by the SRS method were prognostically significantly stronger than the values obtained by the ACS method. This was confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from SRS-50 and SRS-100 measurements were not significantly different. However, for the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In conclusion, compared with the ‘at convenience’ nuclear sampling method, systematic random sampling of nuclei is not only superior with respect to reproducibility of results, but also provides a better prognostic value in patients with invasive breast cancer.
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  • 68
    ISSN: 1573-7217
    Keywords: breast cancer ; ELISA ; invasion ; plasminogen activator ; urokinase receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Urokinase plasminogen activator (uPA) is a proteolytic enzyme involved in degradation of the extracellular matrix during cancer invasion. The levels of uPA and its inhibitor PAI-1 in tumor extracts have previously been demonstrated to be of prognostic value in breast cancer as well as other types of cancer. We have previously characterized a specific cell surface receptor for uPA (uPAR) which strongly enhances the catalytic activity of uPA and is expressed during mammary cancer invasion. In order to quantitate uPAR in breast cancer tissue, we have now developed a sensitive enzyme-linked immunosorbent assay (ELISA), with polyclonal catching antibodies and three monoclonal detecting antibodies. The detection limit of the assay is approximately 0.16 fmol of uPAR in a volume of 100 µl (1.6 pM). There is a linear relationship between signal and uPAR concentration up to at least 6.6 fmol per 100 µl (66 pM). Both free uPAR and uPAR in complex with uPA is detected. The recovery of an internal uPAR standard in breast cancer tissue extracts is above 87%. The intra-assay and inter-assay variation coefficients are 7% and 13%. In order to find a suitable buffer for extraction of various components of the uPA-system from breast cancer tissue, we tested buffers which previously have been used for optimal extraction of estrogen receptor (A), uPA (B), and uPAR (C). Buffer A and B extracted approximately 30% and 50%, respectively, of the amount of uPAR extracted with buffer C. Extracts of samples of breast cancer tissue from 94 patients all contained uPAR in amounts above the detection limit of the present assay, which appears suitable for studies of the potential prognostic value of uPAR in this disease. Significant correlations were found between uPAR, uPA and PAI-1 tumor levels.
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  • 69
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    Breast cancer research and treatment 33 (1995), S. 257-264 
    ISSN: 1573-7217
    Keywords: melatonin ; norethindrone ; breast cancer ; breast cancer prevention ; oral contraceptives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The use of the conventional combination oral contraceptives (containing ethinyl-estradiol and a progestin) is associated with reduced risk of ovarian and endometrial cancer. However, prolonged use of these pills before first term pregnancy apparently increases the risk of pre menopausal breast cancer. We propose that the pineal gland hormone melatonin, combined with a progestin, as a new and novel oral contraceptive combination might prevent breast cancer in long term users. This hypothesis is based on the assumption that women have a propensity to develop breast cancer which correlates with number of ovulatory cycles over their lifetime. In evolution, the phylogenetic point at which women became sensitive to breast cancer evolved at a transfer point of the mechanism of ovulation from seasonal ovulation, which is still common in many mammalian species, to the current human pattern of continuous ovulatory cycles. We suggest that melatonin/ovariansteroid contraceptive will restore the lost mechanism of endogenous anovulation, and thus, by preventing continuous epithelial breast cell proliferation, will reduce the risk of breast cancer in long-term users.
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  • 70
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    Breast cancer research and treatment 34 (1995), S. 195-198 
    ISSN: 1573-7217
    Keywords: Afro-Americans ; breast cancer ; ethnicity ; socioeconomic status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the Department of Defense health care system, all women have the same ability to access health care. Thus, there should be no racial differences in stage at diagnosis solely based on ability to seek health care. A retrospective review of breast cancer cases from 1976–1992 was conducted to determine if there were any differences in stage at diagnosis between Caucasian and Afro-American females. Data was available for 6414 Caucasian and 746 Afro-American females. Stage at diagnosis was similar for both groups. However, Afro-Americans had fewer tumors ≤ 1.0 cm than Caucasians. Afro-American females were younger (median age 50 years versus 58 years in Caucasians). Twenty-four per cent of Afro-Americans were 〈 40 years old compared to only 9% Caucasians. When access to care is not an issue, there are no racial differences in stage of breast cancer at diagnosis.
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  • 71
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    Breast cancer research and treatment 34 (1995), S. 161-169 
    ISSN: 1573-7217
    Keywords: breast cancer ; serum lipids ; apolipoproteins ; fatty acids ; cancer recurrence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Human mammary tissue metabolizes lipids from plasma, a process affected by female gonadal hormones. Both benign and malignant proliferation of breast tissue in women have been associated with changes in plasma lipid and lipoprotein levels.Methods: One hundred consecutive women with breast masses (50 malignant, 50 benign) had diagnostic biopsies followed by axillary node dissection in those with cancer. Fasting serum samples were taken just prior to biopsy and analyzed for lipid fatty acid and lipoprotein levels. Malignant breast tissue was analyzed for hormone receptor binding.Results: Low-density lipoprotein (LDL) components (total cholesterol, LDL-cholesterol, apolipoprotein B) were increased, but not significantly, in cancer patients compared to those with benign masses. Decreased levels of LDL-associated components were found in women with cancer recurrence by 3 years. Three apolipoproteins of high-density lipoprotein (apolipoprotein A-I, apolipoprotein A-II, apolipoprotein D) were more affected by the presence of breast masses than the lipids were. Fibrocystic disease, type of hormone binding, and recurrence within 3 years were significantly related to apolipoprotein changes, especially apolipoprotein D levels with hormone receptor binding and the apolipoprotein A-I/apolipoprotein B ratio with breast cancer recurrence.Conclusions: Prior to diagnostic biopsy, serum lipid and apolipoprotein components of low-density lipoproteins were increased in women with fibrocystic disease and early stage cancer but decreased in women with early recurrence. However, apolipoprotein A-I, apolipoprotein A-II, and apolipoprotein D, of the high-density lipoproteins, were more affected than serum lipids. The ratio of apolipoprotein A-I to apolipoprotein B serum levels at time of biopsy was the best predictor of cancer recurrence.
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  • 72
    ISSN: 1573-7217
    Keywords: breast cancer ; mammography screening ; rural and minority women ; social ecological theory ; community intervention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Breast cancer screening programs do not reach all women at the same rate. Screening mammography use varies according to sociodemographic characteristics; mammography utilization is highest among women in their fifties but then decreases with age. In North Carolina, breast cancer is a particular burden for Black and lower-income women. Black women are more likely to be diagnosed with late stage disease, and their rate of breast cancer mortality is higher than it is for White women even though the incidence in White women is greater. Older, Black, and low-income women are less likely to obtain screening by mammography and clinical breast examination. The Black-White gap is even more pronounced among rural women, in part because they are more likely to be poor. The North Carolina Breast Cancer Screening Program (NC-BCSP) was established to increase the rate of regular mammography screening by an absolute 20% in 3 years among older Black women ages 50 and older in five rural counties in the eastern part of the state. In this paper, we describe the genesis of this comprehensive community intervention model, highlighting the behavioral science constructs, health education principles, and theories of behavioral and organizational change that form its conceptual foundation. NC-BCSP's theoretical foundations include the social ecological perspective, the PRECEDE model of health promotion, the Health Belief Model of individual change, and the “stages of change” transtheoretical model. We also review the experiences and lessons learned from two previous outreach initiatives in North Carolina that provided valuable “lessons” in the development of the NC-BCSP intervention model. In the second half of the paper, we describe the actual NC-BCSP interventions, activities, and evaluation tools, citing specific examples of how the underlying theories are implemented. NC-BCSP's goal goes beyond individual behavior change to raise low mammography screening rates among Black women in rural North Carolina. Its ultimate objective is to create linkages across agencies, and between agencies and communities, that will endure after the research project ends.
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  • 73
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    Breast cancer research and treatment 35 (1995), S. 97-104 
    ISSN: 1573-7217
    Keywords: breast cancer ; gene amplification ; genomic instability ; polymorphisms ; ras alleles ; VNTR (variable number tandem repeat)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Over the last several years, evidence has accumulated to support the idea that rare Ha-ras polymorphisms are associated with inherited susceptibility to certain human cancers. A recent epidemiologic study conducted at our institution found a significant association specifically with breast cancer, although the mechanism underlying this relationship remains unclear. We have proposed that rare Ha-ras alleles are markers of a genomic instability that predisposes to breast cancer. To address this hypothesis, we are investigating the relationship between the presence of rare alleles and another form of instability, gene amplification, and are developing new methodologies both to improve VNTR allele length detection and to characterize the internal repeat sequence variations of the various alleles. These studies should enable us to more clearly define the role of this region in cancer development by delineating VNTR structure and function and the mechanisms of rare allele generation. Ultimately, we hope to identify VNTR characteristics that will permit more accurate cancer risk assessment.
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  • 74
    ISSN: 1573-7217
    Keywords: human breast tissue ; breast cancer ; thymidylate synthetase ; nodal metastasis ; mitosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thymidylate synthetase (TS) is a key enzyme as a methyl donor in the methylation reaction from dUMP to dTMP. TS activity was assessed in various tissue of mammary disorders. The descending order of TS activity was as follows: cancer-positive nodes, primary cancers, cancer-negative nodes, benign lesions, and normal parenchyma. Significant differences in TS activity were found between the positive nodes and each of the other tissues (p 〈 0.01). In node-positive cases, a significant correlation in TS activity was found between the primary cancers and positive nodes (r = 0.616, p = 0.033). There was no correlation between the nodal status and the TS activity in primary cancers. In 11 of 12 cases, the TS activity of positive nodes was higher than the ‘calculated’ TS activity of the primary cancer, which was defined as the TS activity per unit weight of cancer cells. A significant correlation was found between the calculated TS activity and the mitotic frequency in primary cancers (r = 0.697, p = 0.0001). On the other hand, a significant correlation could not be found between the TS activity and the mitotic frequency in positive nodes (r = 0.364, p = 0.244).
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  • 75
    ISSN: 1573-7217
    Keywords: breast cancer ; CD44 variants ; metastasis ; tumor progression marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Splice variants of CD44 expressed in a metastasizing cell line derived from a rat pancreatic adenocarcinoma have been shown recently to confer metastatic potential onto non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Homologues of these variants have also been detected in a variety of human malignancies. Using antibodies raised against a bacterially expressed fusion protein containing variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins on tumors of the female breast. The material examined included normal tissue, hyperplastic lesions, 103 primary invasive mammary carcinomas, 10in situ carcinomas, 12 local recurrences and 18 lymph node metastases. Using a polyclonal serum directed against several variant CD44 epitopes, normal mammary epithelia as well as ductal hyperplasias were negative for these splice variants, while the variant CD44 epitopes were detectable in all but six of the primary invasive carcinomas. From the reaction with various monoclonal antibodies and polyclonal sera specific for individual epitopes it is obvious that the tumors predominantly express CD44 variants encoded by exons v5 to v7. Interestingly, all investigated lymph node metastases reacted positively with the variant-specific antibodies, in contrast to primary tumors which reacted in 54% to 86% of the cases, depending on the antibody used. Statistical analysis revealed a significant correlation between expression of variant exons v3/v4 and v6 and increased tumor grade (p = 0.001 and p 〈 0.05, respectively; Fisher's exact test). Exon v6 is carried by the variants which confer metastatic capability in the rat. These results indicate that the expression of the CD44 variants is upregulated in mammary carcinomas and is closely linked to tumor anaplasia.
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  • 76
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    Breast cancer research and treatment 36 (1995), S. 169-180 
    ISSN: 1573-7217
    Keywords: angiogenesis ; breast cancer ; endothelial cell ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Abundant evidence has shown that tumor growth and metastasis are dependent upon tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within the tumor. Until TA occurs, tumors grow no larger than 2–4 mm in diameter. Also, TA is necessary at the beginning and at the end of the metastatic cascade of events. Thus, it seems reasonable that increasing intratumoral microvascular density (iMVD) might correlate with greater tumor aggressiveness, such as a higher frequency of metastases and/or decreased survival. Indeed, in 1991 my colleagues and I reported a statistically significant association between greater incidence of metastases in patients with breast carcinoma and increasing iMVD. Microvessel density was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density (neovascular “hot spot”). This was done after endothelial cells, lining the microvessels, had been highlighted with anti-factor VIII-related antigen/von Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti-CD31, have shown that the association of greater tumor aggressiveness with increasing iMVD exists not only in breast carcinoma, but also in other solid tumors. This article reviews the methods of highlighting intratumoral vessels and describes the techniques for counting these vessels for assessing iMVD.
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  • 77
    ISSN: 1573-7276
    Keywords: breast cancer ; bone metastasis ; type I collagenase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Bone is one of the most common sites of metastasis in breast cancer. For metastasis to occur in bone, tumor cells must induce osteolysis by osteoclasts. Degradation of the osteoid layer by type I collagenase is a necessary process before osteolysis can occur because the psteoid layer hinders osteoclasts from adhering to bone. In this study, we investigated the function of H-31 human breast cancer cells in inducing type I collagenase production and in enhancing bone resorption. H-31 cells did not themselves produce type I collagenase whereas MG-63 human osteoblast-like cells and MC3T3-E1 mouse osteoblast cells constantly produced type I collagenase. When these osteoblast-like cells were cocultured with H-31 cells, type I collagenase production was enhanced. The same enhancement occurred when the conditioned medium of H-31 cells was added to the osteoblast-like cells. The activity of this type I collagenase was inhibited by EDTA and minocyclin, an inhibitor of matrix metalloproteinases, hence it was identified as matrix metalloproteinase-1 (MMP-1). H-31 cells exhibited chemotactic migration towards collagen; therefore, collagen degraded by MMP-1 may play an important role in the localisation of breast cancer cells like H-31 to bone. In an organ culture system using newborn mouse calvaria, the conditioned medium of H-31 cells increased the concentration of calcium in the medium, and this effect was inhibited by minocyclin, indicating that bone resorption occurred in this system. Based on these observations, we speculate that type I collagenase produced by osteoblast cells in response to breast cancer cells (exemplified by H-31) may facilitate degradation of the osteoid layer and the homing of breast cancer cells to bone. This can lead to osteolysis by osteoclasts, a crucial event for bone metastasis.
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  • 78
    ISSN: 1573-7225
    Keywords: Abortion ; breast cancer ; cohort studies ; females ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer. Thus, the association of fatal breast cancer and spontaneous abortion was examined in a large prospective study of United States adult women. After seven years of follow-up, 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories. Results from Cox proportional hazards models, adjusted for other risk factors, showed no association between a history of spontaneous abortion and risk of fatal breast cancer (rate ratio [RR]=0.89, 95 percent confidence interval [CI]=0.78–1.02). The RR did not increase with increasing numbers of abortions. Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion (RR=0.76, CI=0.54–1.05). Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant (RR=0.61, CI=0.27–1.38) or whose only pregnancy ended in a livebirth (RR=0.72, CI=0.32–1.65). These findings do not support an association between spontaneous abortion and fatal breast cancer.
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  • 79
    ISSN: 1573-6849
    Keywords: breast cancer ; chromosome 1 ; FISH ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fluorescencein situ hybridization (FISH) was used to establish the copy number of chromosome 1 in a set of nine breast tumours in which the chromosome had previously been shown to have undergone a variety of rearrangements by loss of heterozygosity studies. In each case, FISH with satellite III DNA from chromosome 1q12 confirmed the results obtained by Southern hybridization. Importantly, in all five cases with rearrangements thought not to involve the centromeric region, FISH showed that the events had not disrupted the gross chromosome structure. This study highlights the potential of using the two techniques together to obtain a clearer picture of both large- and small-scale alterations to chromosomes in solid tumours.
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  • 80
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Females of the marbled salamander, Ambystoma opacum, store sperm in exocrine glands called spermathecae in the roof of the cloaca. Eggs are fertilized by sperm released from the spermathecae during oviposition. Some sperm remain in the spermathecae following oviposition, but these sperm degenerate within a month and none persists more than 6 mo after oviposition. Thus, sperm storage between successive breeding seasons does not occur. Apical secretory vaculoes are abundant during the fall mating season and contain a substance that is alcian blue+ at pH 2.5. Production of secretory vacuoles decreases markedly after oviposition, and the glands are inactive by the summer months. Ambystoma opacum is a terrestrial breeder, and some mating occurs prior to arrival at pond basins where oviposition occurs. Mating prior to arrival at the ovipository site may prolong the breeding season, leading to fitness implications for both males and females. Females have opportunities for more matings, and the possibilities for sperm competition in the spermathecae are enhanced. © 1995 Wiley-Liss, Inc.
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  • 81
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Alcichthys alciocornis has a viscous ovarian fluid in the ovarian cavity, which plays an important role in its unique mode of reproduction called internal gametic association (i.e., internal insemination and sperm-egg association but a delay in the physiological fertilization until spawning). Seasonal changes in fine structure of the inner epithelial lining and capillary endothelium of the ovary revealed that ovarian fluid originated as a result of the secretory activity of the tissues. The ovarian cavity of A. alcicornis is lined with an ovigerous lamella epithelium and an ovarian wall epithelium. During the spawning period, both epithelia actively secreted proteinaceous substances which seemed to constitute the ovarian fluid. The substances appear to be synthesized in the rough-surfaced endoplasmic reticulum from the material which was transported from the blood capillary, taken into the epithelial cells by endocytosis, accumulated in secretory vesicles via Golgi apparatus in the cells, and finally released into the ovarian cavity by exocytosis. Microapocrine secretion was also observed to occur in both epithelia. Secretory activity of both epithelia by exocytosis and microapocrine secretion showed distinct seasonal changes. Active exocytosis and microapocrine secretion were observed during the spawning period (April-May). These activities slightly declined during the degeneration period (May-June) and were lost during the early recovery period (July). During the mid to late recovery period (October-March), there was some exocytosis but no microapocrine secretion. © 1995 Wiley-Liss, Inc.
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  • 82
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    Journal of Morphology 223 (1995), S. 167-174 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cell surface morphology of hamster decidual cells isolated from day 8 implantation swellings was studied, using both phase-contrast and scanning electron microscopy. Two kinds of cells, fibroblastic and epithelioid, were identified in cultures examined by phase-contrast microscopy. Fibroblastic cells were spindle-shaped, having pointed or blunt terminals on one end and bifid or webbed projections at the other end. Epithelioid cells, on the other hand, were flat and discoid, having a distinctively ruffled plasma membrane. Further, the plasma membrane of epithelioid cells formed rope-like or flange-like processes. The significance of such adaptations is discussed. © 1995 Wiley-Liss, Inc.
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  • 83
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    Journal of Morphology 223 (1995), S. 149-166 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study investigates the effect of developmental stage on thyroid hormone (TH)-mediated remodeling in the skeletal tissues of hemidactyliine plethodontid urodeles. Rate of morphogenesis was quantified in 17 metamorphic tissues for three different size-age classes of Eurycea bislineata larvae immersed in a metamorphic dosage of T4. Extent of morphogenesis after a 3-week immersion was also quantified in these tissues plus four larval ones for the full size range of E. bislineata larvae and for less complete size ranges of E. wilderae, E. longicauda guttolineata, Gyrinophilus porphyriticus, and Pseudotriton ruber larvae. Although all tissues respond more slowly with decreasing size/age, two tissue-specific effects are evident in all species. Larval ossifications are less inducible than metamorphic ossifications, and progressive metamorphic events are more retarded and, in some cases, more prone to abnormal morphogenesis than regressive ones. The first effect agrees with the prediction that tissues that naturally remodel at metamorphosis are more responsive to a metamorphic dosage of TH than those that respond at a larval stage and lower TH. The second effect agrees with the prediction that progressive morphogenesis is more likely to be impaired at small size than regressive morphogenesis, although the frequent discrepancies between individuals of similar size implicate developmental age more than size in this effect. Collectively, these two effects provide only equivocal support for the hypothesis that direct development in plethodontids evolved via precocious TH activity. However, the unexpected transition from ceratobranchial replacement to ceratobranchial shortening in medium-sized larvae suggests that the former pathway requires a longer period of cell specification at low TH. Since ancestral plethodontids appear to have been distinguished by an exceptionally long larval period with exceptionally low TH activity, this developmental prerequisite may in turn be partly responsible for their singular evolution of ceratobranchial replacement. © 1995 Wiley-Liss, Inc.
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  • 84
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    Journal of Morphology 223 (1995), S. 203-214 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The sagittal otolith of Hyperoglyphe antarctica (Centrolophidae: Teleostei) has a prismatic structure in which the anti-sulcal growth axes of each prism consist of a series of nested cones each composed of a mineral layer followed by an organic matrix layer. Broken sections show the mineral layers to be composed of stacks of crystals. Otolith matrix that has been decalcified and air-dried, or critical-pont-dried, retains a periodic structure of repeating high and low matrix density. At high magnifications, both broken whole crystal surfaces and decalcified matrix surfaces have a granular structure. Chloroxbleached whole otoliths also show a granular crystalline structure. At higher magnifications, the air-dried matrix showed a parallel fiber structure with similar dimensions to keratin fibers. © 1995 Wiley-Liss, Inc.
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  • 85
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    Journal of Morphology 223 (1995), S. 191-201 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Ultrastructural descriptions of the dipnoan heart are lacking. Many ultrastructural features of the heart of the Australian lungfish, Neoceratodus forsteri, resemble those of other lower vertebrates. The epicardial cells appear to be adapated for the exchange of material with the pericardial fluid. The most prominent features of the endocardial cells are numerous moderately electron-dense vesicles found within the cytoplasm. These organelles might have an endocrine function. The myocardiocytes are typically small. The banding pattern of the sarcomere is shared with most fish. The intercalated disc has a convoluted path and consists of desmosomes and fascia adherens. Caveolae are a prominent feature of the sarcoplasm. The sarcoplasmic reticulum is sparse, and T-tubules are lacking. Atrial myocardial dense bodies occur in vast numbers throughout the atrium and are occasionally seen in the ventricle. These vesicles are chromaffin-positive but fail to show catecholamine fluorescence. They are likely to contain peptides related to ANP. Subendothelial cells exhibiting catecholamine-specific fluorescence are scattered throughout the atrium. Ultrastructurally these cells contain many chromaffin-positive granules. Chromaffin cells represent another cell type with a probable endocrine function within the heart of N. forsteri. © 1995 Wiley-Liss, Inc.
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  • 86
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    Journal of Morphology 223 (1995) 
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    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 87
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    Journal of Morphology 223 (1995), S. 263-268 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A complex of lymphoepithelial organs, the “anal tonsils,” is a consistent structure in the anal canal of the bottlenose dolphin, Tursiops truncatus. This complex occurs as a circumferential cluster of discrete tonsil like aggregations of lymphoid tissues, together with epithelial ducts (“crypts”) and occasional mucus secretory units in the extreme lower portion of the intestinal tract. These structures are concentrated in the segment lined by stratified squamous epithelium and extend for a variable distance cephalad from the anal aperture. The tonsils appear to be most active, judged by the amount of lymphoid tissue present, in young animals. Depletion of lymphocytes and cystic enlargement of the crypts, probably representing functional as well as morphological involution, is a consistent feature of older animals. © 1995 Wiley-Liss, Inc.
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  • 88
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    Journal of Morphology 223 (1995), S. 269-287 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The prenatal development of epidermis, dermis, and hypodermis was studied in embryos of different ago of two delphinid species (Stenella attenuata, Delphinus delphis), using light and transmission electron microscopical methods. The delphinid embryo is covered by a multilayered tissue formed by four different epidermal generations (periderm, stratum intermedium-I, str. intermedium-II, str. spinosum) produced by the str. basale. The first layer appears at about 40-50 mm of body length, the second type (s.i.-I) about 60-160 mm, and the third type (s.i.-II) is present at 160-500 mm. The first spinosal cells are produced at 225-260 mm body length; thenceforth, the epidermis increases continuously in thickness. Epidermal ridge formation begins about 400-mm body length. The development of the dermis is characterized by the early production of thin connective tissue fibers (40- 70-mm body length) and simultaneously the cutaneuous muscle matures in structure. Vascular development intensifies between embryos of 150-225 mm, and collagen production increases markedly in fetuses of 225-260-mm length. These events are paralledled by an increase in dermal thickness. The first elastic fibers can be recognized in the skin from the abdomen at about 600-mm body length. The development of the hypodermis is marked by very rapid and constantly progressing growth, beginning about 60-mm body length. The first typical fat cells appear in animals of 360-400 mm. Regional differences are obvious for all skin layers with regard to the flippers, where structural maturation proceeds more rapidly than in dorsal or abdominal regions. © 1995 Wiley-Liss, Inc.
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  • 89
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    Journal of Morphology 223 (1995), S. 289-302 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Functional comparative morphology of predatory legs in five species of water bugs (Ilyocoris cimicoides, Nepa cinerea, Ranatra linearis, Notonecta glauca, and Gerris lacustris) has been investigatd adn the following peculiarities of leg design were revealed.1Subcoxal articulation may be monoaxial (G. lacustris, N. glauca), or, in contrast to walking leg type, biaxial (N. cinerea, R. linearis, I. cimicoides); the first axis is oriented along the coxa (torsion axis), the second one is perpendicular to the first (non-torsion axis).2In contrast to walking leg type, which is characterized by cross suspension of the axis of coxal rotation in thoracal skeleton, this axis in G. lacustris is placed vertically. Non-torsion coxal axis in R. linearis is oriented strongly transversal. This axis directs the leg strike forward.3Legs in the majority of species are planar: Torsion axes of the coxa, femur, and tibia are placed in the same plane. Axes of rotation of consequent joints in I. cimicoides are reciprocally sloped. Therefore, the end of the leg outlines the spiral trajectory, when all angles of joints are opening (closing). This is an adaptation for clinging to the stems of water plants.4Passive adduction of the femur in the trochanter-femoral joint in N. glauca allows it to go around protuberances of the body wall, when the leg is sliding along them; recurrent femur movement during releasing from the obstacele is active due to the rt.fe muscle.5Only R. linearis has predatory legs, which permit the high-speed pursuit of potential prey; other species realize this function using the swimming legs, whereas the forelegs are used for the manipulation movements.6Muscle arrangement in the prothorax of different species reflects both leg construction and constructional constraints of body design. Powerful flexor muscles (co1, co2, co3, co5, fl.ti, et.ti in R. linearis; fl.ta, fl.ti in N. glauca; fl.ti in I. cimicoides) have long tendons and short muscle bundles, which originate on the leg wall. As a result, the powerful force is developed along the muscle tendon.7Some features of the predatory leg are common for the species studies: elongation of coxae, thickening of femora, and increase of the degree of junction of tibia and tarsus. The muscles, which move the distal segment of the leg, are reinforced and the sclerite of the fl.ti tendon is enlarged. The joint angle of the distal segment is increased to 120°. © 1995 Wiley-Liss, Inc.
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  • 90
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    Journal of Morphology 223 (1995), S. 341-355 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Piranhas, like many teleosts, change their diets on both ontogenetic and phylogenetic time scales. Prior studies have suggested that pervasive morphological changes in body form on a phylogenetic time scale may be related to changes in diet, but previous reports have found little shape change in piranhas on an ontogenetic time scale. We re-examine the post-transformational allometry of body form in one piranha, Pygocentrus nattereri (Kner), using the method of thin-plate splines decomposed by their partial warps. We find substantial evidence of allometry, primarily elongation of the mid-body relative to the more anterior and posterior regions, elongation of the postorbital and nape regions relative to the more anterior head and posterior body, and deepening of the head relative to the body. In addition to these pervasive changes throughout the body, there are some that are more localized, especially elongation of the postorbital region relative to eye diameter and snout, and an even more localized elongation of the snout relative to eye diameter. Initial dietary transitions are associated with changes in head and jaw proportions, but rates of shape change decelerate through growth, so that the final transition to a diet increasingly dominated by small whole fish appears associated with change largely in overall body size. © 1995 Wiley-Liss, Inc.
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  • 91
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 224 (1995), S. 87-96 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Muscles in the body wall, intestinal wall, and contractile hemolymphatic vessels (pseudohearts) of an oligochaete anelid (Eisenia foetida) were studied by electron microscopy. The muscle cells in all locations, except for the outer layer of the pseudohearts, are variants of obliquely striated muscle cells. Cells comprising the circular layer of the body wall possess single, peripherally located myofibrils that occupy most of the cytoplasm and surround other cytoplasmic organelles. The nuclei of the cells lie peripherally to the myofibrils. The sarcomeres consist of thin and thick myofilaments that are arranged in parallel arrays. In one plane of view, the filaments appear to be oriented obliquely to Z bands. Thin myofilaments measure 5-6 nm in diameter. Thick myofilaments are fusiform in shape and their width decreases from their centers (40-45 nm) to their tips (23-25 nm). The thin/thick filament ratio in the A bands is 10. The Z bands consist of Z bars alternating with tubules of the sarcoplasmic reticulum. Subsarcolemmal electron-dense plaques are found frequently. The cells forming the longitudinal layer of the body wall musculature are smaller than the cells in the circular layer and their thick filaments are smaller (31-33 nm centrally and 21-23 nm at the tips). Subsarcolemmal plaques are less numerous. The cells forming the heart wall inner layer, the large hemolymphatic vessels, and the intestinal wall are characterized by their large thick myofilaments (50-52 nm centrally and 27-28 nm at the tips) and abundance of mitochondria. The cells forming the outer muscular layer of the pseudohearts are smooth muscle cells. These cells are richer in thick filaments than vertebrate smooth muscle cells. They differ from obliquely striated muscle cells by possessing irregularly distributed electron-dense bodies for filament anchorage rather than sarcomeres and Z bands and by displaying tubules of smooth endoplasmic reticulum among the bundles of myofilaments. © 1995 Wiley-Liss, Inc.
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  • 92
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In this report, the gonads of 32 glandulocaudine species, representing 18 genera, are compared with 11 outgroup characiform species. Through the presence of spermatozoa within the ovarian cavity, internal fertilization of the female is confirmed for the 16 genera for which mature ovaries were available. No outgroup ovary studied contains spermatozoa. All mature glandulocaudine testes have a large portion of the posterior testis, which is devoid of developing germ cells and spermatocysts (aspermatogenic), devoted to sperm storage, with the degree of partitioning in that region varying greatly within the group. All outgroup species examined have spermatozoa with spherical nuclei. With the exception of the species of the genus Planaltina, which also have spherical nuclei, all glandulocaudines have elongated nuclei, which vary among the species from 3.6 μm to 31.6 μm in length. Distinct sperm packets (spermatozeugmata) are formed in five genera by two different methods. In the genera Xenurobrycon, Tyttocharax, and Scopaeocharax, all of the tribe Xenurobryconini, the spermatozeugmata are formed within the spermatocysts and released fully formed. In all genera of the tribe Glandulocaudini, which includes Glandulocauda and Mimagoniates, loose spermatozoa are released which cluster into spermatozeugmata within the posterior storage areas. These morphological specializations are discussed within a phylogenetic framework as adaptations for internal fertilization and are hypothesized to be independently derived. © 1995 Wiley-Liss, Inc.
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  • 93
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    Journal of Morphology 224 (1995), S. 199-203 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Interdigitating cells in the thymus of the sea bass, Dicentrarchus labrax, occur principally in the internal zone and in the border with the external zone. Ultrastructurally, the most characteristic cytological features of these cells are their low electron density, complicated labyrinthine membrane-membrane contacts, scantiness of cytoplasmic organelles, presence of Birbeck-like granules, juxtanuclear tubulo-vesicular complex, and phagocytic capacity. © 1995 Wiley-Liss, Inc.
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  • 94
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Morphological and ultrastructural features of the salivary glands and proboscises of Placobdella ornata, Placobdella parasitica, and Desserobdella picta were studied by light and electron microscopy. Chemical composition of the salivary cells was investigated using a variety of histochemical techniques. Placobdella ornata and P. parasitica have compact salivary glands with discrete pairs of anterior and posterior glands, while the salivary cells contain one mucous and three proteinaceous secretions. Salivary glands of D. Picta are diffusely arranged and contain two mucous and two proteinaceous secretions. A cobalt-lysine forward-filling technique revealed that individual salivary cells consist of a roughly spherical soma and an elongated ductule. The majority of the internal space in a salivary soma is densely packed with spherical secretory granules which displace the cytoplasm to the periphery of the cell. Bundles of individual ductules enter the base of the proboscis on opposite sides and extend anteriorly. The ductules, also packed with secretory granules, are surrounded by microtubules associated with agranular endoplasmic reticulum, and merge with deep invaginations of the proboscis cuticle. The secretory granules are released at the end of these invaginations or pores. Pores were found on the tip, along the body, and on the luminal wall of the proboscises in all three species. © 1995 Wiley-Liss, Inc.
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  • 95
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 225 (1995), S. 61-75 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Longitudinal and principal strain recordings were made in vivo at three sites (dorsal, anterior, and ventral) on the humeral midshaft of pigeons executing five modes of free flight: Take-off, level flight, landing, vertical ascent, and near-vertical descent. Strains were also recorded while the birds flew carrying weights that were 33%, 50%, or 100% of their body weight. The relative distribution of strain measured at the three surface midshaft sites and across the bone's cortex was found to be similar for all flight modes. Principal strains recorded in the dorsal and ventral humerus indicated considerable torsion produced by aerodynamic loading of the wing surface posterior to the bone. Measured torsional shear strains (maximum: 2,700-4,150 μ ε during level flight) were 1.5 times greater than longitudinal strains. In addition to torsion, the humerus is also subjected to significant dorsoventral bending owing to lift forces acting on the wing during the downstroke. Analysis of the cross-sectional distribution of longitudinal strains at the humeral midshaft cortex shows that the orientation of bending shifts in a regular manner during the downstroke, indicating that the wing generates progressively more thurst (vs. lift) later in the downstroke. This shift is less during take-off and vertical ascent when greater lift is required. Peak principal and longitudinal strains increased by an average of only 50% from landing to vertical ascending flight and take-off (e.g., dorsal humerus: -1,503 to -2,329 μ ε) and did not exceed -2,600 μ epsiv; at any site, even when the birds flew carrying twice their body weight. Strains recorded when birds flew at two times their body weight (100% BW load) were similar in magnitude to those recorded during vertical ascent and take-off and likely represent those developed during maximal performance. Strains developed within the midshaft were maximal in the anterodorsal and posteroventral cortices, not at the dorsal, ventral, and anterior sites at which strain was recorded. Consequently, maximum strains experienced by the bone are probably 20-25% greater than those recorded (ca. 3,200 μ ε), indicating a safety factor of about 3.5 for compressive strain failure. The much higher shear strains, however, indicate a lower safety factor (1.9), in which the bone's torsional strength is its most critical design feature. Finally, the magnitude and distribution of strains developed in the humerus of pigeons are generally similar to those recorded in the humerus of large fruit-eating bats during flight. © 1995 Wiley-Liss, Inc.
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  • 96
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    Journal of Morphology 225 (1995), S. 107-123 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cephalometry was used to detect patterns of cranial growth in fetal bats that were stained differentially for bone and cartilage. Three developmental features distinguish embryos of taxa that echolocate nasally from embryos of taxa that echolocate orally: (1) the basicranium is retained ventral to the cervical axis, (2) the rostrum is retained below the basicranial axis, and (3) the lateral semicircular canals are rotated caudally. Together, the first two actions align the fetal nasal cavity with what will be the long axis of the adult body in flight. The third action aligns the lateral semicircular canals with the horizontal. In contrast, skulls of oral-emitting taxa are constructed such that the oral cavity is aligned with the long axis of the body in flight. The evolution of head posture and skull form in microchiropteran bats has been constrained by the demands of vocalization, i.e., ultrasonic echolocation. Accordingly, the ontogeny of the microchiropteran skull has been canalized along two distinct developmental paths - oral-emitting and nasal-emitting Baupläne. © 1995 Wiley-Liss, Inc.
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  • 97
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 225 (1995) 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
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  • 98
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    Journal of Morphology 225 (1995), S. 251-260 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Assulina muscorum secretes morphologically altered shells when cultured in a medium with 5 mM caffeine. The siliceous scales, normally distributed in a regular overlapping pattern, are disorganized, thicker and wider than normal, and occasionally have incompletely silicified surfaces that appear irregular in profile in transmission electron microscopic ultrathin sections. The shape of the silica deposition vesicles (SDVs) in the cytoplasm is altered and they are less regularly arranged. The swollen appearances of the SDVs, and of nearby Golgi tubules, give additional evidence that caffeine affects the fine structural morphology of membranous secretory organelles and can disrupt their normal depositional activity. In addition to the greater thickness and width of the siliceous scales in caffeine-treated cells, the length and width of the shell are larger compared to controls, but the aspect ratio (length / width) is smaller. The latter is attributed to a larger increase in width relative to the increase in length of the caffeine-reated cells. Since some of the scales are deposited with the long axis laterally on the shell surface, in addition to being greater in width, this raises the interesting question of whether the morphology of the SDVs and the siliceous products influences the size and morphogenesis of the shell. Further research is needed to clarify the interaction of the SDVs with the cytoplasmic cytoskeletal system during shell morphogenesis. © 1995 Wiley-Liss, Inc.
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  • 99
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: This study deals with some macroscopical, microscopical, and ultrastructural aspects of the spinal cord central canal of the German shepherd dog. The caudal end of the spinal cord is constituted by the conus medullaris, which may extend to the first sacral vertebra, the terminal ventricle, and the filum terminale. The latter structure is considered as internum (second to third sacral vertebrae) or externum (fifth caudal vertebra), according to its relation to the dura mater. Occasionally, there is a second anchorage which is close to the level of the sixth caudal vertebra. The central canal is surrounded by a ciliated ependymal epithelium, which differs depending upon the levels. The most caudal part of the filum terminale bears a columnar ciliated ependymal epithelium surrounded by two layers of glia and pia mater, which separate the central canal from the subarachnoid space. Microfil injections show a communication between the cavity and the subarachnoid space, as the plastic is able to pass through the ependymal epithelium. At the level of the terminal ventricle there are real separations of the ependymal epithelium, which seem to connect the lumen of the spinal canal with the subarachnoid space. These structures probably constitute one of the drainage pathways of the cerebrospinal fluid. The diameter of the central canal is related to the age of the animal. However, even in very old animals the spinal cord central canal reaches the tip of the filum terminale and remains patent until death. At the ultrastructural level the ependymal cells present villi, located on cytoplasmic projections, cilia, dense mitochondria, and oval nuclei. © 1995 Wiley-Liss, Inc.
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  • 100
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    New York, NY : Wiley-Blackwell
    Journal of Morphology 224 (1995), S. 179-198 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Female reproductive tracts of the viviparous neo-tropical onychophoran Peripatus acacioi have been examined at different times throughout the year, and the altering relationship between the developing embryo and the uterus is described. Depending on her age and time of year, the female may have one or two generations of embryos within her uterus. The uterine wall consists of a thin outer epithelium and basal lamina, three layers of muscles, and a thick basal lamina beneath an inner epithelium lining the uterus lumen. These layers are consistent along the length of the uterus apart from the inner epithelial lining, which varies according to position in the uterus and the developmental stage of embryos contained in the uterus. Early embryos are positioned along the length of the uterus and therefore have space in which to grow. During cleavage and segment formation, each embryo is contained within a fluid-filled embryo cavity that increases in size as the embryo grows. Morulae and blastulae are separated by lengths of empty uterus in which the epithelial lining appears vacuolated. Until the process of segment formation is complete, the embryos are attached to a placenta by a stalk and remain in the same part of the upper region of the uterus. As these embryos grow, the lengths of vacuolated cell-lined uterus between them decrease. Each embryo cavity is surrounded by the epithelial sac, the maternal uterine epithelium, which becomes overlaid by a thin layer of cells, the embryo sac, which is believed to be of embryonic origin. The placenta is a syncytial modification of the epithelial sac located at the ovarian end of each embryo cavity covered by the embryo sac and is analogous to the mammalian noninvasive epitheliochorial placenta. Segment-forming embryos have their heads directed toward the ovary. As the embryo gets longer during segment formation, its posture changes from coiled to flexed. Once segment formation is complete, the embryo loses contact with its stalk, an embryonic cuticle forms, and the embryo turns around so that its head is directed toward the vagina. The embryo escapes from its embryo sac and moves to the lower part of the uterus. In the lower part of the uterus, the straightened fetuses are first unpigmented but subsequently become pigmented as the secondary papillae on the body surface form and an adult-type cuticle forms beneath the embryonic cuticle. While the embryos are contained within their embryo cavities, nutrients are supplied by the placenta. Throughout development the mouth is open and in the mature fetus the gut is lined by peritrophic membrane and material is present in the gut lumen. Trachea have been observed only in fetuses that were ready for birth. Insemination, cyclical changes in the uterine epithelium, and the nature of the cuticle shed at parturition are discussed. © 1995 Wiley-Liss, Inc.
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