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  • 1995-1999  (10.513)
  • 1985-1989
  • 1965-1969  (5.125)
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  • 1920-1924
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  • 1997  (10.513)
  • 1968  (5.125)
  • Chemistry  (14.676)
  • Physics  (766)
  • Analytical Chemistry and Spectroscopy  (304)
  • apoptosis
  • breast cancer
Materialart
Erscheinungszeitraum
  • 1995-1999  (10.513)
  • 1985-1989
  • 1965-1969  (5.125)
  • 1940-1944
  • 1920-1924
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  • 1
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; prognostic factor ; young age ; survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of age on the prognosis of breast cancer remains controversial. To investigate the role of age, we reviewed 316 patients with stage I or 1I breast cancer. There were 14 patients below 34, 146 between 35 and 49, 115 between 50 and 65, and 41 over 66 years of age. No correlations were observed between age and clinicopathological variables. Breast cancer patients aged 34 or less had a significantly worse survival compared to those in the older age groups. Multivariate analysis also showed younger age to be a significant factor, followed by lymph node status. Therefore, younger age at onset is considered to be an independent prognostic factor.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1436-2813
    Schlagwort(e): rectal cancer ; apoptosis ; hyperther-mochemoradiotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Apoptosis induced in cancer cells by ionizing radiation, hyperthermia, and 5-fluorouracil (5-FU), termed “hyperthemochemoradiotherapy” (HCR), has been well studied in vitro; however, the role of apoptosis in the tumocidal effect of HCR for primary rectal cancers has not yet been clarified. Therefore, we examined the relationship between the therapeutic effect and induction rate of histological apoptosis in 16 patients with rectal cancers after HCR. Numerous Tunel-positive apoptotic cells were found in the tumor tissue after HCR, but few were found in the tumors which had not received HCR. The histological therapeutic effect was closely correlated to the rate of apoptosis. Thus, we suggest that HCR induces a therapeutic effect mainly through apoptosis in human rectal cancers.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; radiosensitivity ; bax ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Bax-a, a splice variant ofbax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weakbax gene expression, were stably transfected with pCX2neobax encoding humanbax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels ofbax-α. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level ofbax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenousbax-α expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; lymph node metastasis ; survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To investigate the impact of the number of involved lymph nodes on survival, we retrospectively reviewed the data for 37 patients with breast cancer and metastases of ten or more lymph nodes who underwent treatment between 1987 and 1995. Based on the number of positive lymph nodes, the patients were allocated to one of three groups. The 5-year disease-free and overall survival rates for all patients were both 53.0%. The 7 patients with 26 or more positive nodes had significantly poorer survival than either the 19 patients with 10–15 nodes, or the 11 with 16–25 nodes, although there were no differences in survival related to the extent of node involvement as defined using the Japanese staging system. Patients with 50%–75% frequency of metastasis, defined as the positive nodes/total resected nodes, had significantly better survival than those with 〈50% or 〉75% frequency. These results indicate that the number of involved lymph nodes is related to survival and that 25 positive nodes is a cutoff point in breast cancer patients with ten or more positive lymph nodes.
    Materialart: Digitale Medien
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  • 5
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; breast conserving surgery ; surgical margin ; frozen section ; local recurrence
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study was conducted to analyze retrospectively the results of performing sector resection on 56 breasts in 54 patients with breast cancer. The glands were resected with a 2-cm tumor-free margin on both lateral sides and the distal side, and with more than a 3-cm tumor-free margin on the nipple side. The frequency of positive resection margins for the cancer cells was 7/56 (12.5%) on the nipple side and 12/46 (26.1%) on the lateral sides, with an overall frequency of 15/56 (26.8%). There were positive resected margins for cancer cells on both the nipple and lateral sides in 4/46 patients (9%) Assuming the equivocal margins were positive for cancer cells, an accurate diagnosis by frozen section examination was made in 51 of the 56 operations (91.1%). Additional resection of the margins was performed in all 20 cases of a positive resected margin for cancer cells according to the diagnosis by frozen section. Thereafter, the resected margins became negative in 13 cases (65%), but remained positive in 7 cases (35%). These results show that performing diagnosis by frozen section of the surgical margins is an effective guide to resecting tumors adequately.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1436-2813
    Schlagwort(e): wild-typep53 ; apoptosis ; papillary carcinoma of the thyroid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A good prognosis is often achieved in patients who have undergone treatment for human papillary carcinoma of the thyroid. On the assumption that this may be partly attributable to an apoptotic tendency of this special type of tumor, we measured DNA fragmentation, cell death by enzymelinked immunosorbent assay (ELISA), and the expression of apoptosis-related genes. DNA fragmentation occurred more extensively in malignant tumor cells than in benign thyroid tumors or normal thyroid tissue, as examined by agarose gel electrophoresis and confirmed by the quantitative method using an ELISA kit. Although only expression of the tumor suppressor gene,p53, was increased in the tumor tissue, no expression of other genes, such asFas, TNF, c-myc, c-fos orbcl-2, was observed in the normal, benign, or malignant tumor tissues, indicating that the roles of these gene functions, if any, were minimal in these tissues. Sincep53 is closely related to cellular apoptosis and no point mutation was observed in the transcripts expressed by malignant cells, apoptosis and/or the production of an angiogenesis inhibitor induced by wild-typep53 molecules may be related to the favorable prognosis of patients treated for papillary carcinoma of the thyroid.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1569-8041
    Schlagwort(e): antiangiogenesis ; apoptosis ; cell differentiation ; lung cancer ; spontaneous remission
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Spontaneous remission of cancer (SR) is defined as a complete or partial, temporary or permanent disappearance of all or at least some relevant parameters of a soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression. We report the case of a 61-year-old man who presented with extensive metatastic disease five months after pneumonectomy for poorly differentiated large cell and polymorphic lung cancer. A vast metastatic tumour mass of the abdominal wall was confirmed histolologically and there was clinical and radiographic evidence of liver and lung metastases. Eight months later, the patient was operated on for a hernia, which had developed in the inguinal biopsy scar and the surgeon confirmed complete clinical SR of the abdominal wall metastases. Again five months later there was no longer any radiologic evidence of liver and lung metastases. Complete remission has persisted more than five years. Histology of the primary and of the abdominal metastases were reviewed by several independent pathologists. SR is an extremly rare event in lung cancer. This is the first documented case of clinically evident visceral metastases of a bronchiogenic adenocarcinoma developing after complete resection of the primary and then showing complete SR. The epidemiology of SR is reviewed and possible mechanisms involved in SR are discussed.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Annals of oncology 8 (1997), S. 3-6 
    ISSN: 1569-8041
    Schlagwort(e): adjuvant therapy ; breast cancer ; high-dose chemotherapy ; metastases
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Breast cancer is the most common female cancer – one woman in 12 will have breast cancer at some stage during her life. Early-stage breast cancer is often curable; however, the prognosis is much worse in patients with multiple lymph node involvement or metastatic disease. The overall survival at five years is approximately 60% in women with positive lymph nodes, decreasing to 27%–44% when more than 10 lymph nodes are involved. After metastatic relapse, the mainstay of treatment is palliative. However, recent advances in supportive care have facilitated investigation into the use of dose-intensive chemotherapy regimens. The advancement of high-dose chemotherapy in breast cancer and results from clinical trials in both metastatic disease and the adjuvant setting are reviewed here. The true benefit of high-dose chemotherapy in breast cancer continues to be investigated. It is hoped that the results of worldwide, randomised clinical trials, due within the next three to five years, will provide a clearer indication of the value of high-dose chemotherapy, its costs and the patients whom it will benefit most.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; high-dose chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 µg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose-limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%–97%), with 22% (95% CI: 3%–41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Springer
    Annals of oncology 8 (1997), S. 939-943 
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; Taxol–anthracycline combination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    Annals of oncology 8 (1997), S. 149-153 
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; quality of sex life ; sexual dysfunction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: This study examined the impact of breast cancer therapyon women's sexuality. Patients and methods: A questionnaire concerning various sexualproblems experienced before and after treatment was anonymously completed by50 women in the outpatient clinic of our hospital's Division of RadiationOncology. To be eligible, subjects had to be disease-free and sexually active.They also had to have undergone surgery at least one year previously and havecompleted CT and/or RT. Fifty-eight percent of the women involved hadundergone mastectomy and 42% had undergone quadrantectomy followed byRT. Results: Ninety percent of the subjects continued sexual activityafter treatment, but there was an increase in the incidence of sexual problemswhich resulted in a slight reduction in the quality of their sex lives.Sixty-four percent of the women experienced an absence of sexual desire and48% low sexual desire, while 38% had dyspareunia, 44%frigidity and 42% lubrication problems. Vaginismus, brief intercourseand female orgasmic disorder were reported by 30% of the subjects.Thirty-six percent suffered from sexual dysfunction before treatment, whichworsened in about 27%, while in 49% of women sexual problemsarose mainly after chemotherapy (26%) or surgery (12%). Aboutone-half experienced changes in the relationship with their partner. Conclusion: Breast cancer patients experienced sexual dysfunction;ours found it easier to discuss the problems with their partner during theirillness (62%) than with doctors and psychologists (15%).
    Materialart: Digitale Medien
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  • 12
    ISSN: 1569-8041
    Schlagwort(e): ATase ; breast cancer ; drug resistance ; PGP ; GPx ; GSH ; GST ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The identification of new factors predicting relapse,outcome and response to systemic therapy in breast cancer is warranted. Themeasurement of biological markers such as drug resistance parameters (DRPs),which are part of the phenotype of malignant cells and contribute toresistance to anti-cancer drugs may be a possibility, which may ultimatelylead to improvement of therapeutic results. Patients and methods: The level of glutathione (GSH), activities ofglutathione-S-transferase (GST), glutathione-peroxidase (GPx),06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) weremeasured in tumor and adjacent tumor free tissue samples from 89 consecutive,untreated females with breast cancer and correlated with clinical andprognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients,22 patients had locally advanced (LABC) and 11 patients metastatic breastcancer. Results: All DRPs showed significantly higher expression in tumorthan in tumor free tissues. GPx was positively correlated with GST (R = 0.3, P = 0.0048) and with GSH (R = 0.5, P = 0.0001) in tumor as wellas in normal tissue. GST activity was significantly higher in EBC than in LABCor metastatic breast cancer ( P = 0.02). GSH level was significantlyhigher in grade 1 than in grade 2 or grade 3 tumors ( P = 0.01). Whenclinical characteristics were related to the level of DRP, ‘high’ GSH wasassociated with age 〉60 years ( P = 0.01) in EBC, and with grade1–2 tumors ( P = 0.05) in LABC. No differences in OS were apparentbetween groups of ‘high’ and ‘low’ DRP-expression. However, the four-yearestimated disease-free survival of EBC tended to be higher in patients with‘high GST ( P = 0.10) and of LABC in patients with ‘high’ GPx levels( P = 0.06). Conclusion: We conclude that ‘high’ levels of DRP in tumor tissue ofbreast cancer patients are part of the initial phenotype of the malignantcells. Due to its high prevalence (83% in EBC, 100% in primarilymetastatic breast cancer), PGP did not add to prognostic information. Highlevels of GSH, GST and and GPx were associated with favorable clinicalcharacteristics and good prognosis, whereas low levels of GSH and GST activitywere associated with more aggressive or more advanced disease.
    Materialart: Digitale Medien
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  • 13
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; clinical efficacy ; endocrine activity ; vorozole
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Aminoglutethimide was the first aromatase inhibitor to beused successfully in breast cancer patients. However, this drug alsoinhibits mineralcorticoid and glucocorticoid synthesis, making co-medicationwith corticosteroids necessary, and it is often poorly tolerated. Theprimary objective of this trial was to evaluate the clinical efficacy andtolerability of vorozole, a new non-steroidal oral aromatase inhibitor, inpostmenopausal breast cancer patients. The secondary objective was toevaluate the pharmacodynamic activity of the drug. Subjects and methods: Thirty-four postmenopausal patients previouslytreated with tamoxifen in the adjuvant setting and/or for advanced diseasewere treated with vorozole, 2.5 mg once daily. Patients were monitored withrespect to treatment efficacy and safety. Hormonal evaluations wereperformed at baseline and during the course of treatment in order toevaluate the pharmacodynamic efficacy and safety of vorozole. Results: According to UICC criteria, there were seven responders, onecomplete and six partial, for an overall response rate of 21%(95% confidence interval (CI) 9%–38%). The medianduration of response was 9.6 months (95% CI 4.6–0), the mediantime to progression for the entire group was 4.7 months (95% CI2.9–6.6) and the median survival time was 29.7 months (95% CI19.1–0). Tolerability was excellent to good in 97% of thepatients. Oestradiol and oestrone levels were suppressed to the limit ofdetection of the assays used. No effect was observed on the other endocrineparameters. Conclusions: Our results suggest that vorozole is an effective and safedrug for the treatment of advanced postmenopausal breast cancer followingtamoxifen failure.
    Materialart: Digitale Medien
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  • 14
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; chemotherapy ; fluorouracil ; folates ; vinorelbine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Vinorelbine, is an active drug in the treatment of metastatic breast cancer and has a favorable toxicity profile. Its combination with other effective and well-tolerated cytotoxics may thus be beneficial. We investigated the therapeutic effect of a combination of vinorelbine plus 5-fluorouracil and folinic acid as first-line treatment in patients with metastatic breast cancer. Patients and methods: Forty-five patients with advanced or metastatic breast cancer were enrolled in this phase I–II study and treated with 5-fluorouracil (350 mg/m2 i.v. on day 1 to 3), folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine given on days 1 and 3 at the dose of 25 mg/m2 (dose level 1), or 30 mg/m2 (dose level 2). Therapy was given on an outpatient basis every three weeks. Results: Phase I: Dose limiting toxicity (DLT) occurred at the second dose level of vinorelbine (30 mg/m2), with two out of three patients developing severe constipation (‘ileus-like syndrome’ grade 4), and fever (grade 2). Consequently, the dose evaluated in the phase II study was 25 mg/m2. Phase II: Objective responses were observed in 24 of 39 evaluable patients (95% confidence interval (95% CI), 47% to 77%). There were seven complete responses (18%), 17 partial responses (44%), and for nine patients (23%) disease was stable. Only six patients (15%) experienced disease progression. The median response duration was 10 months (range 6 to 24+) and the median time to progression was eight months (range 2 to 24+). Granulocytopenia was the most frequently observed side effect, with a grade 4 nadir being observed in 30 patients (77%), with four hospital admissions due to febrile neutropenia. Nausea, vomiting, and anorexia were mild to moderate and reported by less than half of the patients. Alopecia was moderate and occurred in about one-third of the patients. The other side effects were mild and easily manageable. Conclusions: This effective combination chemotherapy of vinorelbine, 5-fluorouracil and folinic acid is comparable to other first-line regimens in terms of efficacy, and is subjectively well tolerated, thus deserving a test in randomized trials in the advanced and adjuvant settings.
    Materialart: Digitale Medien
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  • 15
    ISSN: 1569-8041
    Schlagwort(e): adjuvant therapy ; breast cancer ; cross-cultural issues ; linear analogue self-assessment (LASA) scales ; quality of life ; randomized controlled trials
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background and purpose: The International Breast Cancer Study Group (IBCSG) has developed an approach for assessing the impact of adjuvant therapy on quality of life (QL) within the framework of international, multilingual clinical trials. The major steps are summarized. Conceptual, methodological and practical issues are discussed with reference to results of two trials closed to accrual (IBCSG VI, VII) and one subsequent ongoing trial (IBCSG IX). Patients and methods: QL was assessed in pre- and postmenopausal patients with operable breast cancer. Various single-item linear analogue self-assessment (LASA) scales were used as indicators of components of QL, including global indicators of well-being, functioning and health perception, and specific indicators of symptoms of disease and treatment. In trials VI and VII, QL was assessed at baseline, during adjuvant treatment and follow-up, and at recurrence. Based on this experience, the QL form was revised for subsequent trials and further investigated in a subsample of patients randomized into trial IX. Results: In trials VI and VII, the QL indicators were responsive to the impact of biomedical factors at baseline, various adjuvant treatments, changes over the first 18 months, and recurrence. In trial IX, the revised QL form was well accepted by patients and staff. Completing this form did not exceed five minutes. QL differences between on and off cytotoxic treatment strengthen the claim that these measures are responsive. Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators. Conclusion: Results from two trials closed to accrual and an ongoing trial confirm the feasibility, validity and clinical relevance of the IBCSG approach for studying the impact of adjuvant breast cancer therapy on QL in international clinical trials.
    Materialart: Digitale Medien
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  • 16
    ISSN: 1432-1335
    Schlagwort(e): RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1×106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers: there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
    Materialart: Digitale Medien
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  • 17
    ISSN: 1436-2813
    Schlagwort(e): breast cancer ; chemosensitivity ; bax ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Bax, one of thebcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weakbax gene expression, were stably transfected withpCX2neo bax, encoding humanbax; and two unique clones,MCF-7/bax-1 andMCF-7/bax-2, that expressed different levels ofbax were generated. Sensitivity to cisplatin (CDDP) and etoposide (VP-16) was examined and each stable transfectant was more sensitive to these agents than the parental MCF-7 cells. The degree of enhancement in sensitivity to these anticancer agents was dependent on the expression level ofbax. The enzyme-linked immunosorbent assay (ELISA), which quantifies DNA damage, demonstrated that this sensitization was due to apoptosis. Thus, we suggest that exogenousbax-α overexpression may be one of the factors determining cellular chemosensitivity in MCF-7 breast cancer cells and that it could be applied therapeutically to enhance chemosensitivity in breast cancer cells.
    Materialart: Digitale Medien
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  • 18
    ISSN: 1436-2813
    Schlagwort(e): bcl-2 protein ; apoptosis ; esophageal carcinoma ; basaloid carcinoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the present study, the expression of bcl-2 protein in esophageal squamous cell carcinoma (SCC) and basaloid carcinoma (BC) was immunohistochemically examined, and its relation to tumor progression and postoperative survival was determined in SCC.A total of 42 SCC and 4 BC tumor samples were fixed with formalin, embedded in paraffin, and stained using monoclonal bcl-2 protein antibody, clone 124. Immunoreactivity was semiquantitatively scored, and the staining results were compared with the pathologic features and survival rates. The cytoplasm of basal cells from the normal esophageal epithelium was stained. In some well- and moderately differentiated SCCs, bcl-2 protein-positive reaction was observed in the peripheral part of the tumor cord, but in poorly differentiated SCC, the cells were weakly or hardly stained. However, in BC, the cells were strongly stained. The immunoreactivity was positive in 45.2% of the SCCs and all of the BCs. There were no significant differences in pathological features or patient survival between the bcl-2 protein-positive and protein-negative SCCs. In conclusion, the expression was not related to tumor progression and had no prognostic significance in SCC. Conversely, BC had strong immuno-histochemical expression, probably associated with the differentiation of carcinoma cells simulating the basal cells of the esophagus.
    Materialart: Digitale Medien
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  • 19
    ISSN: 0942-0940
    Schlagwort(e): Aneurysm ; anti-single-stranded DNA antibody ; apoptosis ; DNA fragmentation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Pathological specimens were collected from 14 unruptured and 13 ruptured aneurysms at the time of clipping and studied in order to assess the underlying mechanism of rupture by investigating degeneration of the aneurysmal wall and possible involvement of apoptosis. Immunohistochemistry with anti-actin antibody showed few smooth muscle cells in the ruptured aneurysms and replacement of the muscularis layer by a fibro-hyalin tissue. However, at least one layer of smooth muscle cells was clearly observed in the unruptured aneurysms. Thus, smooth muscle cells in the wall of the ruptured aneurysms were much more degenerated than those in the wall of unruptured aneurysms. In addition, unruptured aneurysms with an angiographically smooth wall showed well-layered positive staining for anti-smooth muscle actin antibody while those with irregular shapes rarely reacted. We found, for the first time, evidence of DNA fragmentation in the aneurysmal wall. Apoptotic bodies were detected by means of a terminal transferase (TdT)-mediated dUTP biotin nick end labelling technique (TUNEL) and an anti-single-stranded DNA antibody in 54% (7/13) of the ruptured aneurysms. In contrast, apoptotic bodies were found in only 7% (1/14) of the unruptured cases. These results suggest that apoptotic cell death might be involved in the rupture of aneurysms.
    Materialart: Digitale Medien
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  • 20
    ISSN: 1432-1335
    Schlagwort(e): Key words RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1 × 106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers; there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    Annals of oncology 8 (1997), S. 223-225 
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; diet ; genistein ; isoflavones ; soybean ; tyrosine kinase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The study reviews the anticancer properties of naturalisoflavones which occur in especially high concentration in soybeans. Itconsiders the suitability of soybean products for clinical trials aiming toreduce the progression of breast cancer. Methods: Evidence is reviewed that plant isoflavones such asgenistein show cytostatic activity against human mammary cancer cell linesin vitro and can also suppress carcinogen-induced mammary cancer inyoung and mature rats. Results: Plant isoflavones are converted in the bowel to compoundswith potential antioestrogenic and antioxidative properties. These compoundsshow cytostatic activity for both oestrogen receptor-positive and negativehuman mammary cancer cell lines, and also inhibit growth and progress of therat mammary cancer model. The high content of soybean products in the diet ofAsian women has been postulated as one reason for their relatively low breastcancer incidence. Conclusion: Preclinical studies suggest that soybean products begiven priority for clinical trials in breast cancer protection. A pilot studycould test soy protein supplements as long-term adjuvant dietary treatmentafter primary surgery for early breast cancer, looking for a decrease in therisk of recurrence or of second primary tumours.
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  • 22
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; chemotherapy ; platelet-derived endothelial cell growth factor ; prediction ; thymidine phosphorylase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Thymidine phosphorylase (TP) catalyses the reversiblephosphorylation of thymidine to thymine and 2-deoxyribose-1-phosphate. Highexpression of TP in cell lines potentiates the effects of the cytotoxic drugs5-fluorouracil and methotrexate, both of which are used in thecyclophosphamide, 5-fluorouracil and methotrexate (CMF) treatment regimen ofbreast cancer. Patients and methods: We therefore examined the expression of thisenzyme in 328 invasive breast carcinomas using immunohistochemistry andassessed whether the expression of this enzyme by the tumour predicts patientresponse to CMF in node-positive patients. Results: Whereas no significant difference in either relapse-freesurvival (RFS) (P = 0.2) or overall survival (OS) (P = 0.07) wasobserved between TP-negative and -positive tumours in non-treated patients,there was a significant increase in both RFS (P = 0.02) and OS (P = 0.02) inpatients treated with CMF in TP-positive compared with TP-negativetumours. A multivariate analysis of the 134 node-positive patientsdemonstrated that in ductal carcinomas, TP was an independent variable for OS. Conclusions: This pilot study suggests that patients with TP-positivetumours have a significant survival benefit when treated with CMF and supportsthe hypothesis that TP enhances tumour sensitivity to the anti-metabolites5-fluorouracil and methotrexate.
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  • 23
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; conservative treatment ; local recurrence ; risk factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Risk factors for local recurrence after breast-conservingtreatment of early breast cancer have not previously been evaluated insettings where mammography has been a major pathway to diagnosis of bothprimary tumour and recurrences, or in patients treated surgically by a formalsector resection. Patients and methods: Three hundred eighty-one women with stage Iprimary breast cancer were randomised after a standardised sector resectionto either a course of postoperative radiotherapy to 54 Gy to the breast (XRTgroup) or to surgery alone (non XRT group). At five years, 43 localrecurrences, six of them in the XRT group, appeared. Patient characteristicscollected from the medical records, histopathological characteristicsdetermined by re-examination of slides, and mammographic characteristcs fromthe pre-operative mammograms were evaluated as risk factors for recurrence byunivariate and multivariate Cox proportional hazards models. Results arereported as relative hazards (RH) with 95% confidence intervals(95% CI). Results: In the univariate analysis comedo cancer, RH 3.5 (95%CI 1.8–6.7), lobular cancers RH 2.8 (95% CI 1.1–7.1),mammographic appearance as circular/oval shaped density, RH 2.3 (95%CI 1.1–4.5), and mammographic appearance as a stellate lesion withmicrocalcifications inside the lesion, RH 3.8 (95% CI 1.1–13.0)were identified as risk factors for local recurrence. Age, with a RH of 0.97(95% CI 0.94–0.99) for each increasing year was inverselyassociated with risk. A multivariate analysis, which also took postoperativeradiotherapy into account, only showed comedo cancers with a RH 2.6(95% CI 1.3–5.0) and mammographic appearance of a stellate lesionwith microcalcification inside the lesion RH 4.5 (95% CI1.1–17.6) to be statistically significant. The estimates for age RH 0.98(95% CI 0.95–1.0) and lobular cancers RH 2.5 (95% CI0.98–6.6) were marginally changed, with widened CIs. Patients 〉 60years of age, without comedo or lobular carcinomas were found to be at lowrisk (5.9% at five years in Kaplan–Meyer estimate) of localrecurrence, even without postoperative radiotherapy. Conclusion: Low age, comedo and lobular cancers and mammographicappearance of the tumour as a stellate lesion with microcalcifications insidethe lesion indicate an increased risk for local recurrence after sectorresection in stage I tumours at five years. Patients 〉60 years of agewithout comedo or lobular cancers are at low risk for local recurrence at fiveyears even without postoperative radiotherapy.
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  • 24
    ISSN: 1569-8041
    Schlagwort(e): advanced disease ; aromatase inhibitors ; breast cancer ; formestane
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: In postmenopausal breast cancer (BC) patients, tamoxifen (TAM)is frequently used in first-line therapy, and for those relapsing under TAM,aromatase inhibitors would be the drug of choice. Formestane, a new aromataseinhibitor, has been demonstrated to be as effective as TAM in first-linetherapy. This trial was carried out to investigate the pharmacokinetics andantitumor activity of two formestane doses in BC patients at first relapse,as well as their effects on estrogen levels, evaluated by means of a newanalytical method. Patients and methods: One hundred fifty-two postmenopausal BC patients wererandomly given formestane 250 mg or 500 mg intramuscularly every two weeks.The blood samples for estrogen measurements were taken on the first day oftherapy, at 4 and 10 weeks, and every 12 weeks thereafter. Tumor response wasfirst evaluated after 2.5 months, and then every three months. Results: Seventy-three patients received formestane 250 mg and 79 received500 mg. After four weeks, plasma estrone, estradiol and estrone sulphatelevels were significantly (P〈0.001) suppressed in both groups. The overallresponse rates were 30% and 40% on 250 mg and 500 mg,respectively. Conclusions: Both of the formestane doses are effective in reducing plasmaestrogen levels in BC patients at first relapse, and the new analytical methodimproved the quality of results. The antitumor response was highlysatisfactory.
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  • 25
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; cyclophosphamide ; G-CSF ; paclitaxel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The toxicity profile of prolonged infusions of paclitaxel incombination with cyclophosphamide in metastatic breast cancer has already beendefined. The objective of this dose-finding study was to determine the maximumtolerable doses (MTDs) of shorter (three-hour) infusions of paclitaxel incombination with i.v. bolus cyclophosphamide in patients who had previouslyreceived a maximum of one chemotherapy for advanced breast carcinoma. The MTDof the same regimen with granulocyte colony-stimulating factor (G-CSF) supportwas then established. Patients and methods: Eighty women with metastatic breast cancer receiveda total of 352 fully evaluable courses of therapy. The starting doses werepaclitaxel 135 mg/m2 and cyclophosphamide 750mg/m2 given every three weeks. At least three patients weretreated at each dose level and if there were dose-limiting toxic effectsduring the first cycles three additional patients were entered. G-CSF support(5µg/kg s.c.) was added to the second cycle if specific dose-limitingtoxicitieshad occurred during the first cycle. The MTD was defined as the dose level atwhich more than two of six patients presented dose-limiting toxicities duringthe first cycle. Results: Febrile neutropenia (n = 4) and severe thrombocytopenia (n = 1)defined the MTDs of paclitaxel as 200 mg/m2 and ofcyclophosphamide as 2,000 mg/m2, with or without G-CSF inpatients with and, respectively, without prior chemotherapy for advanceddisease. Non-hematologic toxicity was moderate. Recommended doses were 200mg/m2 of paclitaxel and 1,750 mg/m2 ofcyclophosphamide with or without G-CSF in patients with and, respectively,without prior chemotherapy. The overall response rate was 25% and50%, respectively, in patients with and without prior chemotherapy formetastatic disease. Complete remissions (9%) were reported only inpatients without prior chemotherapy; antitumour activity in women withanthracycline-resistant disease, with an 8% response rate (95%CI: 1%–26%), was poor. Conclusions: Paclitaxel at 200 mg/m2 and cyclophosphamideat 1,750 mg/m2 can be safely administered every three weeksto women with advanced breast cancer. The moderate antitumour activityobserved with the schedule tested argues against its use as initial therapyfor advanced breast cancer.
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  • 26
    ISSN: 1569-8041
    Schlagwort(e): breast cancer ; conservative treatment ; cost-effectiveness ; randomized trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Cost-effectiveness of routine postoperative radiotherapyafter breast-conserving surgery has not been prospectively evaluatedearlier. In times of rationing of medical resources, valid assessments ofcost-effectiveness are important for rational allocation of resources. Purpose: Cost and cost-effectiveness of routine postoperativeradiotherapy was calculated in a prospective randomized trial comparingsector resection plus axillary dissection with (XRT group) or without(non-XRT group) postoperative radiotherapy in breast cancer stage I. Threehundred eighty-one patients were included. After a median follow-up of fiveyears 43 local recurrences, six of them in the XRT-group occurred (P 〈0.0001). No difference in regional and distant recurrence (P = 0.23) orsurvival (P = 0.44) was observed. Patients and methods: Direct medical costs as well as indirect costs interms of production lost during the treatment period and travel expenseswere estimated from data in the medical records and the national insuranceregistry of each patient. Average costs of different treatment activitiesand measures were estimated for the XRT-group and the non-XRT grouprespectively. From these estimates differences in costs and effectivenessbetween the groups were calculated and marginal cost-effectiveness ratioswere estimated. For the construction of QALYs each life-year wasquality-adjusted by a utility value depending on which health state thepatient was considered to perceive. Results: Taking into account the cost of primary treatment, the cost offollow-up, the cost of treatment of a local recurrence, travel expenses andindirect costs (production lost) excluding costs for treatment of regionaland distant recurrence the cost per avoided local recurrence at five yearswas SEK 337,727 ($44,438, £27,018). Adjustment for quality of life showed a cost for every gained QALY to beSEK ∼1.6 million, ($210,526, £128,000), range SEK0.2–3.9 million ($26,315–513,158;£16,000–312,000). Conclusion: The cost of routine postoperative radiotherapy after sectorresection and axillary dissection in breast cancer stage I per avoided localrecurrence and gained QALY is high. The cost per gained QALY show greatvariation depending on utility value, which in this study was derived fromexternal observers and not from the patients themselves. These results stressthe importance of identifying risk factors for local recurrence, betterunderstanding of impact on quality of life of a local recurrence and addingcost evaluations to clinical trials in early breast cancer.
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  • 27
    ISSN: 1569-8041
    Schlagwort(e): adjuvant chemotherapy ; breast cancer ; menstrual cycle ; premenopausal ; surgery
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: It has been postulated that breast cancer surgery performedduring the follicular phase of the menstrual cycle is associated with pooreroutcome. Patients and methods: We tested this hypothesis by evaluatingdisease-free survival (DFS) for 1033 premenopausal patients who receiveddefinitive surgery either during the follicular phase (n = 358) or theluteal phase (n = 675). All patients were enrolled in a randomized trialconducted between July 1986 and April 1993. All had node positive breastcancer and randomization was stratified by estrogen receptor (ER) status.All patients received at least three cycles of adjuvant cyclophosphamide,methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. Results: Patients who underwent definitive surgery for breast cancer inthe follicular phase had a slightly worse disease-free survival than thoseoperated on during the luteal phase (five-year DFS percentage: 53%versus 58%; hazard ratio, 1.13; 95% confidence interval (CI),0.94–1.38; P = 0.20). The effect was significantly greater for thesubpopulation of 300 patients with ER-negative primaries (P = 0.02interaction effect; five-year DFS percentages 42% vs. 59%;hazard ratio 1.60; 95% CI, 1.12–2.25; P = 0.008). The effect oftiming of surgery diminished for analyses based on lesser surgicalprocedures, e.g., excisional biopsies. In particular, no effect of timingwas observed for fine needle aspiration procedures. Conclusions: Surgical procedures which are more extensive than a fineneedle aspiration biopsy might be associated with worse prognosis if conductedduring the follicular phase of the menstrual cycle. This phenomenon was seenpredominantly for high risk breast cancer with low levels or no estrogenreceptors in the primary tumor.
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  • 28
    ISSN: 1569-8041
    Schlagwort(e): apoptosis ; chromogranin ; gastrointestinal tumors ; lanreotide ; neuroendocrine ; positron emission tomography ; U-5-HIAA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: Neuroendocrine tumors usually present with inoperable metastatic disease and severe hormonal symtoms. Specific chemotherapy, alpha-interferon and the somatostatin analog octreotide are established therapies in these patients but all of them eventually fail. Other somatostatin analogs, e.g., RC-160 and lanreotide, are currently being studied in different doses and modes of administration. Patients and methods: Nineteen patients with advanced neuroendocrine gastrointestinal tumors [13 carcinoids and six endocrine pancreatic tumors (EPT)], liver metastases being present in 18, most of them heavily pretreated, were included. Seventeen out of 18 patients had somatostatin receptors demonstrated by octreotide scintigraphy. Lanreotide was given as four daily subcutaneous injections, starting with 750 µg/d, then increasing every week up to 12,000 µg/d after six weeks, a dose which was maintained, if tolerated, for 12 months, or until progression. Results: There was a significant tumor size response (〉50%) in one patient (5%), whereas 12 patients (70%) had tumor stabilization for 12 months. Bichemical tumor markers were significantly reduced at six months (urinary 5-hydroxyindoleacetic acid and plasma chromogranin) and 12 months (chromogranin) and the overall biochemical response rate was 58% with this high dose of lanreotide. Adverse events were observed and four patients stopped the treatment due to adverse events. Studies of tumor biopsies before and during treatment indicated induction of apoptosis in patients with tumor stabilization and biochemical response. Conclusion: High-dose treatment with lanreotide (12,000 µg/d) produced tumor size response in 5%, stabilization in 70% and a biochemical response in 58% of patients. These results should be related to the advanced stage of the disease as indicated by the mean duration of disease of more than four years, but they do not appear to be better than those achieved with standard doses of somatostatin analogs. However, in responding patients we observed induction of apoptosis in the tumors, a phenomenon not seen with regular doses of somatostatin analogs, but often produced by chemotherapeutic agents.
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 167 (1997), S. 169-177 
    ISSN: 1573-4919
    Schlagwort(e): tamoxifen ; interferon ; gene expression ; breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The molecular basis for the enhanced growth inhibition of MCF-7 human breast cancer xenografts by a combination of human interferon-β (IFN-β) and tamoxifen was investigated. Treatment of MCF-7, MDA-MB-231, and BT-20 cells with the combination of IFN-β and tamoxifen resulted in enhanced antiproliferative effects in vitro. Treatment with the combination of IFN-β and tamoxifen enhanced the expression of several IFN-β-inducible genes in human breast carcinoma cell lines relative to levels induced by IFN-β alone. Tamoxifen alone did not induce transcription of IFN-stimulated genes (ISGs). Augmentation of ISG expression by the combination of IFN-β and tamoxifen was noted in breast tumor cell lines irrespective of their functional estrogen receptor (ER) status or their dependence on estradiol for growth, suggesting that upregulation of ISGs was independent of ER status. Enhancement of IFN-stimulated gene expression by tamoxifen occurred at the transcripti onal level. Expression of transfected reporter genes under the control of IFN-α/β regulated promoters was also enhanced in IFN-β and tamoxifen-treated cells. Similarly, transcriptional induction of chimeric reporter plasmids driven by an IFN-γ inducible promoter (GAS; IFN-γ activated site) was also enhanced by the combination of IFN-γ and tamoxifen. In tamoxifen treated cells, IFN-β and IFN-γ readily activated transcription factors ISGF-3 and GAF, respectively. Therefore, augmentation of ISG expression by tamoxifen is an early event in the antitumoral activity of this drug combination. (Mol Cell Biochem 167: 169-177, 1997)
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    Molecular and cellular biochemistry 166 (1997), S. 183-189 
    ISSN: 1573-4919
    Schlagwort(e): calcium transport ; DNA topoisomerase II inhibitor ; apoptosis ; DNA fragmentation ; rat liver nuclei
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The effect of various inhibitors of DNA topoisomerase II, which has been shown to induce apoptotic cell death, on Ca2+ transport in isolated rat liver nuclei was investigated. Ca2+ uptake and release were determined with a Ca2+ electrode. The presence of aurintricarboxylic acid (ATA; 10-6 to 10-4 M), etoposide (10-4 M), genistein (10-5 and 10-4 M) or amsacrine (10-4 M) in the reaction mixture caused a significant increase in Ca2+ release from the nuclei. Also, these compounds (10-4 M) significantly inhibited Ca2+ uptake by the nuclei. However, the presence of ATA (10-5 and 10-4 M) in the enzyme reaction mixture did not significantly inhibit Ca2+-ATPase activity, which is involved in the nuclear Ca2+ uptake, in the liver nuclei, while etoposide (10-4 M), genistein (10-4 M) and amsacrine (10-4 M) appreciably decreased the enzyme activity. Meanwhile, addition of Ca2+ clearly activated DNA fragmentation in the liver nuclei. The Ca2+ activated DNA fragmentation was significantly prevented by the presence of etoposide, genistein and amsacrine with the concentrations of 10-5 and 10-4 M in the reaction mixture, although ATA (10-5 and 10-4 M) had no effect. The present study demonstrates that some apoptosis inducible compounds used can influence on Ca2+ transport system in isolated rat liver nuclei, suggesting a decrease of nuclear Ca2+ level involved in nuclear functions. (Mol Cell Biochem 166: 183-189, 1997)
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  • 31
    ISSN: 1573-4919
    Schlagwort(e): aurintricarboxylic acid ; breast cancer ; p53 tumor suppressor protein ; phenanthroline ; rifampicin ; T47D cells
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract We have investigated the influence of three structurally different but functionally related compounds [1, 10 ortho-phenanthroline (phenanthroline), Rifampicin and aurin tricarboxylic acid (ATA)] on the rate and the extent of proliferation of progesterone-responsive T47D human breast cancer cells. These compounds have previously been used in this laboratory and have been shown to modulate properties of nucleic acid binding proteins. Because p53 and the progesterone receptor (PR) are both DNA binding proteins that appear to regulate proliferation of breast cells, alterations in T47D cell p53 and PR levels were examined to determine their relevance in cell proliferation. T47D cells were grown in the absence of phenol red and in the presence of 5% fetal calf serum with or without charcoal stripping in the presence of the inhibitors. The rate of proliferation of cells grown in Rifampicin containing medium exhibited nearly 70% inhibition. Phenanthroline, a known metal chelator, was an effect ive inhibitor of proliferation at 3 mM reducing the cell number by more than 75%. ATA (0.24–2.4 µg/ml) inhibited the growth of the cells by nearly 50%. Analysis of the mechanism of action of these compounds revealed that treatment with these compounds caused specific changes in the molecular composition of T47D cell PR. Whereas ATA caused increased stability of PR isoforms, Rifampicin induced a upshift in the mobility of PR in SDS gels – a phenomenon associated with hyperphosphorylation of steroid receptors (SRs). Phenanthroline treatment (〉 2 mM) caused a complete down-regulation of PR and the tumor suppressor protein, p53. The downregulation of p53 paralleled the changes in the molecular composition of PR. We propose that the inhibition of T47D cell proliferation by phenanthroline, Rifampicin and ATA results from a number of cellular changes that include regulation of p53 and PR. (Mol Cell Biochem 175: 81–89, 1997)
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    Boundary layer meteorology 85 (1997), S. 197-222 
    ISSN: 1573-1472
    Schlagwort(e): Turbulence ; Chemistry ; Closure ; Convective boundary layer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Geologie und Paläontologie , Physik
    Notizen: Abstract We study the interactions of chemistry and turbulent mixing of tracersin the convective boundary layer with a second-order closure model,including higher order chemistry terms. In order to limit the number of predictive equations we prescribe the profiles for ¯w¯Θ, ¯w¯θ ¯θ and the lengthscale l. However, for model validation we treat temperature and humidity asinert tracers, and compare the results with profiles observed during theAir Mass Transformation Experiment, and with similarity expressions for thesurface layer. We find good agreement of the mean profiles, but the (co-)variances are slightly underpredicted. Furthermore, the model usesdiagnostic equations expressing third moments of concentration in terms ofsecond moments and their vertical derivatives. They are compared withlarge-eddy model results, showing good agreement and, therefore, thesimplifications are justified. The model is applied to the transport of two gases subject to one bimolecular reaction. The importance of concentration correlations on themean transformation rate is studied. For two gases diffusing in oppositedirections we find for moderate and fast chemistry a 50% and90% decreased transformation rate due to the negatively correlatedconcentrations. These values are similar to large-eddy results of Schumannand Sykes et al. For two bottom-up tracers we find that the covariance ofboth reactive species is either positive or negative, increasing or reducingthe effective transformation rate depending on the Damköhler number (the ratio of the turbulent and the chemistry timescale). A significantdirect influence of chemistry on the flux divergence is found in bothcases. According to the model the effective transport to mid-levels of theboundary layer is increased when two reactive tracers diffuse in oppositedirections, and decreased in the case of two bottom-up tracers.
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  • 33
    ISSN: 1573-2592
    Schlagwort(e): HIV/AIDS ; costimulatory molecules ; apoptosis ; cell survival genes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Progression to AIDS in asymptomatic HIV-infected individuals is characterized by a gradual but progressive loss of CD4+ T cells. While the mechanisms underlying this decline are currently unknown, recent evidence suggests that these cells are abnormally sensitive to apoptosis in response to activation signals. Recent work has implicated downregulation of Bcl-2 with the increased spontaneous apoptosis in lymphocytes from HIV-infected patients. We have evaluated the roles of the apoptosis-protective proteins Bcl-2 and Bcl-x in stimulated PBMC from asymptomatic HIV-infected and HIV-uninfected individuals. We found that Bcl-2 was constitutively expressed in PBMC from both HIV-infected and uninfected samples. However, Bcl-x induction was delayed and responses were decreased in stimulated HIV-infected samples. Additionally, single-cell intracellular staining of Bcl-x revealed a significant inverse correlation between PWM-induced Bcl-x expression and apoptosis (r = −0.695, P = 0.005). This was confirmed at the single-cell level in direct experiments when stimulated cells were sorted based on Bcl-x induction and then measured for apoptosis. Furthermore, low Bcl-x expression was not due to reduced lymphocyte activation following PWM stimulation. Our data indicate that the induction of Bcl-x is markedly impaired in asymptomatic HIV-infected patients and that stimuli which induce inadequate expression of Bcl-x are associated with increased levels of apoptosis in these cells.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    Bioscience reports 17 (1997), S. 53-66 
    ISSN: 1573-4935
    Schlagwort(e): Superoxide ; nitrogen monoxide ; NO, peroxynitrite ; calcium ; membrane potential ; cytochrome oxidase ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The reduction of molecular oxygen to water provides most of the biologically useful energy. However, oxygen reduction is a mixed blessing because incompletely reduced oxygen species such as superoxide or peroxides are quite reactive and can, when out of control, cause damage. In mitochondria, where most of the oxygen utilized by eukaryotic cells is reduced, the dichotomy of oxygen shows itself best. Thus, reactive oxygen is a threat to them, as is evident from oxidative damage to mitochondrial lipids, proteins, and nucleic acids. Reactive oxygen, in the form of peroxides, also serves useful functions in mitochondria. This is exemplified by the control of mitochondrial and cellular calcium homeostasis, whose understanding has improved greatly during the last few years. An exciting new aspect is the discovery that nitric oxide and congeners have an enormous impact on mitochondria. Physiological concentrations of nitrogen monoxide (NO) at physiological cellular oxygen pressure inhibit cytochrome oxidase and thereby respiration. A transient inhibition of cytochrome oxidase by NO appears to be used in at least some forms of cell signalling. Peroxynitrite, the product of the reaction between superoxide and NO, can stimulate the specific calcium release pathway from mitochondria by oxidizing some vicinal thiols in mitochondria. There is evidence mounting that mitochondrial calcium handling and its modulation by reactive oxygen and nitrogen species is important for necrotic and apoptotic cell death.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    Bioscience reports 17 (1997), S. 347-366 
    ISSN: 1573-4935
    Schlagwort(e): Reactive oxygen species ; mitochondria ; pore ; apoptosis ; uncoupling ; non-coupled respiration ; aconitase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract New facts and ideas concerning the membrane-linked mechanisms preventing superoxide formation are summarised here. It is assumed that aerobic cells possess several lines of anti-ROS defence, including optimisation of the intracellular oxygen concentration, decrease in the concentration and life-time of one-electron O2 reductants such as CoQH; and mitochondrial and cell selections, i.e. elimination of mitochondria and cells producing ROS at high rate. It is postulated that ROS-dependent pore opening and ROS-dependent apoptosis are involved in mitochondrial and cell selections.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nuclear medicine 24 (1997), S. 1167-1170 
    ISSN: 1619-7089
    Schlagwort(e): Technetium-99m furifosmin ; radionuclide imaging ; breast cancer ; ovarian cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Recent in vitro studies suggest that technetium-99m furifosmin may have tumour-seeking properties. We analysed the diagnostic value of99mTc-furifosmin scintigraphy in nine patients with documented carcinoma of the breast and in eight patients with continued recurrent ovarian cancer. In the breast,99mTc-furifosmin failed to visualize the primary malignant tumour and the associated malignant lymph nodes in all patients. In contrast, multiple sites of increased tracer uptake were demonstrated in one patient with acute benign inflammatory breast disease. In four of eight patients with recurrent ovarian cancer,99mTc-furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased uptake corresponding to adhesions to the bowel as diagnosed by computed tomography, but failed to reveal further abnormalities in all patients. The present study demonstrates that furifosmin is of no value in the imaging of breast cancer and recurrent ovarian cancer. These results do not continue the pattern observed in cell culture studies and are quite in contrast to the findings of mammoscintigraphy using99mTc-methoxyisobutylisonitrile and99mTc-tetrofosmin.
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nuclear medicine 24 (1997), S. 1167-1170 
    ISSN: 1619-7089
    Schlagwort(e): Key words: Technetium-99m furifosmin ; radionuclide imaging ; breast cancer ; ovarian cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract. Recent in vitro studies suggest that technetium-99m furifosmin may have tumour-seeking properties. We analysed the diagnostic value of 99mTc-furifosmin scintigraphy in nine patients with documented carcinoma of the breast and in eight patients with continued recurrent ovarian cancer. In the breast, 99mTc-furifosmin failed to visualize the primary malignant tumour and the associated malignant lymph nodes in all patients. In contrast, multiple sites of increased tracer uptake were demonstrated in one patient with acute benign inflammatory breast disease. In four of eight patients with recurrent ovarian cancer, 99mTc-furifosmin scintigraphy demonstrated early (5 min p.i.) localized increased uptake corresponding to adhesions to the bowel as diagnosed by computed tomography, but failed to reveal further abnormalities in all patients. The present study demonstrates that furifosmin is of no value in the imaging of breast cancer and recurrent ovarian cancer. These results do not continue the pattern observed in cell culture studies and are quite in contrast to the findings of mammoscintigraphy using 99mTc-methoxyisobutylisonitrile and 99mTc-tetrofosmin.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    Cytotechnology 23 (1997), S. 231-239 
    ISSN: 1573-0778
    Schlagwort(e): apoptosis ; hybridoma ; amino acids ; starvation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract Two mouse hybridoma cell lines cultured in different basal media withthe iron-rich protein-free supplement were subjected to deliberatestarvation by inoculation into media diluted with saline to 50% or less.In the diluted media the growth was markedly suppressed and a largefraction of cells died by apoptosis. The cells could be rescued fromapoptotic death by individual additions of amino acids, such as glycine,L-alanine, L-serine, L-threonine, L-proline, L-asparagine, L-glutamine,L-histidine, D-serine, β-alanine or taurine. Amino acids withhydrophobic or charged side chains were without effect. The apoptosispreventing activity manifested itself even in extremely diluted media,down to 10% of the standard medium. The activity of L-alanine in theprotection of cells starving in 20% medium was shown also in semicontinuousculture. In the presence of 2 mM L-alanine the steady-state viable cell density more than doubled, with respect to control, andthe apoptotic index dropped from 37% in the control to 16%. It wasconcluded that the apoptosis-preventing amino acids acted as signalmolecules, rather than nutrients, and that the signal had a character ofa survival factor. The specificity of present results, obtained with twodifferent hybridomas, supports our view (Franěk and Chládková-Šrámková, 1995) that the membranetransport macromolecules themselves may play the role of therecognition elements in a signal transduction pathway controlling thesurvival of hybridoma cells.
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  • 39
    ISSN: 1573-0778
    Schlagwort(e): apoptosis ; bcl-2 ; COS cell ; myeloma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract COS, myeloma and HeLa cells, which are commonly used for protein production by cell culture, were transfected with human bcl-2 gene encoded on the shuttle vector BCMGS. Expression of human bcl-2 improved survival of cells remarkably, mildly, or negligibly for COS, myeloma, and HeLa, respectively. Four clones were obtained from the human bcl-2 expressing cell population of COS cells. They expressed human bcl-2 almost at the same level. The viable cell numbers were 6, 2.5, 2.5, and 0.8 times as many for the clones #8, #5, #6, and #7, respectively, as for the control COS cells, when they were cultured at low (0.2%) serum concentration for 9 days. The bcl-2 overexpressing COS cells showed morphology different from that of the control COS cells in serum limited condition. When transfected with mouse lambda protein gene carried by an SV40-derived vector, clone #8 of the bcl-2 transfected COS cells continued the transient expression of lambda protein longer than the control COS cells.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    Cytotechnology 25 (1997), S. 127-135 
    ISSN: 1573-0778
    Schlagwort(e): apoptosis ; CD8+T cell ; cell death ; concanamycin A
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract Concanamycin A (CMA) and concanamycin B (CMB) are specific inhibitors of vacuolar type H+-ATPase (V-ATPase). In our previous studies, intraperitoneal injection of CMB was shown to suppress the increase in CD8+ CTL population, but not to affect CD4+ and B220+ populations, in mice immunized with allogeneic tumors. To clarify the molecular basis of the selective decrease in the CD8+ CTL population by CMB, we have performed a series of in vitro experiments with use of CMA. Cell viability of the CD8+ population prepared from the immunized mice was preferentially decreased by CMA treatment. Moreover, in the CD8+ CTL clone, CMA induced a marked DNA fragmentation and nuclear condensation characteristic of apoptosis. Anti-CD3 or phorbol ester accelerated the CMA-induced reduction in cell viability of the CD8+ CTL clone, but not CD4+ T cell clones. However, this rapid cell death was not accompanied by DNA fragmentation and nuclear condensation. Perforin and granzyme B were unlikely to be involved in such cell death. Thus, our data suggest that V-ATPase activity is essential for survival of CD8+ CTL especially when activated.
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  • 41
    ISSN: 1573-0778
    Schlagwort(e): apoptosis ; programmed cell death ; nucleotides ; energy charge ; CHO cells ; batch culture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin , Werkstoffwissenschaften, Fertigungsverfahren, Fertigung
    Notizen: Abstract Temperature reduction in CHO cell batch culture may be beneficial in the production of recombinant protein and in maintenance of viability. The effects on cell cycle, apoptosis and nucleotide pools were studied in cultures initiated at 37°C and temperature shifted to 30 °C after 48 hours. In control cultures maintained at 37 °C, viable cells continued to proliferate until the termination of the culture, however, temperature reduction caused a rapid decrease in the percent of cells in S phase and accumulation of cells in G-1. This was accompanied by a concurrent reduction in U ratio (UTO/UDP-GNAc), previously shown to be a sensitive indicator of growth rate. Culture viability was extended following temperature shift, as a result of delayed onset of apoptosis, however, once initiated, the rate and manner of cell death was similar to that observed at 37 °C. All nucleotide pools were similarly degraded at the time of apoptotic cell death. Temperature reduction to 30 °C did not decrease the energy charge of the cells, however, the overall rate of metabolism was reduced. The latter may be sufficient to extend culture viability via a reduction in toxic metabolites and/or limitation of nutrient deprivation. However, the possibility remains that the benefits of temperature reduction in terms of both viability and productivity are more directly associated with cultures spending extended time in G-1.
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  • 42
    ISSN: 1573-7276
    Schlagwort(e): annexin ; breast cancer ; calcium-binding protein ; cell surface ; immunohistochemistry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Annexins are a family of structurally related, water-soluble proteins that have calcium- and phospholipid-binding domains. Annexin I is thought to be involved in cell proliferation and differentiation and has recently been shown to be expressed on the surfaces of lymphoma cells where it acts as an endothelial cell adhesion molecule. To evaluate the expression of annexin I in relation to human breast cancer development and progression we used breast biopsy tissues. Immunohistochemical analysis of annexin I in paraffin-embedded ductal epithelial cells of various human breast tissues indicated that this annexin was not demonstrable in the ductal luminal cells of normal breast tissues (n = 11) and benign tumors (n = 10) (except for one ductal adenoma) but was generally expressed in various types of breast cancers, including noninvasive ductal carcinoma in situ (DCIS), invasive and metastatic breast tumors (n = 33). The results suggest that annexin I expression might correlate with malignant breast cancer progression but it is most likely involved at an early stage of human breast cancer development.
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  • 43
    ISSN: 1573-7373
    Schlagwort(e): neuroblastoma ; differentiation ; programmed cell death ; apoptosis ; transfection ; NGFR ; TrkA ; TrkB ; TrkC ; NGF ; BDNF ; NT-3 ; N-myc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors of the peripheral nervous system. Evidence from several independent studies suggests that high expression of TrkA is an indicator of favorable outcome, and there is an inverse correlation between TrkA expression and N-myc amplification. In addition, some primary neuroblastomas differentiate in vitro in the presence of NGF but die in its absence. We have evidence that coexpression of full-length TrkB and BDNF is associated with N-myc amplification and may represent an autocrine survival pathway. Conversely, truncated TrkB is expressed predominantly in differentiated tumors. Finally, TrkC is expressed in favorable neuroblastomas, essentially all of which also express TrkA. In summary, the study of neurotrophin receptor expression and function in neuroblastomas may provide important insights into the role that these pathways play in the pathogenesis and clinical behavior of this tumor. Ultimately, these pathways may provide attractive targets for the development of therapy aimed at inducing differentiation or programmed cell death in these tumors.
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  • 44
    ISSN: 1573-7373
    Schlagwort(e): neuroblastoma ; retinoic acid ; NRII convertase ; aminopeptidase-β ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Under retinoic acid exposure, the three SK-N-BE(2)-derived human neuroblastoma cell lines, BE(2)-NA, BE(2)-SA and BE(2)-M17 undergo mainly differentiation, apoptosis or continue to proliferate, respectively. We have used this model system to study the modulation of the transcriptional expression of putative processing enzymes, two novel metallopeptidases; i.e. N-arginine dibasic convertase (NRD convertase; EC 3.4.24.61) and an aminopeptidase-B after exposure of the cells either to retinoic acid or to synthetic retinoid analogs. The data indicate that the two respective enzymes are differently modulated in the various cell lines. Whereas aminopeptidase-B expression is enhanced in most cases, NRD convertase appears to undergo opposite regulation in proliferating versus differentiating neuroblastoma cells. It is concluded that both genes might contain retinoic acid regulatory elements (RARE) in their promoters.
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neuro-oncology 35 (1997), S. 161-167 
    ISSN: 1573-7373
    Schlagwort(e): brain metastasis ; breast cancer ; surgery ; radiotherapy ; chemotherapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Twenty-eight consecutive patients with breast cancer were analyzedwho presented with a single brain metastasis asfirst site of distant metastasis. The response tosurgery with postoperative radiation therapy (RT) (9 patients)and to non-surgical therapy as first-line treatment was100% and 89% respectively with a significant differencein median recurrence-free intervals of 23 months andof 5 months respectively (p=0.033). Retreatmentof a local relapse by surgery (± RT,± chemotherapy) or by non-surgical treatment resulted ina response in 6 of the 7 operatedpatients and in 5 of the 6 non-operatedpatients with a median duration of response of7 months (range 2–20 months) and of 3months (range 2–4 months) respectively. The overall mediansurvival of the 28 patients with a singlebrain metastasis was 16 months (range 2–39 months).The median survival in the primarily operated patientswas 23 months, in the primarily not-operated group10 months, and in the never-operated group 9months. In comparison, the response to non-surgical treatmentin 20 consecutive patients who presented with multiplebrain metastases as first site of distant metastasiswas 55% with a median recurrence free intervalof 4 months. The median survival in thisgroup was 4 months, which was significantly shorterthan survival of patients with single brain metastasis(p=0.0036). These results suggest that breastcancer patients with a single brain metastasis asfirst presentation of relapse constitute a specific subgroupwith a favorable response to treatment and along survival especially if they can be treatedby surgery with postoperative RT.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neuro-oncology 31 (1997), S. 33-39 
    ISSN: 1573-7373
    Schlagwort(e): neuroblastoma ; N-myc ; cisplatin ; VP-16 ; radiation ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract N-myc amplification correlates with poor prognosis in neuroblastoma patients. Although the reason for this is unclear, it is possible that amplified N-myc confers resistance to certain agents used in the therapy of the disease. The acquisition of resistance to cytotoxic drugs in human tumour cells is multifactorial. One mechanism involved in the development of drug resistance is an increased efficiency of DNA repair. This could reduce the effectiveness of both cisplatin and etoposide (VP-16). Previous studies on human neuroblastoma cells have shown a relationship between N-myc copy number and cisplatin sensitivity [1]. We now report the response to VP-16 treatment of five human neuroblastoma cell lines with a range of N-myc gene copy numbers. After exposure of cells to drug for 24 hours, survival curves were constructed from clonogenic assay data and the iso-effective dose (the dose required to produce 1 log cell kill) was derived. The relationship between N-myc copy number or expression and response to VP-16 was assessed. A significant correlation was established between VP-16 resistance and copy number (r = 0.82; P 〈 0.05). However, no association was found between N-myc expression and isoeffective dose of VP-16. These results indicate that N-myc amplification may be responsible for treatment failure in those patients receiving cisplatin or VP-16.
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neuro-oncology 31 (1997), S. 65-83 
    ISSN: 1573-7373
    Schlagwort(e): neuroblastoma ; retinoic acid ; programmed cell death ; apoptosis ; transglutaminase ; trk
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Cell proliferation, the balance between mitosis and apoptosis is the result of the continuous integration of a number of different signal transduction pathways stimulated in a cell at any given point in its life. Neuroblastoma cells regulate the switch between mitosis and death, according both to intrinsic factors and extrinsic factors, such as growth factor withdrawal and action of the vitamin A derivative, retinoic acid. In this review, we describe the balance of some factors regulating growth and death of human neuroblastoma cells in vitro. These dynamic studies are necessarily performed on cell lines, which offer controlled conditions enabling the disection of the complex stimuli mediating survival and growth (IGF, trk, BDNF) and death (transglutaminase, free radicals, Bcl-2). Although the conclusions drawn may therefore not be directly applicable to tumour cells in vivo, the results herein discussed are of sufficient significance to warrant in vivo relevance.
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  • 48
    ISSN: 1573-7373
    Schlagwort(e): anticancer drugs ; cell cycle ; apoptosis ; hamster fibrosarcoma
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The induction of apoptosis by anticancer drugs and its relationship to stages of the cell cycle was studied in cells derived from a solid tumour; a highly malignant hamster fibrosarcoma (Met B). Asynchronously proliferating cells were treated with a wide variety of agents such as actinomycin-D, 1-β-D-arabinofuranosyl cytosine, camptothecin, cisplatin, cyclophosphamide, daunorubicin, 5-flurouracil, 6-mercaptopurine, hydroxyurea, ionomycin, methotrexate and vincristine. With the exception of cyclophosphamide and hydroxyurea, a 36 h exposure to these drugs resulted in inhibition of cell growth and apart from cyclophosphamide, hydroxyurea, 6-mercaptopurine and cisplatin the induction of apoptosis. Studies using a decreased concentration of drug and exp osure time (12 h) followed by examination of cells using flow cytometry indicated that most drugs were capable of affecting cell cycle progression without induction of apoptosis. However when cells were synchronised at G0/G1, S and G2/M phases and then exposed to these decreased concentrations of drug apart from 6MP an HU, apoptosis was observed and for the majority of drugs it took place in the same phase in which progression through the cell cycle was blocked by the drug. Cells synchronised in G0/G1 phase were more susceptible to methotrexate, whereas S-phase cells were more susceptible to camptothecin and 5-flurouracil and G2/M phase cells more susceptible to actinomycin D, 1-β-D-arabinofuranosyl cytosine, daunorubicin and cisplatin. In contrast, vincristine blocked cells in G2/M phase but exerted its apoptotic effect in S-phase cells, ionomycin had no effect on the cell cycle, but G2/M cells appeared to be more susceptible to the effect of this drug. These data indicate that entry into apoptosis by this fibrosarcoma may occur at any point in the cell cycle. They also demonstrate a correlation between the action of some anticancer drugs on the cell cycle and the subsequent induction of apoptosis which may be useful in chemotherapeutic design.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neuro-oncology 31 (1997), S. 209-215 
    ISSN: 1573-7373
    Schlagwort(e): apoptosis ; neuroblastoma ; N-myc ; DNA fragmentation ; Terminal deoxynucleotidyl Transferase ; flow cytometry
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neuroblastoma (NB) is a tumor of pediatric age that is associated with high mortality in metastatic stages, although stage IVS patients undergo frequent spontaneous regression. Since apoptosis has been proposed as a possible cause of remission among cancer patients, we tested this hypothesis among both localized and metastatic NB and, in particular, NB metastatic stage IVS. We have assayed 36 localized and 117 metastatic neuroblastomas for evidence of internucleosomal DNA degradation and confirmed DNA fragmentation by the flow cytometric Terminal deoxynucleotidyl Transferase method, which also allowed us to measure DNA content and cell cycle phases. These techniques provided evidence of apoptosis in 18 out of 153 samples (11.8%), that were equally distributed among all stages except IVS, i.e., 11.1% in stage I (2/18), 11.1% in stage II (2/18), 13.2% in stage III (5/38), 13.4% in stage IV (9/67), and 0% in stage IVS (0/12). Tumor tissue samples collected at ons et and also at relapse for the same patients showed that apoptosis may occur at relapse. In addition, cells appear to undergo apoptosis independently from N-myc amplification, cell cycle phase and DNA ploidy. In conclusion, apoptosis seems to take place with about an equal frequency for both favourable and unfavourable stages with an exception for IVS. Since DNA fragmentation remained undetected in stage IVS, we suggest that apoptosis is not a mechanism of spontaneous regression for these patients. A better basic understanding of the complex molecular mechanisms and biochemical pathways that control apoptosis in neuroblastoma appears to be necessary.
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neuro-oncology 35 (1997), S. 55-64 
    ISSN: 1573-7373
    Schlagwort(e): breast cancer ; carainomatous meningitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose. To identify the factors predictive of response and increasedsurvival in patients with leptomeningeal metastases (LM) from breast cancerreceiving multi-modal therapy. Background. Leptomeningeal metastases (LM)are being diagnosed with increasing frequency as anti-cancer therapiesbecome more effective and result in prolonged patient survival. Patients andmethods. 32 women (range 28 to 74 years; median 49) with LM due tometastatic breast cancer were treated. Neurologic presentation included:cranial neuropathies (10 patients); headache (10); cauda equina syndrome(6); ataxia (6); meningismus (3); radioculopathy (2); myelopathy (2);confusion (2); and seizure (1). All patients underwent radiographicevaluation of the extent of CNS disease followed by radiotherapy (21 women)and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22;thio-TEPA 11). Results. CNS imaging (cranial MR, spine MR and radionuclideventriculography) demonstrated: interrupted CSF flow (21); subarachnoidnodules (8); parenchymal brain metastases (6); hydrocephalus (4); andepidural spinal cord compression (1). Cytologic responses were seen in 14women to first-, 7 to second- and 3 to third-line chemotherapy.Treatment-related toxicity included 21 women with aseptic meningitis and 10women with thrombocytopenia or neutropenia (5 related to intraventricularchemotherapy). Median survival was 7.5 months (range 1.5 to 16). 18 womendied of progressive LM or combined LM and systemic disease progression.Women with persistent interruption of CSF flow fared worse than women withnormal CSF flow (median survival 3 versus 10 months; p 〈 0.0001).Conclusion. LM in women with metastatic breast cancer may be palliated withcombined modality therapy, however, success of therapy and survival is basedupon pre-treatment CNS extent of disease evaluation.
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  • 51
    ISSN: 1573-7373
    Schlagwort(e): apoptosis ; glioma ; anti-Fas antibody ; liposome
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We investigated the susceptibility of five human glioma cell lines toanti-Fas antibody. All human glioma cells tested constitutively expressedFas antigen on their surfaces and the level of the expression variedslightly in each cell line. The cells had a low susceptibility to anti-Fasantibody-mediated apoptosis. There were four moderately resistant cell lines(U251-SP, U251-MG, SK-MG-1, T98) and one highly resistant cell line (U251nu/nu). For this study we prepared liposomes containing anti-Fas antibodyand studied the augmentation of the antibody-mediated apoptosis. Theliposomes induced apoptosis significantly more often than did anti-Fasantibody alone. These results indicate that anti-Fas antibody-mediatedapoptosis does not require a critical level of cell surface expression ofFas antigen but rather depends on the intensity of Fas signal transduction.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    International journal of sexuality and gender studies 2 (1997), S. 101-121 
    ISSN: 1573-8167
    Schlagwort(e): femininity ; breast cancer ; lesbian identity ; health care ; homophobia ; heterosexism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Sociologie
    Notizen: Abstract The author discusses writings by Eve Kosofsky Sedgwick, Kathleen Martindale, Audre Lorde, and Barbara Rosenblum on their experiences with breast cancer, and explores their articulations of the impact mastectomy has had on their sense of “femininity” in relation to their own identities and body images, and in relation to cultural expectations, and how others perceive them. Their identification of the body as socially produced, and as a site of contestation and multiple struggles, offers a strategic site from which to engage with the violent gender-inflected notion of the “ideal” female body. Themes addressed include: the process of writing embodied experience to make it real, the body's role in the process of identity formation, the culturally constructed significance of appearance to the individual's sense of “femininity,” the value of the female body in a capitalistic society, and heterosexism in society and in the health care system.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    Cancer causes & control 8 (1997), S. 93-108 
    ISSN: 1573-7225
    Schlagwort(e): Abortion ; breast cancer ; pregnancy ; women
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To evaluate the relationship between breast cancer risk and spontaneous and induced abortion, we conducted a detailed descriptive review of 32 epidemiologic studies that provided data by type of abortion and by various measures of exposure to abortion-number of abortions, timing of abortion in relation to first full-term pregnancy, length of gestation, and age at first abortion. Breast cancer risk did not appear to be associated with an increasing number of spontaneous or induced abortions. Our review also suggested that breast cancer risk probably was not related to the other measures of exposure to abortion, and probably did not differ by age or a family history of breast cancer. Finally, the data appeared to suggest a slightly increased risk among nulliparous women, but this tendency was based primarily on studies with a small number of nulliparous women who had had spontaneous or induced abortions. Definitive conclusions about an association between breast cancer risk and spontaneous or induced abortion are not possible at present because of inconsistent findings across studies. Future investigations should consider prospective designs, separate analyses of spontaneous and induced abortions, appropriate referent groups, and adequate adjustment for confounding and effect modification. Future investigations also should attempt to determine whether any increased risks reflect the transient increase in breast cancer risk hypothesized for full-term pregnancy or a causal relationship specific to spontaneous or induced abortion.
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  • 54
    ISSN: 1573-675X
    Schlagwort(e): AKR lymphoma ; apoptosis ; cell proliferative capacity ; metastatic potential
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The possibility that apoptosis and/or cell proliferation have a role in tumour progression in a murine T cell lymphoma was tested. The model consisted of the comparison of primary (PT) and metastatic tumour (MT) cells. The PT cells, but not the MT cells displayed a very pronounced tendency for spontaneous apoptosis. Proliferative capacity of MT cells was lower than that of PT cells, suggesting that it does not contribute to the metastatic phenotype in this system. Release from apoptosis does however, probably, play a role in the aggressiveness of the lymphoma.
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  • 55
    ISSN: 1573-675X
    Schlagwort(e): Adriamycin (ADM) ; apoptosis ; Bax ; Bcl-2 ; p21WAF1/CIP1 ; p53 ; Transitional Cell Cancer (TCC)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Genotoxic stimuli, including anticancer drugs, induce apoptosis in cancer cells through increase of p53, p21WAF1/CIP1 , at least in part. Bcl-2 and Bax modify this pathway or directly regulated by p53. Here we studied Adriamycin (ADM)-induced apoptosis in four human bladder cancer cell lines in respect of p53, p21WAF1/CIP1 and Bcl-2 family proteins. After ADM, treatment bladder cancer cells underwent dose-dependent cell death with typical morphologic features of apoptosis. Among four cell lines RT4 with wt p53, low ratio of Bcl-2 to Bax and induction of p21WAF1/CIP1 after ADM treatment, was the most sensitive to induction of apoptosis. Thus, p53, p21WAF1/CIP1 , Bcl-2 and Bax status might determine susceptibility of bladder cancer cells to ADM induced apoptosis.
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  • 56
    ISSN: 1573-675X
    Schlagwort(e): 2-acetylaminofluorene (2-AAF) ; apoptosis ; aromatic amines ; cell proliferation ; complete carcinogens ; tumour promotion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract To investigate effects that distinguish AAF from incomplete carcinogens, the rate of cell death (apoptosis) and cell proliferation was studied at early stages of AAF induced rat liver carcinogenesis. Male Wistar rats were fed 0.04% AAF in the diet for 2, 6 and 16 weeks and immunohistochemical markers were measured in the liver. The formation of initiated cells and preneoplastic foci was followed by staining for GST-P (glutathione-S-transferase). GST-P-positive foci were present from 6 weeks on. Apoptosis was increased in the periportal area and in preneoplastic foci at all time points. Cell proliferation was enhanced in the periportal area in oval cells and in bile duct-like cells particularly at 2 and 6 weeks and mainly in GST-P positive foci at 16 weeks. Notably, more cells always proliferated than were eliminated. Other apoptosis-related markers like p53 and FAS/Apo-1 could not be demonstrated in either normal hepatocytes, preneoplastic foci or in hepatocytes from treated animals. Scattered bcl-2 positive cells were present in livers at 16 weeks of treatment. The two cell growth and differentiation related proto-oncogenes c-FOS and c-JUN were increased in all treated animals at early stages. If feeding was stopped after 6 weeks, livers did not recover significantly within the following 10 weeks. The results support the complex effects of AAF in rat liver carcinogenesis. Chronic toxicity locally impairs the balance between cell proliferation and cell death and induces morphological alterations that promote the growth of initiated cells.
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  • 57
    ISSN: 1573-675X
    Schlagwort(e): 5-FU ; apoptosis ; bax ; gastric cancer ; p53 ; p21/waf1
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract We examined chemosensitivity to 5-fluorouracil (5-FU) in four human gastric cancer cell lines, by analyzing the expression of p53 and its related genes. Treatment with 1mM 5-FU induced variable degrees of apoptosis in the cultured cells. The apoptotic indices 72 h after treatment were approximately 14% in MKN-74 (wild-type p53 gene), 12% in MKN-45 (wild-type), 3% in MKN-28 (mutated) and 0.5% in KATO-III cells (deleted), respectively. On the other hand, 50 μM 5-FU had little effect on the induction of apoptosis in MKN-74 cells, the value being approximately 2% after 72 h. Induction of P53 expression was noted 3 h after initiating the treatment, followed by the induction of P21/Waf1 after 6 h in both MKN-74 and MKN-45 cells. The same expression mode was noted in MKN-74 treated with 50 μM 5-FU. Conversely, the level of P53 expression was constant in MKN-28 cells and absent in KATO-III cells, in which P21/Waf1 had never been induced. The Bax/Bcl-2 expression ratio was gradually elevated for up to 72 h in MKN-74 and MKN-45 cells treated with 1mM 5-FU; in contrast, it was unchanged in MKN-28 and KATO-III cells, and MKN-74 treated with 50 μM 5-FU. These results might indicate that (1) 1mM 5-FU induces apoptosis in cultured gastric cancer cells carrying the wild-type p53 gene, but not those carrying the mutated type or a gene deletion, and (2) the elevated Bax/Bcl-2 expression ratio plays a more crucial role than the higher expression of P21/Waf1 in the induction of p53- gene dependent apoptosis.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    Apoptosis 2 (1997), S. 257-264 
    ISSN: 1573-675X
    Schlagwort(e): Antioxidant enzymes ; apoptosis ; Bcl-2 ; free radicals ; NF-kB ; protein synthesis ; transcription factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Cycloheximide (CHX), long recognized for its ability to inhibit protein synthesis, has been widely employed in studies of cell death to the extent that prevention of cell death by CHX has been used as prima facie evidence for a subtype of apoptosis called ‘programmed cell death’. However, very rarely have investigators determined the effects of CHX on protein synthesis in their particular cell death paradigms. Recent findings are revealing alternative mechanisms of action of CHX that involve, ironically, stimulation of cytoprotective signalling pathways. For example, in embryonic rat hippocampal cell cultures CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including Bcl-2. CHX induces increases in immediate early gene mRNA levels, and can activate several different kinases and transcription factors that are also activated by various insults and in response to anti-apoptotic growth factors. Concentrations of CHX that cause only a modest and/or transient decrease in over-all protein synthesis may prevent cell death by inducing cytoprotective signalling pathways (‘programmed cell life’), whereas higher concentrations of CHX may prevent cell death by blocking the expression of ‘death genes’. Establishing which of these anti-apoptotic mechanisms of action of CHX is operative in each cell death paradigm is clearly essential for proper interpretation of experimental results.
    Materialart: Digitale Medien
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  • 59
    ISSN: 1573-675X
    Schlagwort(e): Ameloblasts ; apoptosis ; electronmicroscopy ; insulin-like growth factor ; odontogenesis ; rat incisor
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Insulin-like growth factor-I (IGF-I) is a pleiotrophic polypeptide which appears to have roles both as a circulating endocrine hormone and as a locally synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in regulating the growth of cells in vivo and in vitro and initiates metabolic and mitogenic processes in a wide variety of cell types by binding to specific type I receptors in the plasma membrane. In this study, we report the distribution of IGF-I receptors in odontogenic cells at the ultrastructural level using the high resolution protein A-gold technique. In the pre-secretory stage, very little gold label was visible over the ameloblasts and odontoblasts. During the secretory stage the label was mostly seen in association with the cell membranes and endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post-secretory stage were labelled as well as multivesicular dense bodies. Very little labelling was encountered in the ameloblasts in the transitional stage, where apoptotic bodies were clearly visible. The maturation stage also exhibited labelling of the secretory-like granules in the distal surface. The presence of gold particles over the plasma membrane is an indication that IGF-I receptor is a membrane-bound receptor. Furthermore, the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF-I receptor. The absence of labelling over the transitional ameloblasts suggests that the transitional stage may require the non-expression of IGF-I as a prerequiste or even a trigger for apoptosis.
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  • 60
    ISSN: 1573-675X
    Schlagwort(e): AAPH ; apoptosis ; Bcl-2 ; free radicals ; leukaemic cells ; oxidative stress
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The aim of this study was to explore the dose- and time-dependent effects of hydrophilic peroxyl radical initiator 2,2'azobis(2amidinopropane)dihydrochloride (AAPH) on apoptosis, and on expression of Bcl-2 in L1210 leukaemic cells. We observed a progressive increase of intracellular concentration of oxygen free radicals (OFR), manifested by the rise of 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, di(acetoxymethyl ester) oxidation, during 24 h of cells exposure to AAPH. Oxidative stress was associated with peroxidation of cellular lipids, which was demonstrated by the measurement of thiobarbituric acid-reactive substances and conjugated dienes. Analysis of cell viability by the use of trypan blue exclusion method revealed that AAPH reduced the ability of L1210 cells to multiply or survive. AAPH increased the number of leukaemic cells with typical features of apoptosis like condensation of chromatin, pyknosis and fragmentation of nucleus, followed by secondary necrosis. A characteristic internucleosomal DNA cleavage, visualized as a DNA ‘ladder’ consisting of fragments that are multiples of 180-200 bp was also observed. The intensity of apoptosis was dependent on AAPH concentration, time of cell exposure and the availability of growth factors and nutrients in extracellular environment (FCS concentration). The novel observation is the increase of Bcl-2 level in L1210 leukaemic cells surviving an oxidative stress. The level of Bcl-2 protein significantly rose with increasing AAPH concentration, and time of cell exposure to this oxidant. This phenomenon could be the result of: (1) negative selection of cells with the lowest expression of bcl-2, being more susceptible to oxidative stress and (2) increased synthesis and/or decreased degradation of Bcl-2 protein as an adaptation to continuous OFR loading. In contrast to growth-promoting medium (10% FCS/RPMI), the maintenance medium (2% FCS/RPMI) did not cover cell requirements for progressive Bcl-2 increase at the highest AAPH concentration (2 mM) applied in this study. Several observations indicate that the increased Bcl-2 level in surviving L1210 leukaemic cells exposed to oxidative stress is a symptom of their natural defence against cellular lipids peroxidation and apoptosis.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    Apoptosis 2 (1997), S. 319-329 
    ISSN: 1573-675X
    Schlagwort(e): Acute myeloblastic leukaemia ; all-trans retinoic acid ; apoptosis ; differentiation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract The effect of all-trans retinoic acid (ATRA) on leukaemia cell differentiation, proliferation and induction of apoptosis was studied by using autonomously growing blast cells isolated from eight patients with acute myeloblastic leukaemia (AML) either at diagnosis ( n=4) or at relapse (n=4). No morphological or functional differentiation induced by ATRA was observed in any of the cases studied. In cell cultures, inhibition of leukaemia cell growth by ATRA was obvious, especially in the case of clonogenic cells, and it was both time- and concentration-dependent. Induction of apoptosis was more difficult to achieve. The cells retained over 90% viability in suspension when the ATRA exposure at any of the concentrations studied was 48 h or less. When the time of exposure to ATRA was longer than 48 h, the viability of the cells decreased in a concentration-dependent manner. Apoptosis was observed morphologically in each of the AML cases with 10-5 to 10-8 M ATRA, if the incubation time of cells in ATRA was 72 h. The percentage of apoptotic cells increased with increasing ATRA concentrations from 12± 9% of 10-8 M ATRA to 78±12% of 10-5 M ATRA. The DNA electrophoretic method was able to detect apoptosis in all the AML samples exposed to 10-7 and 10-6 ATRA for 48 h and occasionally in cases where lower concentrations and longer exposure time were used. In conclusion, the present study shows that it is possible to induce apoptotic leukaemia cell death in vitro with ATRA in AML, and this effect is dependent on both concentration and exposure time.
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  • 62
    ISSN: 1573-675X
    Schlagwort(e): Acute lymphoblastic leukaemia ; apoptosis ; bcl-2 ; Fas
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Seventy-two samples with initial and 23 samples with relapsed childhood acute lymphoblastic leukaemia (ALL) were investigated for apoptotic index (AI) and for Fas expression. AI was determined by DNA-fragmentation using deoxynucleotidyl terminal transferase and Fas expression by immunocytochemistry. bcl-2 mRNA expression was measured in 50 initial and 20 relapsed ALL. The patients were discriminated in groups with low and high AI, Fas-protein expression and bcl-2mRNA expression by the mean value. AI was higher in relapsed than in initial ALL. The mean survival was significantly higher in patients with low AI ( p= 0.034). This was also true for the relapse-free interval, however, this result was borderline significant ( p= 0.064). AI was directly correlated with expression of Fas and inversely correlated with bcl-2 mRNA expression. These results suggest that Fas and - with limitations - bcl-2 may influence the apoptotic process in childhood ALL and that enhanced apoptotic activity predicts poor prognosis.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    Bioscience reports 17 (1997), S. 293-302 
    ISSN: 1573-4935
    Schlagwort(e): Mitochondria ; permeability transition pore ; dithiols ; glutathione ; pyridine nucleotides ; oxidative stress ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract The recent data on redox regulation of the mitochondrial cyclosporin-sensitive pore are reviewed here. They indicate that the pore is modulated by the redox state of pyridine nucleotides and glutathione at two independent sites. Special attention is paid to experimental approaches for studying this phenomenon in isolated mitochondria. The relation between oxidative stress and the opening of the mitochondrial pore in some cases of cell injury and in programmed cell death (apoptosis) is discussed.
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  • 64
    ISSN: 1573-4935
    Schlagwort(e): Mitochondria ; apoptosis ; oxygen radicals ; benzodiazepine receptor ; mitochondrial ; redox state ; cellular ; permeability transitions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract This review explores the alternative functions of mitochondria inside the cell. In a general picture of mitochondrial functioning, the importance and uniqueness of these intrinsic functions make them irreplaceable by other intracellular compartments. Among these are, participation in apoptosis and cellular proliferation, regulation of the cellular redox state and level of second messengers, heme and steroid syntheses, production and transmission of a transmembrane potential, detoxication and heat production. In most of the listed functions, reactive oxygen species modulate a number of non-destructive cellular activities. Some of the mitochondrial functions are reviewed in detail.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 14 (1997), S. 1659-1671 
    ISSN: 1573-904X
    Schlagwort(e): apoptosis ; programmed cell death ; drug induced apoptosis ; pharmacodynamic endpoint
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
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  • 66
    ISSN: 1573-6881
    Schlagwort(e): HL-60 ; ρ°HL-60 ; ubiquinone ; plasma membrane ; apoptosis ; ceramide
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Physik
    Notizen: Abstract Serum provides cultured cells with survival factors required to maintain growth. Its withdrawal induces the development of programmed cell death. HL-60 cells were sensitive to serum removal, and an increase of lipid peroxidation and apoptosis was observed. Long-term treatment with ethidium bromide induced the mitochondria-deficient ρ°HL-60 cell line. These cells were surprisingly more resistant to serum removal, displaying fewer apoptotic cells and lower lipid peroxidation. HL-60 cells contained less ubiquinone at the plasma membrane than ρ°HL-60 cells. Both cell types increased plasma membrane ubiquinone in response to serum removal, although this increase was much higher in ρ° cells. Addition of ubiquinone to both cell cultures in the absence of serum improved cell survival with decreasing lipid peroxidation and apoptosis. Ceramide was accumulated after serum removal in HL-60 but not in ρ°HL-60 cells, and exogenous ubiquinone reduced this accumulation. These results demonstrate a relationship between ubiquinone levels in the plasma membrane and the induction of serum withdrawal induced apoptosis, and ceramide accumulation. Thus, ubiquinone, which is a central component of the plasma membrane electron transport system, can represent a first level of protection against oxidative damage caused by serum withdrawal.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    Journal of medical systems 21 (1997), S. 303-307 
    ISSN: 1573-689X
    Schlagwort(e): automated mammography system ; breast cancer ; Computer Aided Diagnostic tool
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Automated processing of mammograms has been studied for several years. Until the last few years much of the efforts have produced marginal results due to the limitations of inexpensive hardware. Even with the advanced hardware no one has yet taken an entire mammogram and determined whether it is normal or abnormal. We outline a method here to attempt to do just that.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    Journal of bioenergetics and biomembranes 29 (1997), S. 315-330 
    ISSN: 1573-6881
    Schlagwort(e): Glycolysis ; pyruvate kinase type M2 ; glutaminolysis ; hydrogen shuttles ; phosphometabolites ; AMP ; NADH ; NADPH ; apoptosis ; tumor therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Physik
    Notizen: Abstract A common characteristic of tumor cells is the constant overexpression of glycolytic and glutaminolytic enzymes. In tumor cells the hyperactive hexokinase and the partly inactive pyruvate kinase lead to an expansion of all phosphometabolites from glucose 6-phosphate to phosphoenolpyruvate. In addition to the glycolytic phosphometabolites, synthesis of their metabolic derivatives such as P-ribose-PP, NADH, NADPH, UTP, CTP, and UDP-N-acetyl glucosamine is also enhanced during cell proliferation. Another phosphometabolite derived from P-ribose-PP, AMP, inhibits cell proliferation. The accumulation of AMP inhibits both P-ribose-PP-synthetase and the increase in concentration of phosphometabolites derived from P-ribose-PP. In cells with low glycerol 3-phosphate and malate-aspartate shuttle capacities the inhibition of the lactate dehydrogenase by low NADH levels leads to an inhibition of glycolytic ATP production. Several tumor-therapeutic drugs reduce NAD and NADH levels, thereby inhibiting glycolytic energy production. The role of AMP, NADH, and NADPH levels in the success of chemotherapeutic treatment is discussed.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    Journal of bioenergetics and biomembranes 29 (1997), S. 345-354 
    ISSN: 1573-6881
    Schlagwort(e): c-myc ; oncogene ; transcription ; hypoxia ; HIF-1 ; tumor metabolism ; glycolysis ; tumori-genesis ; apoptosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Physik
    Notizen: Abstract The ability of cancer cells to overproduce lactic acid aerobically was recognized by Warburg about seven decades ago, although its molecular basis has been elusive. Increases in glucose transport and hexokinase activity in cancer cells appear to account for the increased flux of glucose through the cancer cells. Herein we review current findings indicating that the c-Myc oncogenic transcription factor and hypoxia-inducible factor 1 (HIF-1) are able to bind the lactate dehydrogenase A promoter cis acting elements, which resemble the core carbohydrate response element (ChoRE), CACGTG. These and other observations suggest that the normal cell responds physiologically to changes in oxygen tension or the availability of glucose by altering glycolysis through the ChoRE, which hypothetically binds c-Myc, HIF-1, or related factors. The neoplastic cell is hypothesized to augment glycolysis by activation of ChoRE/ HIF-1 sites through direct interaction with c-Myc or through activation of HIF-1 or HIF-1 -like activity. We hypothesize that oncogene products either stimulate HIF-1 and related factors or, in the case of c-Myc, directly activate hypoxia/glucose responsive elements in glycolytic enzyme genes to increase the ability of cancer cells to undergo aerobic glycolysis.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    Neurochemical research 22 (1997), S. 517-521 
    ISSN: 1573-6903
    Schlagwort(e): Adaptation ; apoptosis ; hypoxia ; oxygen ; resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Oxygen plays such a critical role in the central nervous system that a specialized mechanism of oxygen delivery to neurons is required. Reduced oxygen tension, or hypoxia, may have severe detrimental effects on neuronal cells. Several studies suggest that hypoxia can induce cellular adaptive responses that overcome apoptotic signals in order to minimize hypoxic injury or damage. Adaptive responses of neuronal cells to hypoxia may involve activation of various ion channels, as well as induction of specific gene expression. For example, ATP sensitive K+ channels are activated by hypoxia in selective neuronal cells, and may play a role in cell survival during hypoxia/anoxia. Additionally, hypoxia-induced c-Jun, bFGF and NGF expression appear to be associated with prevention (or delay) of neuronal cell apoptosis. In this paper, these adaptive responses to hypoxia in neuronal cells are discussed to examine the possible role of hypoxia in pathophysiology of diseases.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular neurobiology 17 (1997), S. 289-304 
    ISSN: 1573-6830
    Schlagwort(e): Parkinson's disease ; dopamine ; dopamine-melanin ; apoptosis ; bcl-2 ; antioxidants
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Abstract 1. Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinson's disease (PD). It is assumed that the lethal trigger is the accumulation of oxidative reactive species generated during metabolism of the natural neurotransmitter dopamine. 2. We have recently shown that dopamine is capable of inducing programmed cell death (PCD) or apoptosis in cultured postmitotic chick sympathetic neurons and rat PC12 pheochromocytoma cells. 3. The bcl-2 gene encodes a protein which blocks physiological PCD in many mammalian cells. In an attempt to elucidate further the mechanism of dopamine toxicity, we examined the potential protective effect of bcl-2 in PC12 cells which were transfected with the protooncogene. 4. In our experiments, Bcl-2 producing cells showed a marked resistance to dopamine toxicity. The percentage of nuclear condensation and DNA fragmentation visualized by the end-labeling method following dopamine treatment was significantly lower in bcl-2 expressing cells. Bcl-2 did not protect PC12 cells against toxicity induced by exposure to dopamine-melanin. Extracts of PC12 cells containing Bcl-2 inhibited dopamine autooxidation and formation of dopamine-melanin. Furthermore, the presence of Bcl-2 protected cells from thiol imbalance and prevented thiol loss following exposure to dopamine. 5. The protective effects of Bcl-2 against dopamine toxicity may be explained, in part, by its action as an antioxidant and by its interference in the production of toxic agents. The possible protection by Bcl-2 against neuronal degeneration caused by dopamine may play a role in the pathogenesis of PD andmay provide a new direction for the development of neuroprotective therapies.
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  • 72
    ISSN: 1573-7217
    Schlagwort(e): affinity ; breast cancer ; estradiol ; receptor ; tissue estrogen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Breast tumors from postmenopausal women contain levels of estradiol similar to those in premenopausal patients even though serum estradiol levels fall by an order of magnitude upon cessation of ovarian function. The present study sought to examine enhanced uptake from plasma as one potential mechanism for maintenance of high tissue estradiol levels in postmenopausal patients. Accordingly, we used osmotic minipumps to continuously infuse estradiol (E2) at rates producing serum concentrations ranging from pre- to postmenopausal levels for two weeks to oophorectomized Sprague-Dawley rats bearing nitrosomethylurea-induced mammary tumors. We then measured E2 concentrations in various tissues and sera and reasoned that tissue affinities for estradiol could be directly calculated from in vivo measurements by adapting Scatchard analysis to steroid infusion data. Using this method, we demonstrated a very high affinity estradiol binding component with a Kd two orders of magnitude higher (i.e., 0.35 × 10-12 M) than determined with standard in vitro techniques. A second estradiol binding component with the expected Kdd of 1 × 10-10 M was also present. Estradiol bound to both classes of binding sites could be 98% displaced with diethylstilbestrol within a 6-hr period. In vivo steroid binding off-times calculated from log-linear slopes averaged approximately 60 min. These data demonstrated that the actual E2 binding affinity in target tissues in vivo, especially at low estrogen concentrations, is much higher than usually estimated from standard, in vitro estrogen receptor assays. These observations provide one mechanism to explain why estradiol concentrations remain high in breast cancer tissue from postmenopausal women and consequently can stimulate tumor proliferation.
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  • 73
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; elderly cancer patients ; age-related treatment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The medical records of all women (297 cases)with breast cancer ≥ 70 years of age,presenting at our Institute from January 1980 toDecember 1989, were reviewed. Data from 226 elderlywomen was compared to that from 100 stage-matchedpatients ≤ 50 years of age, presenting duringthe same 10-year study interval. Conservative surgery wassignificantly more frequent in young patients (71.1%) comparedto elderly women (26.1%) and radical mastectomy accordingto Halsted was undertaken in 34.3% of theelderly group compared to 8.9% of young patients(p 〈 0.001). Since ‘incidental’ diagnosis was significantlymore frequent in the elderly group (59.9% versus6.0%) (p 〈 0.001), primary care physicians mayplay an important role in the early diagnosisof breast cancer in the majority of elderlywomen.
    Materialart: Digitale Medien
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  • 74
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; ipsilateral breast tumor recurrence ; partial mastectomy ; radiotherapy ; risk factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To identify risk factors associated with an increasedrisk for ipsilateral breast tumor recurrence following breast-conservingsurgery, a cohort of 759 women with T1–T2tumors were studied. The majority of the patients(88%) had received postoperative radiation therapy to thebreast. Median follow-up time was 10 (range: 6–17)years. There was a 1–1.5% yearly increase inipsilateral breast tumor recurrences. For women 〈 50ys the cumulative recurrence rate at 10 yearswas 18% and for women ≥ 50 ys,9%. Node positive women had a cumulative breastrecurrence rate of 25% versus 10% for nodenegative women. Ten years postoperatively, irradiated patients hada cumulative recurrence rate of 11% versus 26%when no irradiation was given. The beneficial effectof radiotherapy was substantial during the first fourpostoperative years. The relative risk for an ipsilateralbreast tumor recurrence during this period was 4.5times higher than for non irradiated patients. However,the protective effect of radiotherapy decreased with time.After ten years the relative risk of ipsilateralbreast tumor recurrence was the same among irradiatedand non-irradiated patients although the number of eventsduring this period was low.Univariate analysis showed that seven factors were significantlyassociated with an increased risk of ipsilateral breasttumor recurrence, namely age 〈 50 ys, increasingtumor size, uncertain microscopic margins, axillary lymph nodemetastases, no postoperative tamoxifen treatment, premenopausal status, andno postoperative radiotherapy. Three factors remained independently significantafter multivariate analysis: age 〈 50 ys,no postoperative radiation therapy, and positive lymph nodes.In conclusion, radiotherapy reduced the breast recurrence rate,but the effect decreased with time. Node-negative women≥ 50 were a low risk-group for ipsilateralbreast tumor recurrence, with a cumulative risk at10 years of 9% without radiation therapy and5% with breast irradiation.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 43 (1997), S. 33-41 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; health services research ; small-area analysis ; tamoxifen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To describe the change in use oftamoxifen over time and across countries in Ontario.Methods: Data from the Ontario Drug Benefit (ODB)plan, Census Canada, and the Ontario Cancer Registry(OCR) were combined and analysed to determine ratesof tamoxifen use for females over 65 foreach county and the province overall, by year.Rates were analyzed by repeated measures ANOVA todetermine significance of changes over time. Consistency oftamoxifen use across counties was determined by theSpearman rank correlation coefficient, and overall variation betweencounties was described using three statistical techniques: Chi-squareanalysis, the extremal quotient (EQ), and the systematiccomponent of variation (SCV). Results: The number ofone-month tamoxifen prescriptions per incident case of breastcancer rose significantly from 13.51 in 1985 to20.54 in 1990 (p 〈 0.001) and to34.06 in 1992 (p=0.001). Viewed differently,the number of women over 65 receiving tamoxifenprescriptions per incident case of breast cancer changedfrom 1.91 in 1985 to 3.14 in 1990to 4.54 in 1992. Statistically significant variation inthe rate of tamoxifen prescribing was demonstrated betweenOntario counties in all three years by ChiSquared analysis (p 〈 0.0001). Both the EQand the SCV declined from 1985 to 1990,suggesting more uniform prescribing across the province. Littlechange in overall variation was seen between 1990and 1992. All counties over time tended toprescribe generic preparations more often and shifted from10 mg to 20 mg formulations. Conclusions: Thesignificant increase in the rate of tamoxifen useand trend towards more uniform prescribing across Ontariobetween 1985 and 1990 coincided with the publicationof two important documents outlining the benefits oftamoxifen in early breast cancer. Despite this trend,variation in tamoxifen use between counties remains. Therehas been little change in uniformity of prescribingsince 1990.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 43 (1997), S. 211-215 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; tumor necrosis factor ; mastectomy ; prognosis ; serum markers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The outcome of breast cancer is usuallydetermined by multiple factors. Serum tumor necrosis factoralpha concentration has been found to be increasedin the circulation of patients with malignancy. Thisstudy was designed with the aim to investigateany correlation between the serum tumor necrosis factoralpha and the clinicopathological fetures and furthermore evaluatethe prognostic significance of serum tumor necrosis factoralpha concentration in breast cancer. Methods: Forty consecutivepatients with invasive breast cancer undergoing modified radicalmastectomy were prospectively included and evaluated. Venous bloodsamples were collected before the surgery. Sera wereobtained by centrifugation, and stored at − 70°C until assayed. The control group consisted 30healthy, age-matched subjects. Serum concentrations of tumor necrosisfactor alpha were measured by the quantitative sandwichenzyme immunoassay technique. The data on tumor size,age, estrogen receptor status, lymph node status andTNM staging were reviewed and recorded.Results: The mean value of serum tumor necrosis factor alphain patients with invasive breast cancer was 1.47± 0.58 pg/ml and that of the controlgroup was 0.98 ± 0.37 pg/ml, and thedifference was significant (P 〈 0.01). With univariableanalysis, patients with maximum tumor size of 5cm or larger (P=0.03), more advancedTNM staging (P 〈 0.01); and more advancedlymph node status (P 〈 0.01) were shownto have significantly higher serum concentrations of tumornecrosis factor alpha. However, with multivariable analysis, TNMstaging appeared as the only independent factor (P〈 0.01) predicting the significant, higher serum concentrationsof tumor necrosis factor alpha. Conclusion: Preoperative evaluationof serum tumor necrosis factor alpha concentrations maybe a valuable parameter for reflecting the severityof staging for invasive breast cancer.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 43 (1997), S. 225-235 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; axillary lymph node dissection ; adjuvant radiotherapy ; responsible hospital ; survival
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A retrospective review is presented of 1353 consecutivepatients with histopathologically confirmed invasive breast carcinoma treatedradically with curative intent during the decade 1980–89.None had received adjuvant systemic therapy with hormonesor prolonged chemotherapy. The distribution of lymph-node negative(N−) and lymph-node positive (N+) patients was 75%and 25%, respectively. The treatment and outcome were analysed as regardsconventional prognostic parameters, in particular considering the axillarylymph-node status and the responsible hospital category (GeneralMunicipal Hospitals (MH)) versus Comprehensive Cancer Center (CC)). The most striking difference was detected as regardsthe number of examined lymph nodes. The mediannumber of nodes described at the MH was7, as compared to 14 at the CC(p 〈 0.001). In patients with pT1 tumoursthe highest rate of lymph-node positivity was observedwhen 10 or more axillary nodes were removed.Adjuvant radiotherapy reduced the loco-regional recurrence rate inthe N− patients, whereas only the regional recurrenceswere reduced among the N+ patients. The five-and 10-year tumor-related survival rates were 86% and76%, respectively, with no difference between the MHand the CC. As life-prolonging adjuvant hormone therapy and chemotherapy isnow available for patients with axillary lymph nodemetastases, it is important that patients with breastcancer are operated adequately with the aim toremove at least 10 axillary lymph nodes. Athorough examination of the axillary content should beperformed by the pathologist, and the number ofresected lymph nodes and metastases should be reported.The establishment of nation-wide standard criteria for themanagement of breast cancer is recommended.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 44 (1997), S. 83-89 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; capillary gas chromatography ; postmenopausal women ; urine steroids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Urinary steroid metabolites were measured by capillary gaschromatography in 22 postmenopausal women with operable breastcancer on day before the tumour excision andin 20 hospitalised control who were before anoperation from other cause than cancer. Serum dehydroepiandrosterone-sulphat(DHEAS) and testosterone (T) level were measured byradioimmunassay in the same groups and same time.There was no significant difference in the levelof urinary androgen metabolites. Pregnanediol level was significantlylower (P 〈 0.05) in cancer patients. Inthe 5 patients with positive axillary nodes thetetrahydrocortisol and α-cortolone levels were significantly (P 〈0.05) higher than in node negative ones. Therewas no significant differences in the serum DHEASand T levels. These results indicate that metabolicchanges are existing in postmenopausal patients which maybe a cause or a consequence of thedisease.
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  • 79
    ISSN: 1573-7217
    Schlagwort(e): CD44v6 ; breast cancer ; patients N0M0 ; metastasis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract New isoforms of CD44 with alternatively spliced exons have recently been described. Expression of exon v6 seems to be of particular interest. It has indeed been associated with poorer outcome of breast cancer patients with node invasion at diagnosis. However, no data were available for patients N0M0 (with neither metastasis nor node invasion at diagnosis). Moreover, previous statistical analyses were realized using immunohistochemical methods to detect CD44v6 expression although several variants with exon v6 have been described. We investigated expression of isoforms containing CD44v6 using an RT-PCR approach and a panel of 25 normal breast specimens, 10 mammary fibroadenomas, 8 cystic samples and 52 primary breast tumors (38 invasive N0M0). Normal breasts, fibroadenomas, and cysts all express the same variant, A (with exon v6 only), while several transcripts are amplified in tumors. Expression of variants other than A correlates with acquisition of a malignant phenotype. Invasive cancers also express additional variants in comparison with in situ carcinomas. Metastasis capacities seem to be associated with transcription of variants other than A but also with no transcription of some of them, variants D (with exons v6 and v10) and L (with exons v6 to v10). Expression of variants D and L correlates with higher percentages of disease-free survival and better outcome. Expression of CD44 splice variants with exon v6, as detected by RT-PCR, might be a useful prognostic factor for breast cancer. However, since the series size is small, our results need to be confirmed by later studies on a larger number of patients.
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  • 80
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; dehydroepiandrosterone sulfate ; estradiol ; postmenopausal Japanese ; progesterone ; sex hormone-binding globulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We measured serum levels of estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, and dehydroepiandrosterone sulfate (DHEAS) in 61 postmenopausal women drawn from female residents in a community in Japan to evaluate the relationships between these hormone levels and potential breast cancer risk factors. The information on reproductive history, body size, alcohol use, and physical activity was obtained by means of a self-administered questionnaire. There was a significant trend in increasing E2 level with increasing height after taking account of age and body mass index (BMI) (p for trend = 0.04). BMI was inversely associated with SHBG level after controlling for age (p for trend = 0.01). Decreasing progesterone with increasing BMI was observed after controlling age and history of hysterectomy (P=0.05). Alcohol consumption was positively associated with E2 level and there was a strong linear trend after controlling for age, height, and BMI (p for trend=0.001). Trend for increasing DHEAS with alcohol consumption was also statistically significant after controlling for age and history of hysterectomy (p for trend=0.01). Reproductive factors as well as physical activity were not related to any of the hormone levels.
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 45 (1997), S. 07-14 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; lumpectomy ; mastectomy ; QALY ; cost-utility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the last decade, breast cancer patients have enjoyed an increase inbreast conserving surgery (BCS). At present, modified radical mastectomy(MRM) and BCS offers equal expectations of survival. During the last fewyears, however, a drop in the frequency of BCS has been reported by severalauthors. Is this new trend due to economic concerns? To clarify the costs ofbreast cancer therapy (stage I and II), we review the literature and includea cost-utility and a cost-minimisation analysis comparing MRM and BCS. The treatment cost (per patient) of BCS and MRM in Norway was calculated at$ 9,564 and $ 5,596, respectively. Employing a quality of lifegain in BCS of 0.03 (0–1 scale) and a 5% discount rate, thecost per QALY in BCS compared to MRM was $ 20,508. In cost-minimisinganalysis, BCS and mastectomy followed by reconstructive surgery had a costof $ 10,748 and $ 8,538, respectively. This indicates that BCSremains within reasonable cost and should not be displaced by mastectomy oneconomic grounds.
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 42 (1997), S. 121-124 
    ISSN: 1573-7217
    Schlagwort(e): Hispanics ; breast cancer ; ethnicity ; socioeconomic status
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the Department of Defense health care system,all women have the same ability to accesshealth care. Thus, there should be no racialdifferences in stage at diagnosis solely based onability to seek health care. A retrospective reviewof breast cancer cases from 1980–1992 was conductedto determine if there were any differences instage at diagnosis between Caucasian and Hispanic females.Data was available for 6134 Caucasian and 182Hispanic females. Although not statistically significant, Hispanic femaleshad fewer Stage I (41% versus 53%) andmore Stage IIA (37% versus 28%) breast cancersthan Caucasian females. Hispanic females had statistically fewertumors ≤ 1 cm (p 〈 0.001). Caucasianfemales were older (median age 58 years) atpresentation than Hispanic females (median age 51 years).Significantly (p = 0.002) more Hispanic females (44%)were 〈 50 years old compared to Caucasianfemales (28%). When access to care is notan issue, Hispanic females tended to present ata more advanced stage although this did notreach statistical significance. Hispanic females with breast cancerwere significantly younger than Caucasian females.
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 45 (1997), S. 81-95 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; TGFβ ; activation ; resistance ; receptors ; tamoxifen ; chemoprevention
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Transforming Growth Factor-β (TGFβ) is the most potent knowninhibitor of the progression of normal mammary epithelial cells through thecell cycle. During the early stages of breast cancer development, thetransformed epithelial cells appear to still be sensitive toTGFβ-mediated growth arrest, and TGFβ can act as an anti-tumorpromoter. In contrast, advanced breast cancers are mostly refractory toTGFβ-mediated growth inhibition and produce large amounts of TGFβ,which may enhance tumor cell invasion and metastasis by its effects onextracellular matrix. We postulate that this seemingly paradoxical switch inthe responsiveness of tumor cells to TGFβ during progression is theconsequence of the activation of the latent TGFβ that is produced anddeposited into the tumor microenvironment, thereby driving the clonalexpansion of TGFβ-resistant tumor cells. While tumor cells themselvesmay activate TGFβ, recent observations suggest that environmental tumorpromoters or carcinogens, such as ionizing radiation, can cause stromalfibroblasts to activate TGFβ by epigenetic mechanisms. As thebiological effects of the anti-estrogen tamoxifen may well be mediated byTGFβ, this model has a number of important implications for the clinicaluses of tamoxifen in the prevention and treatment of breast cancer. Inaddition, it suggests a number of novel approaches to the treatment ofadvanced breast cancer.
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  • 84
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; chemotherapy ; mitoxantrone ; fluorouracil ; folinic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In this phase II trial we have evaluatedthe activity and toxicity of a combination regimencontaining mitoxantrone, L-leucovorin, and fluorouracil in patients withadvanced breast cancer pretreated with anthracyclines. Forty-six patientswere included into the study; they received atotal of 227 cycles of chemotherapy. Median agewas 63 years (range 34–78), median performance statuswas 80 (range 60–100). Visceral metastases were presentin 37 patients, 6 patients had bone involvementonly, while 3 patients had soft tissue/lymph nodedisease. Median number of previous chemotherapy regimens foradvanced disease was 2 (range 1–3). Ten patientshad anthracycline primary resistance (progressive disease during treatment).Twenty-three patients received mitoxantrone 12 mg/sqm day 1;fluorouracil 370 mg/sqm and L-folinic acid 100 mg/sqmdays 1–3 administered every three weeks. Another groupof 23 patients were treated with the sameregimen using a prolonged 5FU/L-FA schedule (5 days).Two complete responses and 6 partial responses wererecorded with the 3-day schedule; 7 partial responsesin the 5-day schedule (overall response rate 32.6%,95% C.I. 19–46%). Two partial responses were observedin patients with anthracycline primary resistance. Median responseduration was 9 months (range 3–16). Hematologic toxicitywas mild: grade 3–4 leukopenia was recorded in5 patients, grade 3–4 thrombocytopenia in 3 patients.Grade III–IV stomatitis and diarrhea was recorded in4 and 5 patients respectively (all receiving the5-day 5-FU/L-FA schedule). Cardiac toxicity was observed intwo cases. This regimen proved active in advancedbreast cancer following anthracycline-containing chemotherapy, and the 3-dayschedule could be offered to such patients withacceptable toxicity.
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 46 (1997), S. 255-278 
    ISSN: 1573-7217
    Schlagwort(e): xenografts ; breast cancer ; cell lines ; resistance ; cytotoxic drugs ; synergy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Considerable effort has been placed into the identification of new antineoplastic agents to treat breast cancer and other malignant diseases. The basic approaches, in terms of model selection, endpoints, and data analysis, have changed in the previous few decades. This article deals with many of the issues associated with designing in vivo studies to investigate the activity of experimental and established compounds and their potential interactions. Endpoints for both in situ and excision assays are described, including approaches for determining cell kill, tumor growth delay, survival, and other estimates of activity. Suggestions for approaches that may limit the number of animals also are included, as are possible alternatives for death as an experimental endpoint. Other concerns, such routes for drug administration, drug dosage, and preliminary assessments of toxicity also are addressed. Statistical considerations are only briefly discussed, since these are addressed in detail in the accompanying article by Hanfelt (Hanfelt JJ, Breast Cancer Res Treat 46:279-302, 1997). The approaches suggested within this article are presented to draw attention to many of the key issues in experimental design and are not intended to exclude other approaches.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 46 (1997), S. 215-223 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; monounsaturated fats ; n-3 fatty acids ; n-6 fatty acids ; saturated fats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We review two meta-analyses of experiments on dietary fat and mammary tumor incidence in rodents, emphasizing a recent meta-analysis on the effects of different types of dietary fatty acids. This analysis shows that n-6 polyunsaturated fatty acids most strongly enhance mammary tumors in rodents, and saturated fats also enhance these tumors but less strongly. Further, the analysis shows that energy restriction protects against mammary tumors. We show that these results agree qualitatively with estimates of effects on human breast cancer derived from international correlations.
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  • 87
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; invasion ; zymography ; MMP-9
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.
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  • 88
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; metastatic ; filgrastim ; mitoxantrone ; 5-fluorouracil ; leucovorin ; chemotherapy ; CSFs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Based on reports of substantial antitumor efficacy of the combination of mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial was performed to attempt augmentation of the dose of DHAD with filgrastim support. The doses and schedules, all intravenous, were DHAD (total dose divided over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2;III, 24 mg/m2; IV, 32 mg/m2;and LV, 300 mg, followed by FU, 350 mg/m2;,on days 1–3. Filgrastim was given at 5 μg/kg/day subcutaneously on days 4–13. The planned cycle length was 21 days. Three or 4 patients were to be entered at each dose level and the maximum tolerated dose (MTD) was defined as thedose immediately below that which resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an apparent MTD was identified, an additional 6 patients were to be entered. Twenty patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts; IV: 4 pts. The major toxicity was found to be cumulative thrombocytopenia with platelet counts ≤ 20,000/μL occurring after cycle 1 at all levels beyond level I and five pts (25%) were removed from treatment solely because of platelet toxicity. Additional serious toxicities included grade 4 stomatitis in one patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts assessed, 5 (29%)achieved an objective response. The response rates in this study are lower than reported in the literature for the combination of DHAD, 5FU, LV and this may be related to the fact that only 40% of the patients were removed from protocol treatment because of disease progression. On the basis of limited DHAD-dose augmentation, toxicities observed, and modest response rate, the filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be recommended for further development for treatment of women with metastatic breast cancer.
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  • 89
    ISSN: 1573-7217
    Schlagwort(e): age at first full-term pregnancy ; breast cancer ; etiological risk factors ; family history ; oral contraceptives ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Several risk factors for the etiology of breastcancer have also been correlated with the prognosisof breast cancer. However, the published studies haveyielded conflicting results. Women under 71 years of age with stageI, II, or III breast cancer were eligiblefor inclusion in a clinical study. 866 patientswith breast cancer entered the study, of whom463 had positive lymph nodes. Survival was analysed using Cox's proportional hazards model.Age at menarche, parity, age at menopause andfamily history were not consistently related to survival.Young age at first full-term pregnancy was relatedto decreased survival (adjusted relative risk (RR): 1.69,95% confidence intervals (95% CI): 1.04–2.68), but itcannot be excluded that this result was dueto chance alone. Use of oral contraceptives wasnot correlated with survival (RR: 1.10, 95% CI:0.80–1.51) nor was family history (RR: 0.93, 95%CI: 0.66–1.30). This study provided little support for the hypothesisthat risk factors for breast cancer are relatedto survival.
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  • 90
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 44 (1997), S. 75-82 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; incidence ; Japan ; risk factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The incidence rate of breast cancer in Japanrose more than two-fold from 1959–60 to 1983–87.To assess to what extent this increase canbe explained by changes in the prevalence offour major risk factors of breast cancer (i.e.age at menarche, age at first birth, ageat menopause, and parity), we estimated the probabilityof developing breast cancer based on the jointdistribution and relative risks of these four riskfactors. The age-specific incidence rate during 1959–60 reportedby the Miyagi Prefectural Cancer Registry was usedto estimate the baseline hazard rate for womenwithout the four risk factors in the sameage group. Assuming that the baseline hazard rateis constant during all periods, we calculated theexpected incidence rates during the periods of 1959–60,1962–64, 1968–71, 1973–77, 1978–81, and 1983–87 for eachage group. Large discrepancies were noted between theobserved and expected incidence rates during 1983–87 inall age groups. The change in the jointdistribution of the four risk factors accounted forless than 40% of the increase observed from1959–60 to 1983–87, suggesting the effects of otherpowerful risk factors.
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 44 (1997), S. 1-22 
    ISSN: 1573-7217
    Schlagwort(e): apoptosis ; cell cycle ; amplification ; overexpression ; breast neoplasia ; c-Myc
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The proto-oncogene c-myc is commonly amplified and overexpressed in human breast tumors, and the tumorigenic potential of c-myc overexpression in mammary tissue has been confirmed by both in vitro and in vivo models of breast cancer. However, the mechanisms by which Myc promotes tumorigenesis are not well understood. Recent evidence indicates that Myc can promote cell proliferation as well as cell death via apoptosis. These studies provide new insight and impetus in defining a role for c-Myc in breast tumorigenesis and may point toward novel targets for breast cancer therapy.
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  • 92
    ISSN: 1573-7217
    Schlagwort(e): Bcl-2 ; breast cancer ; Ki-S1 ; tamoxifen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Ki-S1, a marker of proliferation, and bcl-2, thegene product of which is an antagonist ofapoptosis, have been measured in 51 ER-positive primarybreast cancers before and during tamoxifen treatment andthen related to clinical response. Both markers weredetected in the majority of tumours before treatmentand, quantitatively, initial expression of Bcl-2 protein, butnot Ki-S1, was significantly related to the percentagereduction in tumour volume as assessed by ultrasound. Staining for both markers was lower in posttreatment samples than in those taken prior totreatments, but concordant decreases in staining indices wereseen in only 11 of the 51 tumours.The results demonstrate, using clinical material, that theresponse to tamoxifen may involve changes in proliferationand/or susceptibility to cell-death.
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  • 93
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; drug response ; induction chemotherapy ; p-glycoprotein
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    Breast cancer research and treatment 42 (1997), S. 87-90 
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; ductal carcinoma in situ ; Gadolinium-DTPA ; galactography ; magnetic resonance imaging ; nipple discharge
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A new method of galactography using magnetic resonance imaging for a patient with nipple discharge is developed. The method is as follows; coronal T1-weight images are obtained after an injection of contrast medium of 1 mmol/L Gd-DTPA directly into the discharge duct, before and after rapid intravenous infusion of Gd-DTPA. A case of a 29-year-old woman with ductal carcinoma in situ with minimal invasion is reported, in which all portions of the entire discharge duct system is clearly shown as viewed from the surface and the surrounding area is enhanced with Gd-DTPA. The enhanced area is coincidental with the extent of the disease. This magnetic resonance galactography for patients with nipple discharge may be used to supplement conventional mammography and/or galactography especially for the evaluation of the extent of disease, although it is somewhat inferior to mammographic galactography in terms of differential diagnosis of ductal disease.
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  • 95
    ISSN: 1573-7217
    Schlagwort(e): apoptosis ; Bcl-2 ; breast cancer ; estrogen receptor ; intraductal cancer ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of estrogen receptor (ER) and bcl-2(Bcl-2), an apoptosis protective oncogene, in normal andcancerous breast duct epithelia was immunohistochemically examined infresh frozen tumor tissues from 142 Japanese breastcancer patients. The clinico-pathological characteristics and the diseasefree survival of the patients were analyzed. Theexpression of both the proteins was also observedin intraductal components of breast cancer. Although lessthan 1% of normal duct epithelia expressed ER,Bcl-2 was diffusely expressed. The expression of boththese proteins in breast cancer significantly correlated witheach other. Their expression significantly correlated negatively withtumor size but not with lymph node status.The papillo-tubular sub-type of invasive ductal carcinoma expressedBcl-2 significantly more frequently than the solid-tubular sub-type.Patients with Bcl-2 expressing tumors survived without recurrencesignificantly more than those with tumors exhibiting reducedexpression. Papillary-cribriform type intraductal componentsexpressed both those proteins more often than the solid-comedo type.
    Materialart: Digitale Medien
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  • 96
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; endocrine therapy ; follow-up ; metastatic ; tamoxifen
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Purpose: To examine the outcomes of endocrine naive patients treated with tamoxifen as initial endocrine therapy for metastatic breast cancer. Data were obtained from the long-term follow-up of two previously published randomized trials. Patients and methods: All patients received tamoxifen 20 mg po in a single daily dose. Eligibility required patients to be age ≥ 18, performance status 0—3, and estrogen or progesterone receptor positive or unknown. Patients were ineligible if they had any prior endocrine therapy in either the adjuvant or metastatic setting. Results: 156 patients have been followed for a median of 8.3 years. Median age was 61 years, 83% were ≥ 50 years, 84% performance status of 0–1, 43% were both ER and PR positive, 33% had prior chemotherapy, 62% had a disease-free interval of 〉 2 years, and 59% had only one metastatic site. The complete (14%) and partial (6%) response rate for 147 evaluable patients was 20% (95% CI for CR + PR of 14–27%). Multivariate analysis revealed that improved response was related to soft tissue involvement and positive PR status. The majority of patients with soft tissue, nodal or lung metastases had responses noted within three months. Median time to disease progression was 6.7 months. Multivariate analysis revealed that older patients, those with one metastatic site and those with positive PR status had the longest time to progression. Median survival was 27.2 months. Better performance status, fewer metastatic sites and being PR positive were associated with significantly improved survival. Conclusion: The patient population in this series is not likely to be studied in future trials because of the wide use of tamoxifen in the adjuvant setting. In a small percentage of patients with metastatic breast cancer, tamoxifen therapy is associated with prolonged remission and survival. Pretreatment characteristics can help identify such patients.
    Materialart: Digitale Medien
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  • 97
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; body mass index ; parity ; physical activity ; pre-menopause ; post-menopause
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To further clarify risk factors for breast cancerin Japanese women, a self-administered questionnaire was completedby 157 cases with histologically confirmed breast cancerfrom 1989 to 1993 and by 369 ageand residential area matched controls in Gifu, Japan.Conditional logistic regression model was used to assessthe relations. Multivariate analyses showed that breast cancerrisk decreased with body mass index for premenopausalwomen (RR=0.45; 95% CI=0.22–0.92for BMI ≥ 23 vs. 〈 21 (kg/m2)),but the risk increased with body mass indexfor postmenopausal women (RR=1.98; 95% CI= 0.86–4.55 for BMI ≥ 24 vs. 〈21.5 (kg/m2)). The risk increased with a smallnumber of births in pre- and post-menopausal women(1.83; 1.11–2.99 and 6.06; 2.40–15.3 for 1–2 birthsand nulliparity, respectively, vs. ≥ 3 births). Ex-or current smoking increased the risk of breastcancer (2.31; 1.19–4.49). Reduced risk of premenopausal breastcancer was associated with high energy expenditure inphysical activity during teenage, although the trend wasnot statistically significant.
    Materialart: Digitale Medien
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  • 98
    ISSN: 1573-7217
    Schlagwort(e): basic fibroblast growth factor (bFGF) ; breast cancer ; cathepsin D ; MCF-7 ; mitogenic activity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Mitogenic activity toward MCF-7 cells of two immunoreactive(high-molecular-weight form bFGF, HMW-bFGF; and 16-K bFGF, havingthe same molecular weight as recombinant bFGF) purifiedfrom pooled sera of breast cancer patients byheparin-affinity chromatography and gel filtration was investigated. Themitogenic activity of 16-K bFGF toward the cellswas equal to that of recombinant bFGF, whereasthe mitogenic effect of HMW-bFGF was weak. Mostof the mitogenic activity of these two bFGFswas neutralized by anti-bFGF antibody. Also, the mitogenicactivity of both HMW-bFGF and 16-K bFGF wasmarkedly enhanced by aspartyl protease (cathepsin D), whichis secreted in excess by breast cancer cellsand is responsible for the enzymatic degradation ofthe extracellular matrix (ECM). By an enzyme immunoassay,we detected cathepsin D-mediated release of recombinant bFGFpreviously bound to the ECM of MCF-7 cellsinto the conditioned medium, and also observed cathepsinD-mediated proteolysis of HMW-bFGF to release free 16-KbFGF. These results suggest that 16-K bFGF isthe bFGF molecule itself in the blood andthat HMW-bFGF is a circulating form of bFGFin blood whose mitogenic activity is regulated bycathepsin D.
    Materialart: Digitale Medien
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  • 99
    ISSN: 1573-7217
    Schlagwort(e): breast cancer ; immunohistochemistry ; HSP70 ; PCNA ; prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A series of 80 female patients undergoing surgeryfor primary breast ductal infiltrating carcinoma not otherwisespecified (NOS) was immunohistochemically studied in order toverify any relationships between Proliferating Cell Nulear Antigen(PCNA) immunostaining, Heat Shock Protein 70 (HSP70) immunoreactivity,and several clinicopathological predictors.Positive PCNA scores (〉 20% of strongly immunopositivemalignant nuclei) were observed in neoplastic cells' nucleiin 13 tumors (16.25%) and were intimately associatedwith axillary nodal involvement (p=0.0131), relativelyhigh tumor grades (p=0.0016), increased tumorsize (p=0.0312), and low or negativelevels of estrogen receptors (p=0.0323). HSP70positive immunoexpression in malignant cells' cytoplasm (percentage ofHSP70 immunoreactive cells 〉 10%) was detected in33 samples (41.25%). It correlated significantly with presenceof axillary lymph nodal metastases (p=0.0033)and rather poor tumor differentiation (p=0.0014),whereas an association of borderline statistical significance emergedbetween HSP70 immunoreactivity and high progesterone receptor status(p=0.0637).PCNA positive immunostaining demonstrates the tumors' proliferative fractionand might be used as an indicator ofincreased malignant potential in breast cancer since itwas associated with four adverse prognosticators. HSP70 immunodetectionis a probable marker of the biological stressexperienced by breast cancer cells, since it wasrelated to relatively high tumor grades. Since bothproteins may potentially predict disease outcome, their prognosticsignificance must be validated by direct relation tosurvival. A multivariate statistical analysis including the variableswith which both proteins were associated will revealany possible independent prognostic value of PCNA andHSP70 immunostaining in local, ductal invasive breast cancerNOS.
    Materialart: Digitale Medien
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  • 100
    ISSN: 1573-7217
    Schlagwort(e): midkine ; breast cancer ; growth factor ; truncated form ; RT-PCR ; immunohistochemical analysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The expression of midkine (MK), a growth/differentiation factor,was assessed in 34 surgically resected specimens ofprimary breast cancer or mastopathy. Using reverse transcriptase-polymerasechain reaction (RT-PCR) analysis, all of the non-cancerousand cancerous tissues were found to express MKexcept for one breast cancer specimen. Northern blotanalysis revealed that MK mRNA was also expressedin the normal breast tissues examined. Immunohistochemical analysisof the MK protein was performed on alimited number of the specimens, showing that somecancerous tissues were immunoreactive with anti-MK antibodies. Furthermore,using RT-PCR analysis, expression of not only thewild-type but also a truncated form of MK,which was recently found in various human tumorcell lines, was detected in 6 of 26cancerous tissues but not in non-cancerous tissues.
    Materialart: Digitale Medien
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