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  • 2000-2004
  • 1995-1999  (146)
  • 1890-1899
  • 1995  (146)
  • breast cancer
  • ddc:000
  • 1
    Electronic Resource
    Electronic Resource
    Timing of surgery in relation to the menstrual cycle and its influence on the survival of Japanese women with operable breast cancer (1995)
    Springer
    Surgery today 25 (1995), S. 519-524 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00311308
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  • 2
    Electronic Resource
    Electronic Resource
    Evaluation of aspiration biopsy cytology and combined preoperative tests in the diagnosis of breast cancer (1995)
    Springer
    Surgery today 25 (1995), S. 404-408 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311816
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  • 3
    Electronic Resource
    Electronic Resource
    Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer (1995)
    Springer
    Surgery today 25 (1995), S. 874-882 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00311752
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  • 4
    Electronic Resource
    Electronic Resource
    Sudden hemorrhage of the breast caused by breast cancer without skin invasion: Report of a case (1995)
    Springer
    Surgery today 25 (1995), S. 920-922 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00311760
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  • 5
    Electronic Resource
    Electronic Resource
    Gynaecologic effects of Tamoxifen (1995)
    Springer
    Cancer immunology immunotherapy 12 (1995), S. 87-94 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01676708
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  • 6
    Electronic Resource
    Electronic Resource
    Radiation recall in a patient with breast cancer treated for tuberculosis (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 77-78 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00202177
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  • 7
    Electronic Resource
    Electronic Resource
    Cancer awareness and self-examination practices in young men and women (1995)
    Springer
    Journal of behavioral medicine 18 (1995), S. 377-384 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01857661
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  • 8
    Electronic Resource
    Electronic Resource
    Use of sialylated or sulfated derivatives and acrylamide copolymers of Galβ1,3GalNAcα- and GalNAcα- to determine the specificities of blood group T- and Tn-specific lectins and the copolymers to measure anti-T and anti-Tn antibody levels in cancer patients (1995)
    Springer
    Glycoconjugate journal 12 (1995), S. 55-62 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00731869
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  • 9
    Electronic Resource
    Electronic Resource
    Developing gossypol derivatives with enhanced antitumor activity (1995)
    Springer
    Investigational new drugs 13 (1995), S. 181-186 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00873798
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  • 10
    Electronic Resource
    Electronic Resource
    A phase II trial of paclitaxel (Taxol®) as first line treatment in advanced breast cancer (1995)
    Springer
    Investigational new drugs 13 (1995), S. 217-222 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873803
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  • 11
    Electronic Resource
    Electronic Resource
    Effects of vinorelbine on epidermal growth factor-receptor binding of human breast cancer cell linesin vitro (1995)
    Springer
    Investigational new drugs 13 (1995), S. 187-193 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873799
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  • 12
    Electronic Resource
    Electronic Resource
    Abortion and breast cancer risk in seven countries (1995)
    Springer
    Cancer causes & control 6 (1995), S. 75-82 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00051683
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  • 13
    Electronic Resource
    Electronic Resource
    Growth and metastasis of human breast cancers in athymic nude mice (1995)
    Springer
    Clinical & experimental metastasis 13 (1995), S. 3-15 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00144013
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  • 14
    Electronic Resource
    Electronic Resource
    Expression of MHC class I and class II antigens in primary breast carcinomas and synchronous nodal metastases (1995)
    Springer
    Clinical & experimental metastasis 13 (1995), S. 43-48 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00144017
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  • 15
    Electronic Resource
    Electronic Resource
    Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens (1995)
    Springer
    Clinical & experimental metastasis 13 (1995), S. 277-286 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00133483
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  • 16
    Electronic Resource
    Electronic Resource
    An experimental model of leptomeningeal metastases employing rat mammary carcinoma cells (1995)
    Springer
    Journal of neuro-oncology 23 (1995), S. 15-21 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01058455
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  • 17
    Electronic Resource
    Electronic Resource
    Diagnosis and management of spinal metastases from breast cancer (1995)
    Springer
    Journal of neuro-oncology 23 (1995), S. 121-134 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053417
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  • 18
    Electronic Resource
    Electronic Resource
    Response of brain metastases from breast cancer to megestrol acetate: A case report (1995)
    Springer
    Journal of neuro-oncology 24 (1995), S. 299-301 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01052847
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  • 19
    Electronic Resource
    Electronic Resource
    Visual evoked potentials findings in course of paclitaxel doxorubicin combination chemotherapy (1995)
    Springer
    Journal of neuro-oncology 25 (1995), S. 221-225 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053155
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  • 20
    Electronic Resource
    Electronic Resource
    Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy (1995)
    Springer
    Cancer causes & control 6 (1995), S. 283-291 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00051403
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  • 21
    Electronic Resource
    Electronic Resource
    Analysis of estrogen and progesterone receptors on preoperative fine-needle aspirates (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 179-184 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682725
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  • 22
    Electronic Resource
    Electronic Resource
    Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease? (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 77-83 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666494
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  • 23
    Electronic Resource
    Electronic Resource
    Second-line chemotherapy with long-term low-dose oral etoposide in patients with advanced breast cancer (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 185-189 
    Details
    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%).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665790
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  • 24
    Electronic Resource
    Electronic Resource
    Microdissection and microcloning of chromosomal alterations in human breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 95-102 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682717
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  • 25
    Electronic Resource
    Electronic Resource
    Dehydroepiandrosterone concentration in breast cancer tissue is related to its plasma gradient across the mammary gland (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 171-177 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682724
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  • 26
    Electronic Resource
    Electronic Resource
    Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 237-244 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665948
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  • 27
    Electronic Resource
    Electronic Resource
    Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 25-33 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666488
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  • 28
    Electronic Resource
    Electronic Resource
    Body fat distribution in relation to breast cancer in women participating in the DOM-project (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 55-61 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666491
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  • 29
    Electronic Resource
    Electronic Resource
    SH2 domain-containing signaling proteins in human breast cancer (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 85-92 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; signal transduction ; tyrosine kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666495
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  • 30
    Electronic Resource
    Electronic Resource
    MCF-7 breast cancer cells overexpressing transfectedc-erbB-2 have anin vitro growth advantage in estrogen-depleted conditions and reduced estrogen-dependence and tamoxifen-sensitivityin vivo (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 97-117 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665783
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  • 31
    Electronic Resource
    Electronic Resource
    Cutaneous side effects in breast cancer patients treated with cytostatic polychemotherapy and rh GM-CSF: Immune phenomena or drug toxicity? (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 213-219 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689712
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  • 32
    Electronic Resource
    Electronic Resource
    Estrogen receptors in 699 primary breast cancers: A comparison of immunohistochemical and biochemical methods (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 221-228 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689713
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  • 33
    Electronic Resource
    Electronic Resource
    Maintenance of DNA content and erbB-2 alterations in intraductal and invasive phases of mammary cancer (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 253-263 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689717
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  • 34
    Electronic Resource
    Electronic Resource
    Plasma changes in breast cancer patients during endocrine therapy — lipid measurements and nuclear magnetic resonance (NMR) spectroscopy (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 287-297 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713400
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  • 35
    Electronic Resource
    Electronic Resource
    Vinorelbine and the topoisomerase 1 inhibitors: Current and potential roles in breast cancer chemotherapy (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 1-17 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666066
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  • 36
    Electronic Resource
    Electronic Resource
    Polyamine profiles and growth properties of ornithine decarboxylase overexpressing MCF-7 breast cancer cells in culture (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 45-53 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666490
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  • 37
    Electronic Resource
    Electronic Resource
    Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 129-137 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665785
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  • 38
    Electronic Resource
    Electronic Resource
    Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen EM-219 on estrone (E1)-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 147-159 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665787
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  • 39
    Electronic Resource
    Electronic Resource
    Influence of n-3 fatty acids on the growth of human breast cancer cellsin vitro: Relationship to peroxides and Vitamin-E (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 199-212 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689711
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  • 40
    Electronic Resource
    Electronic Resource
    Effect of timing of surgery during the menstrual cycle of premenopausal breast cancer patients (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 279-287 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689719
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  • 41
    Electronic Resource
    Electronic Resource
    With a different voice: Integrating the psychosocial perspective into routine oncology care (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 39-42 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00694743
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  • 42
    Electronic Resource
    Electronic Resource
    Protein kinases in human breast cancer (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 105-114 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00694751
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  • 43
    Electronic Resource
    Electronic Resource
    Aromatase inhibitor development for treatment of breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 19-26 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666067
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  • 44
    Electronic Resource
    Electronic Resource
    Current status of Taxotere® (docetaxel) as a new treatment in breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 39-46 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666069
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  • 45
    Electronic Resource
    Electronic Resource
    Age at menarche and breast cancer risk in nulliparous women (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 55-61 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666071
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  • 46
    Electronic Resource
    Electronic Resource
    Western blotting and isoform analysis of cathepsin D from normal and malignant human breast cell lines (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 211-220 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668211
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  • 47
    Electronic Resource
    Electronic Resource
    Aromatase inhibition with 4-OHAndrostenedione after prior aromatase inhibition with aminoglutethimide in women with advanced breast cancer (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 249-253 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665976
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  • 48
    Electronic Resource
    Electronic Resource
    Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 293-297 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665981
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  • 49
    Electronic Resource
    Electronic Resource
    Recurrence-free survival in breast cancer improved by adjuvant tamoxifen -especially for progesterone receptor positive tumors with a high proliferation (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 23-34 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690181
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  • 50
    Electronic Resource
    Electronic Resource
    Adjuvant tamoxifen for pre- and postmenopausal women with estrogen receptor positive, node positive breast cancer: A randomized study (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 49-53 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690184
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  • 51
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    Electronic Resource
    P-glycoprotein immunostaining correlates with ER and with high Ki67 expression but fails to predict anthracycline resistance in patients with advanced breast cancer (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 61-69 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690186
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  • 52
    Electronic Resource
    Electronic Resource
    Mastopathy of the accessory breast in the bilateral axillary regions occurring concurrently with advanced breast cancer (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 221-224 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668212
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  • 53
    Electronic Resource
    Electronic Resource
    Nonattendance in the Stockholm mammography screening trial: Relative Mortality and reasons for nonattendance (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 267-275 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665978
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  • 54
    Electronic Resource
    Electronic Resource
    High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer: A phase II trial of the Cancer and Leukemia Group B (CALGB) (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 35-40 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690182
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  • 55
    Electronic Resource
    Electronic Resource
    Prognostic significance of heat-shock protein-27 in node-positive breast carcinoma: an immunohistochemical study (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 93-97 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690189
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  • 56
    Electronic Resource
    Electronic Resource
    Biological and clinical role of angiogenesis in breast cancer (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 103-107 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666032
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  • 57
    Electronic Resource
    Electronic Resource
    Cyclical mastopathy and premenopausal breast cancer risk (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 63-73 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666072
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  • 58
    Electronic Resource
    Electronic Resource
    Evaluation of serum tumor markers in patients with advanced or recurrent breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 83-88 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666074
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  • 59
    Electronic Resource
    Electronic Resource
    Chromosome 11q13 markers and D-type cyclins in breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 125-135 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682720
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  • 60
    Electronic Resource
    Electronic Resource
    The relationship of cytoplasmic intermediate filaments and membrane antigens with hormone receptors, nuclear staining density, and mode of stromal invasion in human breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 147-162 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00682722
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  • 61
    Electronic Resource
    Electronic Resource
    Protein tyrosine phosphatase activity as a diagnostic parameter in breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 245-256 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665949
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  • 62
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    Electronic Resource
    Oncologic and cosmetic outcome in patients with breast cancer treated with wide excision, transposition of adipose tissue with latissimus dorsi muscle, and axillary dissection followed by radiotherapy (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 163-171 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668206
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  • 63
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    Electronic Resource
    Prognostic significance of laminin production in relation with its receptor expression in human breast carcinomas (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 195-199 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668209
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  • 64
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    Electronic Resource
    Tumor angiogenesis in breast cancer: Its importance as a prognostic indicator and the association with vascular endothelial growth factor expression (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 193-204 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666040
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  • 65
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    Electronic Resource
    Breast cancer and importance of zygosity determination in triplet sisters (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 315-317 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713403
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  • 66
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    Electronic Resource
    Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 41-48 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690183
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  • 67
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    Electronic Resource
    At convenience and systematic random sampling: effects on the prognostic value of nuclear area assessments in breast cancer patients (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 55-60 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00690185
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  • 68
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    Electronic Resource
    Urokinase receptor in breast cancer tissue extracts. Enzyme-linked immunosorbent assay with a combination of mono- and polyclonal antibodies (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 199-207 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665944
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  • 69
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    Hypotheses: Melatonin/steroid combination contraceptives will prevent breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 257-264 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665950
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  • 70
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    Breast cancer stage at diagnosis: Caucasians versus Afro-Americans (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 195-198 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689710
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  • 71
    Electronic Resource
    Electronic Resource
    Serum lipids and apolipoproteins in women with breast masses (1995)
    Springer
    Breast cancer research and treatment 34 (1995), S. 161-169 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00665788
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  • 72
    Electronic Resource
    Electronic Resource
    The North Carolina Breast Cancer Screening Program: foundations and design of a model for reaching older, minority, rural women (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 7-22 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00694740
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  • 73
    Electronic Resource
    Electronic Resource
    Ha-ras rare alleles in breast cancer susceptibility (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 97-104 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00694750
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  • 74
    Electronic Resource
    Electronic Resource
    Difference in thymidylate synthetase activity in involved nodes compared with primary tumor in breast cancer patients (1995)
    Springer
    Breast cancer research and treatment 35 (1995), S. 157-162 
    Details
    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).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00668205
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  • 75
    Electronic Resource
    Electronic Resource
    Human mammary carcinomas express homologues of rat metastasis-associated variants of CD44 (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 307-313 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713402
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  • 76
    Electronic Resource
    Electronic Resource
    Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 169-180 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666038
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  • 77
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    Electronic Resource
    H-31 human breast cancer cells stimulate type I collagenase production in osteoblast-like cells and induce bone resorption (1995)
    Springer
    Clinical & experimental metastasis 13 (1995), S. 287-295 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00133484
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  • 78
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    Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of United States women (1995)
    Springer
    Cancer causes & control 6 (1995), S. 460-468 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00052187
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  • 79
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    Electronic Resource
    Confirmation of the copy number of chromosome 1 in interphase nuclei from paraffin sections of breast tumours by fluorescencein situ hybridization (1995)
    Springer
    Chromosome research 3 (1995), S. 410-416 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00713890
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  • 80
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    The interface between physical and mental disorders: The need to dismantle the biopsychosocialneuroimmunological model of disease (1995)
    Springer
    Journal of clinical psychology in medical settings 2 (1995), S. 225-231 
    Details
    ISSN: 1573-3572
    Keywords: adherence ; breast cancer ; HIV infection ; immunity ; stress ; transplant ; health psychology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article argues for the necessity of cognitive-behavioral assessment for a thorough understanding of how psychological factors mediate disease process across a wide range of diseases including coronary artery disease, breast cancer, and human immunodeficiency disease. Based on empirical data presented as part of the APA Presidential miniconvention, “To Your Health: Psychology through the Life Span,” the conclusion is that psychological treatment can help extend life. Stress management programs can positively influence adherence to treatment regimens and positively influence the human immune system response during the course of treatment and recovery from illness. Even in the face of life-threatening circumstances such as liver transplantation, Stage II and III breast cancer, and after HIV infection has been diagnosed, the quality of life can be remarkably improved. Physicians and psychologists must work together to produce the beneficial effects of the synergy between mind-body processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01990878
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  • 81
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    Electronic Resource
    Activity of aromatase in breast cancer tissue: Role of the cell substrate (1995)
    Springer
    Bulletin of experimental biology and medicine 120 (1995), S. 1042-1045 
    Details
    ISSN: 1573-8221
    Keywords: aromatase ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The activity of aromatase (estrogen synthetase) in tumor tissue of breast cancer patients was investigated by biochemical and immunohistochemical methods. The detection of medium or high enzyme activity in tumor tissue was virtually the same for both methods. According to immunohistochemical analysis, aromatase activity was localized mainly in malignant epithelial cells, being reliably higher in the tumors of patients in menopause than in those whose cycle was intact. Doubts about the biological role of aromatase in breast cancer tissue may be dispelled if the tissue topography of the enzyme and the individual ratio of epithelial to stromal cellular elements in individual neoplasms of the breast are taken into account.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02444980
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  • 82
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    Electronic Resource
    Proliferative activity of tumor cells as a prognostic factor in breast cancer (1995)
    Springer
    Bulletin of experimental biology and medicine 120 (1995), S. 858-860 
    Details
    ISSN: 1573-8221
    Keywords: breast cancer ; proliferative activity ; Ki-67 ; cellular differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The proliferative activity of 92 breast carcinomas was studied. Statistically significant correlations between the level of proliferative activity and degree of differentiation of tumor cells and nuclear grade were found. Statistically reliable differences in proliferative activity were revealed in the groups of patients under and over 50 years. These facts show that proliferative activity can be used as an individual factor for predicting the aggressiveness of the neoplastic process in patients with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02445975
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  • 83
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    A phase II chemoprevention trial design to identify surrogate surrogate endpoint biomarkers in breast cancer (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 59 (1995), S. 19-24 
    Details
    ISSN: 0730-2312
    Keywords: Biomarkers ; breast cancer ; chemoprevention ; clinical trial ; ductal carcinoma in situ ; Phase II ; retinoids ; tamoxifen ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Surrogate biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of conducting chemoprevention trials. In addition to criteria of sensitivity, specificity, quantifiability, and reproducibility applicable to most potential biomarkers, there are additional specific constraints in developing biomarkers for specific organ sites. In the case of breast tissue, these difficulties include lack of a consensus on the nature of premalignant lesions and the histologic criteria used to define them; even when such a consensus can be evolved, there are limitations in visualizing such lesions without invasive biopsies. Also, knowledge of specific genetic and biochemical changes in premalignant lesions is limited. In addition, the physiology of breast tissue is cyclic; no proven, relevant markers can be studied in a randomly obtained needle aspirate. The earliest determinate lesion that can be recognized in breast tissue is ductal carcinoma in situ (DCIS). At the University of Texas M.D. Anderson Cancer Center, we have initiated a study to develop biomarkers for tamoxifen and 4-hydroxyphenylretinamide by administering one or both of these drugs to women with DCIS or small invasive lesions in the interval between the initial diagnostic core biopsy and definitive surgery. The treatment is to be administered for 2-4 weeks. Proposed biomarkers to be studied include: (a) markers associated with neoplastic phenotypes, e.g., excessive proliferation, alterations of nuclear morphology and angiogenesis; (b) proteins likely to be required for response to the putative chemopreventive agents, e.g., estrogen receptor, nuclear retinoid receptors; (c) markers indicative of intact downstream response pathways, e.g., progesterone receptors; (d) oncogenes and tumor suppressor genes regulated by the proposed chemopreventive agents, e.g. neu, TGF-β; and (e) potential novel markers of genetic instability that could be studied in randomly obtained needle aspirates, i.e., random chromosomal gains and losses in high risk mammary epithelium. The experience gained in designing and conducting this trial is expected to facilitate development of future chemoprevention trials of breast, as well as other organ site cancers.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240590904
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  • 84
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    Insulin receptor overexpression in 184B5 human mammary epithelial cells induces a ligand-dependent transformed phenotype (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 57 (1995), S. 666-669 
    Details
    ISSN: 0730-2312
    Keywords: breast cancer ; insulin ; malignant transformation ; tyrosine kinase ; insulin receptor ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: To determine the role of the insulin receptor overexpression in breast epithelial cell transformation, the 184B5 human breast epithelial cell line was transfected with human insulin receptor cDNA. In two cell lines transfected with and overexpressing human insulin receptors (IR) (223.8 and 184.5 ng IR/106 cells), but not in untransfected cells, insulin binding and tyrosine kinase activity were elevated, and insulin induced a dose-dependent increase in colony formation in soft agar.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240570411
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  • 85
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    An Adaptive Hierarchical Approximation Method on the Sphere Using Axisymmetric Locally Supported Basis Functions (1995)
    Details
    Publication Date: 2014-02-26
    Description: The paper discusses the approximation of scattered data on the sphere which is one of the major tasks in geomathematics. Starting from the discretization of singular integrals on the sphere the authors devise a simple approximation method that employs locally supported spherical polynomials and does not require equidistributed grids. It is the basis for a hierarchical approximation algorithm using differently scaled basis functions, adaptivity and error control. The method is applied to two examples one of which is a digital terrain model of Australia.
    Keywords: ddc:000
    Language: English
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    Identities for Families of Orthogonal Polynomials and Special Functions (1995)
    Details
    Publication Date: 2015-06-01
    Description: In this article we present new results for families of orthogonal polynomials and special functions, that are determined by algorithmical approaches. In the first section, we present new results, especially for discrete families of orthogonal polynomials, obtained by an application of the celebrated Zeilberger algorithm. Next, we present algorithms for holonomic families $f(n,x)$ of special functions which possess a derivative rule. We call those families {\sl admissible}. A family $f(n,x)$ is holonomic if it satisfies a holonomic recurrence equation with respect to $n$, and a holonomic differential equation with respect to $x$, i.\ e. linear homogeneous equations with polynomial coefficients. The rather rigid property of admissibility has many interesting consequences, that can be used to generate and verify identities for these functions by linear algebra techniques. On the other hand, many families of special functions, in particular families of orthogonal polynomials, are admissible. We moreover present a method that generates the derivative rule from the holonomic representation of a holonomic family. % whenever one exists. As examples, we find new identities for the Jacobi polynomials and for the Whittaker functions, and for families of discrete orthogonal polynomials by the given approach. Finally, we present representations for the parameter derivatives of the Gegenbauer and the generalized Laguerre polynomials.
    Keywords: ddc:000
    Language: English
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    Programs for Applying Symmetries of PDEs (1995)
    Details
    Publication Date: 2014-02-26
    Description: In this paper the programs {\tt APPLYSYM}, {\tt QUASILINPDE} and {\tt DETRAFO} are described which aim at the utilization of infinitesimal symmetries of differential equations. The purpose of {\tt QUASILINPDE} is the general solution of quasilinear PDEs. This procedure is used by {\tt APPLYSYM} for the application of point symmetries for either \begin{itemize} \item calculating similarity variables to perform a point transformation which lowers the order of an ODE or effectively reduces the number of explicitly occuring independent variables in a PDE(-system) or for \item generalizing given special solutions of ODEs/PDEs with new constant parameters. \end{itemize} The program {\tt DETRAFO} performs arbitrary point- and contact transformations of ODEs/PDEs and is applied if similarity and symmetry variables have been found. The program {\tt APPLYSYM} is used in connection with the program {\tt LIEPDE} for formulating and solving the conditions for point- and contact symmetries which is described in LIEPDE(1992). The actual problem solving is done in all these programs through a call to the package {\tt CRACK} for solving overdetermined PDE-systems.
    Keywords: ddc:000
    Language: English
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  • 88
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    Simulation und Optimierung einer PC-Fertigung unter Echtzeitbedingungen (1995)
    Details
    Publication Date: 2014-02-26
    Description: Die Business Unit PC in Augsburg ist die zentrale Produktionsstätte der Siemens--Nixdorf Informationssysteme (SNI) AG für Personal Computer sowie für einige Periphärgeräte. Das Werk, entworfen nach modernen CIM/CAI--Konzepten (Computer Integrated Manufacturing/ Computer Aided Industry), wurde 1987 errichtet. Bald zeigte sich jedoch, daß es für ein zu geringes Produktionsvolumen ausgelegt war und einige Komponenten des Systems Engpässe im Produktionsbetrieb darstellen. Das Management suchte nach Möglichkeiten, den Produktionsfluß zu verbessern, ohne teure technische Änderungen am System vornehmen zu müssen. Eine Forschungsgruppe des Konrad--Zuse--Zentrums für Informationstechnik (die ehemals an der Universität Augsburg ansässig war) analysierte, unterstützt von einigen Studenten und Ingenieuren der SNI, den Produktionsfluß und lokalisierte Schwachstellen. Basierend auf diesen Erkenntnissen wurden mathematische Fragestellungen erarbeitet und auf mathematischen Optimierungsverfahren basierende Softwarepakete entwickelt, die jetzt teilweise bei SNI im Einsatz sind. Im folgenden werden einige dieser Fragestellungen, deren Modellierung und mathematische Behandlung beschrieben. Einige der Ansätze, die hier dargestellt werden sollen, sind teilweise schon in Grötschel [Grö92] angesprochen worden.
    Keywords: ddc:000
    Language: German
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  • 89
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    Spirals in Scalar Reaction-Diffusion Equations (1995)
    Details
    Publication Date: 2014-02-26
    Description: Spiral-like patterns are an often observed phenomenon in chemical experiments such as the Belousov-Zhabotinskii reaction. The talk is concerned with a new PDE model whose solutions have the form of rotating spirals. In contrast to previous approaches it is based on a {\em scalar\/} reaction diffusion equation defined on a disk. A particular choice of boundary conditions leads to a non-selfadjoint operator which permits non-trivial dynamics. We study this equation using a combination of equivariant bifurcation theory and numerical simulations. The latter involves the direct simulation of the time dependent system as well as the computation of rotating waves and their stability.
    Keywords: ddc:000
    Language: English
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  • 90
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    A Pseudospectral Chebychev method for the 2D Wave Equation with Domain Stretching and Absorbing Boundary Conditions (1995)
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    Publication Date: 2014-02-26
    Description: In this paper we develop a method for the simulation of wave propagation on artificially bounded domains. The acoustic wave equation is solved at all points away from the boundaries by a pseudospectral Chebychev method. Absorption at the boundaries is obtained by applying one-way wave equations at the boundaries, without the use of damping layers. The theoretical reflection coefficient for the method is compared to theoretical estimates of reflection coefficients for a Fourier model of the problem. These estimates are confirmed by numerical results. Modification of the method by a transformation of the grid to allow for better resolution at the center of the grid reduces the maximum eigenvalues of the differential operator. Consequently, for stability the maximum timestep is $O(1/N)$ as compared to $O(1/N^2)$ for the standard Chebychev method. Therefore, the Chebychev method can be implemented with efficiency comparable to that of the Fourier method. Moreover, numerical results presented demonstrate the superior performance of the new method.
    Keywords: ddc:000
    Language: English
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  • 91
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    0/1-Integer Programming: Optimization and Augmentation are Equivalent (1995)
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    Publication Date: 2014-02-26
    Description: {\def\xnew{x^{\mbox{\tiny new}}}\def\Z{{{\rm Z}\!\! Z}}For every fixed set ${\cal F}\subseteq\{0,1\}^n$ the following problems are strongly polynomial time equivalent: given a feasible point $x\in\cal F$ and a linear objective function $c\in\Z^n$, \begin{itemize} \item find a feasible point $x^*\in\cal F$ that maximizes $cx$ (Optimization), \item find a feasible point $\xnew\in\cal F$ with $c\xnew〉cx$ (Augmentation), and \item find a feasible point $\xnew\in\cal F$ with $c\xnew〉cx$ such that $\xnew-x$ is ``irreducible''\\(Irreducible Augmentation). \end{itemize} This generalizes results and techniques that are well known for $0/1$--integer programming problems that arise from various classes of combinatorial optimization problems.}
    Keywords: ddc:000
    Language: English
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  • 92
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    Testing for Sn-Symmetry with a Recursive Detective (1995)
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    Publication Date: 2014-02-26
    Description: In the recent years symmetric chaos has been studied intensively. One knows which symmetries are admissible as the symmetry of an attractor and which transitions are possible. The numeric has been developed using equivariant functions for detection of symmetry and augmented systems for determination of transition points. In this paper we look at this from a sophisticated group theoretic point of view and from the view of scientific computing, i.e. efficient evaluation of detectives is an important point. The constructed detectives are based on Young's seminormal form for $S_n$. An application completes the paper.
    Keywords: ddc:000
    Language: English
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  • 93
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    Efficient Computation of Orthogonal Polynomials in Computer Algebra (1995)
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    Publication Date: 2015-06-01
    Description: Orthogonal polynomials %like the Chebyshev polynomials can be calculated by computation of determinants, by the use of generating functions, in terms of Rodrigues formulas, by iterating recurrence equations, calculating the polynomial solutions of differential equations, through closed form representations and by other means. In this article, we give an overview about the efficiency of the above methods in Maple, Mathematica, and REDUCE. As a noncommercial package we include the MuPAD system.
    Keywords: ddc:000
    Language: English
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  • 94
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    Enhanced long-term simultation of Hamiltonian systems containing a strong non-convex potential (1995)
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    Publication Date: 2014-02-26
    Description: Many physical systems exhibit rapid motion coupled to a slowly varying motion. Often the rapid motion is associated with a stiff contribution in the potential energy function. In this context, the situation typically considered in the literature is the one with a strictly convex potential. Under some technical assumptions, one can then show that the slow motion is reproduced by a properly constrained system. In this paper we are concerned with a different situation: Often different time-scales can be found because of many local minima and barrier crossing between these minima. We suggest here to replace the detailed motion in the minima and the local barrier crossings by a statistical model which is then coupled to the slow equations of motion over long periods of time. This leads to Langevin type equations of motion subject to an appropriate time transformation.
    Keywords: ddc:000
    Language: English
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  • 95
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    Test sets and inequalities for integer programs: extended abstract (1995)
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    Publication Date: 2014-02-26
    Description: This paper presents some connections between test sets and valid inequalities of integer programs. The reason for establishing such relationships is the hope that information (even partial) on one of these objects can be used to get information on the other and vice versa. We approach this study from two directions: On the one hand we examine the geometric process by which the secondary polytope associated with a matrix $A$ transforms to the state polytope as we pass from linear programs that have $A$ as coefficient matrix to the associated integer programs. The second direction establishes the notion of classes of augmentation vectors parallel to the well known concept of classes of facet defining inequalities for integer programs. We show how certain inequalities for integer programs can be derived from test sets for these programs.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/postscript
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  • 96
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    An Explicit and Symplectic Integrator for Quantum-Classical Molecular Dynamics (1995)
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    Publication Date: 2014-02-26
    Description: This paper presents an explicit and symplectic integrator called PICKABACK for quantum-classical molecular dynamics. This integration scheme is time reversible and unitary in the quantum part. We use the Lie formalism in order to construct a formal evolution operator which then is split using the Strang splitting yielding the symplectic discretization PICHABACK. Finally the new method is compared with a hybrid method in application to two examples: a collinear collision with a quantum oscillator and additionally a photodissociation process of a collinear ArHCI-molecule.
    Keywords: ddc:000
    Language: English
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  • 97
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    Smoothed Molecular Dynamics for Thermally Embedded Systems (1995)
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    Publication Date: 2014-02-26
    Description: This paper makes use of statistical mechanics in order to construct effective potentials for Molecular Dynamics for systems with nonstationary thermal embedding. The usual approach requires the computation of a statistical ensemble of trajectories. In the context of the new model the evaluation of only one single trajectory is sufficient for the determination of all interesting quantities, which leads to an enormous reduction of computational effort. This single trajectory is the solution to a corrected Hamiltonian system with a new potential $\tilde{V}$. It turns out that $\tilde{V}$ can be defined as spatial average of the original potential $V$. Therefore, the Hamiltonian dynamics defined by $\tilde{V}$ is smoother than that effected by $V$, i.e. a numerical integration of its evolution in time allows larger stepsizes. Thus, the presented approach introduces a Molecular Dynamics with smoothed trajectories originating from spatial averaging. This is deeply connected to time--averaging in Molecular Dynamics. These two types of {\em smoothed Molecular Dynamics} share advantages (gain in efficiency, reduction of error amplification, increased stability) and problems (necessity of closing relations and adaptive control schemes) which will be explained in detail.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 98
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    A Free Energy Approach to the Torsion Dynamics of Macromolecules (1995)
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    Publication Date: 2014-02-26
    Description: Based on the concept of free energy, we give a Hamiltonian formulation for the torsion dynamics of macromolecules. The appropriate reaction coordinates for the free energy calculations are defined in terms of soft constraints as introduced in Brooks, B.R., Zhou, J., and Reich, S., Elastic molecular dynamics with flexible constraints, in preparation and Reich, S., Smoothed Dynamics of Highly Oscillatory Hamiltonian Systems, Physica D, to appear, 1995. We consider a few simplifications that allow one to calculate the free energy analytically and to write the corresponding equations of motion as a constrained Hamiltonian system. We also discuss a possible stochastic embedding of the reduced dynamics by means of a generalized Langevin approach.
    Keywords: ddc:000
    Language: English
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  • 99
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    Discontinuous Optimization Problems in Stochastic Integer Programming (1995)
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    Publication Date: 2014-02-26
    Description: Integer stochastic linear programming is considered from the viewpoint of discontinuous optimization. After reviewing solution approaches via mollifier subgradients and decomposition we outline how to base a solution method on efficient pointwise calculation of the objective employing computer algebra.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 100
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    Adaptive h-p approximation procedures, graded meshes and anisotropic refinement for Numerical Quadrature (1995)
    Details
    Publication Date: 2021-03-19
    Description: A set of adaptive algorithms for quadrature on multi-dimensional polyhedral domains is presented. Several kinds of refinement are discussed, covering local improvement of quadrature order and splitting the domain into sub-domains, resulting in isotropic, graded or anisotropic grids. The algorithms are pure local heuristics using no a priori knowledge or tuning parameters. This approach was motivated by results from finite element theory for optimal approximation results. Numerical experiments show the optimality of pure local greedy-like algorithms for singularity-type functions typically occurring in finite element computations.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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