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Biomedical subjects

M Untch

Publications and source records attributed to M Untch.

101 records · Page 6Linked to original sources

Rationale of combining radiation and interferon for the treatment of cervical cancer.

The recent surge of interest in the mechanisms of action of biomodulators, also known as biological response modifiers, offers a new avenue of approach in the treatment of cancer. The in vitro antitumor activities of these agents, such as interferons, when combined with chemo- or radiotherapy, have generated enthusiasm among clinicians for developing clinical trials. In recent years many antineoplastic agents have been investigated as neoadjuvant or adjuvant therapy for patients with cervical cancer in an attempt to improve local control and to decrease incidence of metastasis. Normal tissue tolerance limits the potential combinations of standard cytotoxic chemotherapeutic agents with radiation. Interferon used as a radiomodulator has been studied mainly for the treatment of lung cancer with promising results. In this paper we report the rationale of combining interferon and radiation for the treatment of patients with cervical cancer.

Animals↗

Contrast-enhanced MRI of the breast after limited surgery and radiation therapy.

OBJECTIVE: Posttherapeutic changes in the breast after tumorectomy (TE) and radiation therapy (RT) may mimic or obscure recurrent or new malignancies and thus interfere with conventional diagnostic studies. We investigated the enhancement of tissue during variable time intervals after therapy with contrast-enhanced MRI in 62 patients. MATERIALS AND METHODS: We report the results of 77 studies in 62 patients undergoing TE and RT. We include only those studies with at least 24 months of clinical and mammographic follow-up (n = 60) or histopathologic results (n = 17). RESULTS: Up to 9 months after therapy, differentiation between posttherapeutic changes and recurrence was frequently impossible because of the strong enhancement. Ten to 18 months after therapy, this posttherapeutic enhancement subsided slowly with some interindividual variations. After 18 months posttherapy, no significant enhancement was encountered in 30 of 32 cases. Diffuse or focal enhancement was present in all recurrent tumors and all recurrences were correctly diagnosed. Furthermore, 4 of 11 recurrences and 10 of 18 single recurrent foci were detected by MR alone, based on focal enhancement. CONCLUSION: Accordingly, contrast-enhanced MR is not recommended during the first 9 months after therapy. Nine to 18 months after therapy, it may be helpful in those two-thirds of cases where the scar does not enhance. If enhancement takes place (one-third of cases), it may represent either scar or tumor, and in such circumstances, enhanced MR is of no value. After 18 months, enhanced MRI has proven a valuable additional tool. By correctly detecting or excluding recurrent tumor, it can significantly improve diagnostic accuracy.

Breast↗

Comparative chemosensitivity profiles in three human breast cancer cell lines with the ATP-cell viability assay.

In this study the dose-response curves for doxorubicin, pirarubicin, 5-fluorouracil, 4-hydroperoxy-cyclophosphamide and taxol were obtained in three breast cancer cell lines (MCF-7, T47D and BT-20). The ATP cell viability assay was chosen to evaluate the chemosensitivity profiles and was a reproducible, practicable method to assess drug response in breast cancer cell lines. The IC50 values were calculated on the median effect principle and indicated that taxol was the most active drug tested in this study with a mean IC50 value of 0.02 microM. This in vitro effect correlated well with clinical observations in metastatic breast cancer where taxol proved to be a vary active drug. Pirarubicin was the second most active drug tested with an IC50 value 10 times less compared to that of doxorubicin. The results obtained with the ATP cell viability assay are promising, therefore further testing with drug combination chemotherapy and fresh human breast cancer tumor testing are warranted and ongoing.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Tumor-biological factors uPA and PAI-1 as stratification criteria of a multicenter adjuvant chemotherapy trial in node-negative breast cancer.

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

Biomarkers, Tumor↗

Tumour markers CEA and CA 15-3 as Prognostic factors in breast cancer--univariate and multivariate analysis.

Tumour markers are putative prognostic indicators for patients with breast cancer, but have not been elevated independently by multivariate analysis in a large patient number. In 550 patients with breast cancer without known metastases the levels of the serum tumour markers CEA und CA 15-3 were determined preoperatively and during follow-up. The prognostic relevance of these markers for recurrence (n = 128/487) and death of disease (n = 55/550) was evaluated in relation to established prognostic factors. In univariate analysis tumour size, lymph nodes, histological grading, age, hormone receptors, preoperative value of CEA (cut-off 2 ng/mL) and CA 15-3 (cut-off 25 U/mL) and their decrease of more than 33% within seven months after operation were significant for relapse. The results for death of disease were similar except for age. In multivariate analysis tumour size, lymph nodes and decrease of CEA > 33% (p < 0.001) were independent prognostic factors for recurrence. For overall survival tumour size, lymph nodes, histological grading and preoperative levels of CEA > or = 2 ng/mL (p = 0.038) and of CA 15-3 > or = 25 U/mL (p = 0.007) were independent prognostic factors. Pre- and postoperative values of the tumour markers CEA und CA 15-3 are strong independent prognostic factors for relapse and survival in breast cancer patients.

Analysis of Variance↗

Combined treatment of metastatic breast cancer (MBC) by high-dose chemotherapy (HDCT) and bispecific antibodies: a pilot study.

UNLABELLED: This pilot study analyzed the efficacy and toxicity of high-dose chemotherapy (HDCT), autologous stem-cell transplantation (ASCT) and subsequent immunotherapy with T-cell reinfusion and trifunctional antibodies (trAbs) in chemotherapy-sensitive patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: After leukapheresis and cryopreservation of T-cells, patients received 2 cycles of induction chemotherapy ET (epirubicin/paclitaxel) and 1 cycle of El (epirubicin/ifosfamide), followed by G-CSF and stem-cell harvest. After a final cycle of ET, responders (CR/PR) underwent HDCT (thiotepa 600 mg/m2/melphalan 140-180 mg/m2) and ASCT. Once reconstitution was achieved, T-cells were reinfused, followed by application of trifunctional antibodies with specificities anti-EpCAM X anti-CD3 and anti-Her2/neu X anti-CD3. RESULTS: Thirty-three patients were recruited into the study and 19, who had responded to initial chemotherapy, underwent HDCT and ASCT (4 CR, 15 PR, OR = 57.6%; 95% CI: 40-75%). Two early deaths were observed (1 toxic, 1 early progression). T-cell reinfusion and trAbs were given to 17 patients. TrAbs treatment resulted in intermittent fever, chills and elevated liver enzymes, which were seen in all patients. The median overall survival was 27.7 months (range: 5.9-82.6+). Patients who received 3 trAbs doses showed a trend towards an improved overall survival (47.2 vs. 22.4 months, p = 0.08 log rank). CONCLUSION: This pilot study has shown the feasibility of combining HDCT with immunotherapy in MBC. Further investigation of this approach is indicated.

Adult↗

Alkaline phosphatase isoenzymes in detection and follow up of breast cancer metastases.

Alkaline phosphatase isoenzymes in bone and liver metastases of breast cancer were determined in 637 patients and during follow up in 116 patients, by agarose gel electrophoresis. The activity of total alkaline phosphatase, gamma glutamyl transferase, CEA and CA 15-3 was also determined. The sensitivity of bone alkaline phosphatase in bone metastases detection was 39%, of electrophoresis (total alkaline phosphatase and specific isoenzymes) 48% and of enzymes and tumor markers together 85% (n = 62). For liver metastases gamma glutamyl transferase had the best sensitivity (100%, n = 19). Even though positive predictive value was only 6%, the sensitivity of liver alkaline phosphatase was 58% and of electrophoresis 94%. The determination of alkaline phosphatase isoenzymes is a non-invasive, in-expensive, reproductable and rapid method to detect progressive disease in breast cancer, especially in combination with the tumor markers CA 15-3 and CEA.

Alkaline Phosphatase↗