Biomedical subjects

W Kuhn

Publications and source records attributed to W Kuhn.

427 records · Page 24Linked to original sources

PubMedDate not supplied

Maintenance chemotherapy with oral treosulfan following first-line treatment in patients with advanced ovarian cancer: feasibility and toxicity.

PURPOSE: To evaluate the feasibility and toxicity of maintenance oral treosulfan chemotherapy for ovarian cancer patients after surgical treatment and response to first-line chemotherapy. PATIENTS AND METHODS: Thirty-nine patients were entered onto this trial. This was a pretreated patient population. The pretreatment consisted of radical surgery and chemotherapy. The treatment that immediately preceded oral treosulfan was standard-dose platin-based chemotherapy. Daily oral treosulfan was administered at a dose of 1250 mg for 5 consecutive days every five weeks for at least three cycles. All patients started daily oral treosulfan while in complete remission. RESULTS: A total of 322 cycles of oral treosulfan was administered, with a median of 6 cycles (range 3-24). Treosulfan in this schedule was generally well tolerated. The major toxic effects were leukopenia and thrombocytopenia, which, however, were manageable and rapidly reversible. There were no episodes of bleeding or leukopenic fever. No anti-emetic drugs were required. Alopecia was not observed, 20 patients had progressive disease (after 3-6 months: n = 8, after > 6 months: n = 12). The median survival for all patients was 24 (range 9.44+) months, and median time to progression 8 (range 3-24) months. CONCLUSIONS: Maintenance oral treosulfan was well tolerated in this pretreated patient population. In an attempt to further improve overall survival in ovarian cancer patients, prospective random assignment trials will be necessary to determine the benefit of this approach.

Administration, Oral↗

PubMedDate not supplied

Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer.

The prognostic value of various molecular markers, which adequately account for the tumor biology and disease behaviour of ovarian cancer, is still unclear. Recent studies have focused on the role of genes regulating the balance between proliferation and cellular suicide, apoptosis. In the present study, tumor tissue from 215 patients with ovarian cancer was immunohistochemically analysed for Bax- and Bcl-2-expression. There was an association between Bcl-2-expression (30%) and factors of favourable prognosis. In contrast, Bax-expression (47%) was related to bad clinical outcome, especially in cases without concomitant Bcl-2-expression. In patients with Bcl-2-positive/Bax-negative tumors, overall survival was significantly longer (p = 0.0379) than in patients with Bcl-2- and Bax-negative tumors. Respectively, expression of Bax without Bcl-2-expression was correlated with bad clinical outcome (p = 0.033). The difference in overall survival was most striking (p = 0.0007) between patients with Bax-positive/Bcl-2-negative and Bcl-2-positive/Bax-negative tumors. This could also be demonstrated for the various subgroups of different tumor grade and stage. It may be speculated, that alteration of the Bax/Bcl-2-balance may influence the clinical course by deregulation of programmed cell death and altered sensitivity to chemotherapy.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Hormonal treatment with sex steroids in women is associated with lower p105 serum concentrations.

BACKGROUND: In breast and ovarian cancer patients elevated serum levels of the oncoprotein p105 were detected. We examined the influence of endocrine factors on the p105 serum concentration. MATERIALS AND METHODS: The sera of 115 and non-pregnant women were analysed. Of the premenopausal women (n = 77) hormonal contraception was used by 30 women, and of the postmenopausal women (n = 33) there were 15 women using hormonal replacement therapy (HRT). The serum specimens were analysed by ELISA. RESULTS: Women with hormonal contraception had significantly lower serum levels than premenospausal controls (82-138 fmol/ml, median 109 fmol/ml vs. 103-183 fmol/ml, median 130 fmol/ml; P < 0.001). In postmenopausal women with HRT serum levels were significantly lower than in postmenopausal controls (88-136 fmol/ml, median 117 fmol/ml vs. 99-261 fmol/ml, median 148 fmol/ml; P < 0.001). CONCLUSIONS: Sex steroids seem to modulate c-erbB-2 activity. These results are important with regard to clinical studies on p105 oncoprotein in cancer patients.

Contraceptives, Oral, Hormonal↗

PubMedDate not supplied

Effects of interfering and influencing factors on the analyses of p105 (c-erbB-2/HER-2) oncoprotein fragment in serum.

BACKGROUND: The 105 kDa extracellular domain of c-erbB-2 encoded protein p185 is detectable in serum. Elevated p105 serum levels were found in patients with breast and ovarian cancer and in pregnancy. The effects of interfering and influencing factors on the measurement are still unclear. MATERIAL AND METHODS: We used an ELISA based on the monoclonal capture antibody OD-3 and investigated possible interfering factors, like changing transporting and storing conditions of blood and serum samples. In order to evaluate a normal range of p105 serum values we examined 71 healthy women. RESULTS: In our tests we found no influence on the reproducibility of results by changing transporting and storing conditions. We could not find any dependency of p105 serum values on the menstrual cycle or the age of controls. Postmenopausal women showed significantly higher serum values than premenopausal women (p = 0.0127). CONCLUSIONS: Clinical interpretation of female p105 serum values requires comparison with normal ranges when considering the menopause as an influencing factor.

Adolescent↗

PubMedDate not supplied

[Meaning of assimilation pelvis according to Kirchhoff in modern obstetrics].

OBJECTIVE: To what extent is the cesarean section indication "arrest of labour" due to pathological forms of the pelvis and what is the meaning of the assimilation pelvis in modern obstetrics. PATIENTS: NMR-pelvimetries were performed in 166 post partum women from June 1993 to August 1995. The patients were divided into 4 groups. Group 1: patients who had had cesarean section owing to arrest of labour (n = 56), group 2: patients who had had cesarean section due to breech presentation (n = 20), group 3: patients who had had cesarean section owing to another indication (threatening fetal asphyxia, multiple pregnancy, premature delivery, placental abruption, gestosis, n = 40), group 4: patients who had a spontaneous delivery (control group, n = 50). After analysing the NMR pictures all the pelves were alloted to one of the case studies according to their pelvic form. The diagnosis "assimilation pelvis" was made according to the criteria of Kirchhoff (1949). The four groups were compared and analysed. RESULTS: In group 1 an assimilation pelvis was found in 61%. The obstetrically most unfavourable canal pelvis occurred most frequently, amounting to 29%. In only 9% we found a contracted pelvis. In group 2 the proportion of the assimilation pelvis was even higher, rising to 65%. Only 35% of all pelves had a normal shape. In group 3 we found an assimilation pelvis in 50% of all cases. 66% of all patients with spontaneous delivery had a normal pelvis. An assimilation pelvis was found in 34%. In these cases duration of labour was prolonged by 4 hours on average (mean value: 9.5 hours). CONCLUSIONS: Due to its frequency in our days the assimilation pelvis plays a major obstetrical role. This is true in particular when there is a pathological course of labour. From this results that pelvic parameters other than the conjugata vera will be of diagnostic importance, especially those parameters which are able to characterise the assimilation pelvis with its high promontory, the steepness of the pelvic inlet, the lengthening of the birth canal and the decrease of the hollow of the sacrum. We take the view that the angle of the pelvic inlet, the pelvic inclination and the direct length of the pelvis are of outstanding importance.

Breech Presentation↗

PubMedDate not supplied

Intravenously administered acetylsalicylic acid in combination with low-dose heparin in acute ischemic stroke: a safety analysis.

Although therapy with acetylsalicylic acid (aspirin, ASA) is well established in secondary prevention of stroke, efficacy and side effects of this substance in acute stroke treatment are undetermined. ASA may be useful in acute cerebral ischemia because of its potential to prevent thrombus propagation and neuronal damage. A total of 268 patients with an acute cerebral ischemia, who were admitted to our stroke unit within 24 hours after stroke, were treated with intravenously administered ASA (0.5 g/day) in combination with low-dose heparin. The functional status of the patients was assessed after 1 month using the modified Rankin Scale. Eighteen (6.7%) patients died during the observation period. The functional status according to Rankin Scale was classified as stage 0 in 76 (28.3%), 1 in 59 (22.0%), 2 in 39 (14.6%), 3 in 32 (12.3%), 4 in 36 (13.4%), and 5 in 7 (2.6%) patients. A symptomatic secondary intracerebral hemorrhage was seen in one patient. Gastrointestinal symptoms were observed in 13 (4.8%) patients, including five instances of gastrointestinal bleeding. Further complications were allergic reactions to aspirin (one) and hematuria (one). Recurrent cerebral ischemia occurred in nine (3.3%) patients (five with transient ischemic attack or minor stroke) during the observation period. We conclude that treatment of acute ischemic stroke with intravenously applied aspirin in combination with low-dose heparin is safe. Efficacy of this therapy should be elucidated in a controlled trial.

Acute Disease↗

PubMedDate not supplied

Breast preserving surgery decision making.

Mammography, and in special cases MRT, allow the detection of DCIS and microcarcinomas. Breast preserving surgery needs intraoperative care for tumor free margins. Decision making under favourable and unfavourable conditions is discussed. Tumor grading is important with respect to locoregional recurrences. Improvements in breast cancer diagnosis are discussed in a separate paper in the same volume. The significance of c-erbB2 in pT1N0M0 stage has been determined in 472 cases. Within the c-erbB family, c-erbB2 has highest significance. p53 should also be evaluated with respect to tumor progress. In a few cases of malignant cystosarcoma phyllodes, p53 reaction was found in epithelial and mesenchymal cell systems. These results correspond to the results of Domagala et al (90) which show that vimentin positivity correlates with high proliferation, a high degree of malignancy and c-erbB2 positivity. Finally, the significance of angiogenesis with respect to the ineffective knot-formation for tumor cell transport and detachment of epithelia with apoptosis are discussed. The significance of proteolytic activity of cancer according to the results of Schmitt et al (89) is included in the discussion. Biochemical analysis seems to be much more effective for prediction of metastatic process as compared with immunohistochemical evaluations.

Breast Neoplasms↗

PubMedDate not supplied

Identification of low-risk node-negative breast cancer patients by tumor biological factors PAI-1 and cathepsin L.

In node-negative breast cancer, 70% of patients are cured by surgery alone and thus should be spared the necessity of systemic adjuvant treatment. Histomorphological and tumor biological prognostic factors may be employed to assess the patient's risk profile with regard to disease recurrence and death. To evaluate the relationship between tumor biological factors and the metastatic potential of primary breast cancer, proteolytic factors uPA, PAI-1, and cathepsin L, which are associated with tumor invasion and metastasis, were determined in breast cancer tissue extracts by ELISA and the values assessed by uni- and multivariate analysis as well as CART (classification and regression trees) in comparison with traditional prognostic factors. Cysteine protease cathepsin L, serine protease uPA, and the protease inhibitor PAI-1 were determined by ELISA in extracts of primary tumors of 103 node-negative breast cancer patients and values assessed by univariate and multivariate analysis in comparison with traditional prognostic factors (tumor size, steroid hormone receptor status, grading, vessel invasion, menopausal status). Median follow-up of patients still alive at time of follow-up was 56.5 months (range 34-88). PAI-1, cathepsin L, tumor size, grading, and steroid hormone receptor status but not uPA, vessel invasion, and menopausal status were of prognostic relevance for disease-free survival (univariate analysis). Multivariate analysis of disease-free survival (Cox proportional hazards model) disclosed PAI-1 (relative risk of 8.6, p = 0.0001) to be the only strong and statistically independent prognostic factor. By CART-analysis, however, the combination of PAI-1 (< or = 14 ng/mg protein) and cathepsin L (< or = 1,100 ng/mg protein) allowed the identification of a subgroup comprising 68% of the node-negative breast cancer patients having a very low risk of disease recurrence (2/70; incidence of 0.8% per year) versus the high-risk group with PAI-1 (> 14 ng/mg protein) and cathepsin L (> 1,100 ng/mg protein) showing an increased recurrence rate (14/33; incidence of 8.6% per year). We conclude that by the combined determination of PAI-1 and cathepsin L tumor levels low-risk node-negative breast cancer patients may be identified. These patients most probably will not benefit from systemic adjuvant therapy.

Adult↗

PubMedDate not supplied

Prognostic impact of tumor biological factors on survival in node-negative breast cancer.

Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients.

Biomarkers, Tumor↗

PubMedDate not supplied

Prognostic value of angiogenesis in mammary tumors.

Vessel density counting has been performed in a variety of tumors and used as predictive parameter for the tumor's malignant behavior (metastasis, five year survival). A number of studies have reported conflicting results on the predictive value of vessel density counts. We have quantitated the number of microvessels in routine pathology specimens of paraffin embedded mammary tumors and related these findings to the histopathological diagnosis. Average vessel density counts of vascular hot spots of malignant and benign mammary tumors were similar (34 +/- 15 vs. 31 +/- 10), though significantly higher as in the adjacent normal mammary tissue (12 +/- 5). Analysis of individual tumors, however, showed that significantly more malignant than benign tumors had vessel density counts beyond a defined cut-off value (50 microvessels/HPF). The results suggest that high counts may indeed serve as an independent prognostic parameter. In contrast, low counts may also be observed in malignant tumors and may, thus, not be used as negative prognostic factor.

Breast Neoplasms↗

PubMedDate not supplied

Early intensive and myeloablative adjuvant chemotherapy in women with high-risk breast cancer.

BACKGROUND: Women with breast cancer and > 10 positive lymph nodes have an unfavorable prognosis. The optimal combination and intensity of adjuvant chemotherapy is uncertain. Between July 1994 and December 1996 we treated 19 patients with early intensive followed by high-dose chemotherapy and autologous peripheral blood stem cell transplantation. PATIENTS AND METHODS: Patients were initially diagnosed with breast cancer and multiple positive lymph nodes. Induction chemotherapy consisted of two courses VP16, ifosphamide, cisplatin and epirubicin (VIPE) and one course of mitoxantrone, cyclophosphamide and thiotepa (MCT). Peripheral blood stem cells were mobilized after the first or second course of VIPE and retransfused two days after high dose chemotherapy. RESULTS: Stem cells were successfully collected in all patients. Major toxicities (WHO grade III and IV) were neutropenia, thrombocytopenia, alopecia, nausea, infections and mucositis. Hematopoietic recovery occurred in all patients with a median of 10 days for leukocytes and 13 days for platelets. No patient died of therapy-induced complications. The median observation time is 24 months. Two patients have relapsed, one with locoregional disease. The projected rate of patients with disease-free survival after three years is 88%. CONCLUSIONS: Early intensive and myeloablative chemotherapy followed by peripheral blood stem cell transplantation is a highly efficient and feasible protocol for high risk patients with breast cancer.

Adolescent↗

PubMedDate not supplied

Detection of p105 (c-erbB-2, HER2/neu) serum levels by a new ELISA in patients with ovarian carcinoma.

BACKGROUND: Immunohistochemical detection of the oncogene c-erbB-2 (HER2/neu) has been shown to be an important prognostic marker in ovarian cancer. In this study we evaluated a new developed polyclonal detector antibody-based ELISA for the extracellular domain of p185 to determine whether the soluble oncoprotein fragment p105 can be detected in the serum of ovarian cancer patients. MATERIALS AND METHODS: The relationship between p105 serum levels and various tumor parameters in 53 patients with newly diagnosed, untreated ovarian cancer was studied. Serum specimens were obtained prior initial surgery, and p105 levels were determined using a new developed, polyclonal detector antibody-based human neu quantitative ELISA assay. RESULTS: Using the polyclonal detector antibody-based ELISA, elevated p105 serum levels were not related to tumor stage, grade, histology and residual tumor after primary surgery. CONCLUSIONS: These results suggest that particular statements concerning the preoperatively taken p105 level using the polyclonal antibody-based ELISA in patients with primary ovarian cancer cannot be brawn yet.

Adult↗

PubMedDate not supplied

Wertheim's hysterectomy after neoadjuvant carboplatin-based chemotherapy in patients with cervical cancer stage IIB and IIIB.

BACKGROUND: To improve local response and survival, a prospective study was designed to determine the effects of neoadjuvant chemotherapy in the management of cervical carcinoma stage IIB and IIIB. PATIENTS AND METHODS: Fourteen patients were treated with preoperative neoadjuvant chemotherapy. Three courses of carboplatin were administered in combination with ifosfamide in 11/14 patients, whereas 3 patients received three courses of carboplatin and paclitaxel. RESULTS: After neoadjuvant chemotherapy, there were 8/14 clinical responses while 6/14 patients had no change. In 8 cases, Wertheim's hysterectomy was possible after neoadjuvant chemotherapy. Six of these 8 patients are still alive after a duration of 32 months median follow-up, 2 patients died of metastatic disease. In 6 cases with no change after chemotherapy, Wertheim's hysterectomy was impossible. In this subgroup, the median survival time was 15.5 months, and 4/6 patients died of metastatic disease. CONCLUSIONS: Neoadjuvant chemotherapy with carboplatin/ifosfamide or carboplatin/paclitaxel is safe, well-tolerated, effective and useful to enable Wertheim's hysterectomy.

Adult↗