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Biomedical subjects

C Dittrich

Publications and source records attributed to C Dittrich.

At least 73 records · Page 4Linked to original sources

Clonogenic growth in vitro: an independent biologic prognostic factor in ovarian carcinoma.

A retrospective analysis was performed to investigate the prognostic value of growth in a human tumor clonogenic assay system for 84 ovarian cancer patients. A significant difference in survival probability (determined by the method of Kaplan-Meier) was found by univariate analysis between patients with ovarian carcinoma whose tumors manifested clonogenic growth (defined as growth of greater than or equal to five colonies per plate) and patients whose tumors did not grow. Clonogenic growth in vitro was associated with worse prognosis (P = .007, log-rank test). A number of generally accepted prognostic factors, International Federation of Gynecology and Obstetrics (FIGO) stage (P = .003), residual tumor mass (P less than .001), and grade (P = .011), were also of prognostic importance in our patient population. Multivariate analysis, based on the Cox regression model, identified clonogenic growth as a significant independent prognostic parameter in ovarian carcinoma (P = .031), in addition to the conventional risk factors. Estimation of survival of individual patients was best accomplished by combining the factors of residual tumor mass (P less than .05), age (P less than .01), and clonogenic growth (P less than .05) (in sequence of decreasing potential of risk).

Aged↗

The effects of dimethyl sulfoxide and retinoic acid on the cell growth and the phenotype of ovarian cancer cells.

We have compared the in vitro effects of the differentiation inducers dimethyl sulfoxide (DMSO) and retinoic acid (RA) on a polyclonal human ovarian cancer cell line (HOC-7). Density gradient fractionation of untreated cells reveals that a proportion of rapidly growing, polygonal cells with medium density is capable of spontaneous reversion into a slowly growing low-density phenotype with flattened morphology similar to non-transformed human ovarian surface epithelial cells. Clonal expansion of these low-density cells proves that the observed characteristics are stable for prolonged culture periods. Exposure of HOC-7 cells to DMSO and RA or removal of the serum from the medium is effective in enhancing the proportion of these low-density cells. Application of DMSO causes the cells to become flattened and elongated, and to develop rod-like protrusions. In these cytoplasmic extensions thick filament bundles are dominant. Immunofluorescence studies demonstrate that both untreated low-density subclones and DMSO-treated polyclonal cells are much more reactive for cytokeratin than medium-density subclones or untreated parental cells. Furthermore, immunocytochemistry and fixed-cell ELISA reveal 2- to 5-fold greater amounts of desmoplakins I and II and of fibronectin in low-density subclones and in DMSO-treated cells as compared to medium-density subclones and control cultures. RA exerts weaker effects on the phenotype of the cells. Both inducers reduce DNA synthesis and inhibit the anchorage-dependent and the anchorage-independent cell growth in a dose- and time-dependent manner. The restoration of the original morphology and growth rate after removal of the differentiation-inducing agents proves that the observed changes are reversible; this indicates that the cells do not become terminally differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma].

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Euthanasia--limits of therapy in oncology].

Nowadays progress in medicine keeps human beings alive more frequently in hopeless and depressing situations associated with physical discomfort and pain for a long time. This situation, which is at least partly caused by medical treatment, should be generally reviewed, in particular with respect to the treatment of cancer patients. This principles of action or non-action should be re-examined at intervals retrospectively and continuously adapted to new developments.

Austria↗

Analysis of factors influencing clonogenic growth in vitro of cells from ovarian carcinoma patients.

Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%.

Agar↗

The role of chemotherapy including ifosfamide for ovarian carcinoma. Austrian Collab. Ovarian Cancer Study Group.

On the basis of the results of earlier studies, 30 departments of gynecology have been cooperating nationwide in Austria since 1980 to promote the use of adjuvant chemotherapy after surgery for cure of ovarian carcinoma in early stages and the role of lymph node dissection and of second-look operation. Results recorded in more than 160 patients treated with adjuvant chemotherapy after so-called radical surgery performed in disease stages I and II demonstrate that only highly differentiated tumours in stage Ia can be cured by surgery only with no further adjuvant treatment. This underlines the necessity for staging. More than 200 patients with TNM stages III and IV were randomized after debulking surgery to receive treatment with different kinds of drug combinations to compare the therapeutic efficacy of a sequential alternating drug regimen consisting of Adriamycin-cisplatin + vincristine-cyclophosphamide + high-dose methotrexate with that of the combination of Adriamycin-cyclophosphamide and that of Adriamycin-cisplatin. High-dosed ifosfamide was also used in pilot studies.

Cyclophosphamide↗

Phase I-II study on weekly administration of pirarubicin in patients with metastatic breast cancer.

A phase I-II study of weekly low-dose pirarubicin was performed in 19 patients with advanced breast cancer. The goal was to establish the optimal dose intensity, i.e., the maximal dose applicable at tolerable toxicity within the intended schedule. Each of the four different dose groups used (20, 24, 25, and 27 mg/m2) comprised 4-5 patients. In over 47% of patients, objective remissions were obtained (confidence interval 26%; 71%) including one complete and eight partial remissions; the median duration of remission was 41 weeks (range 16-72), and the median time to reach remission was 12 weeks (range 6-36). Efficacy of treatment was more dependent on prior chemotherapy than on pirarubicin dosage. The weekly i.v. push injection of the drug was easily applicable at an outpatient clinic and well tolerated. WHO grade 3 was the highest toxicity observed for leukopenia (3/19), leukopenia associated with infection (1/19), nausea/vomiting (2/19) and alopecia (6/19). More severe myelosuppression was avoided by interrupting the weekly application until recovery of leukocytes to greater than or equal to 3.5 x 10(3)/mm3. No clinical signs of cardiotoxicity were observed. Generally, mild to moderate signs of cardiac dysfunction acquired during therapy were detected by special cardiac monitoring. Only in 3 of 19 patients was a cumulative dose of more than 550 mg/m2 surpassed. This was accepted as the upper limit for conventional anthracycline therapy. The median cumulative dose applied was 325 mg/m2/week (range 58.2-800.0). Because of maldistribution of prognostic factors, no dose-response relationship could be established. With respect to the total time for which each patient was studied, the dose group of 27 mg/m2 achieved the highest dose intensity with a median of 17.4 mg/m2/week (range 13.5-22.4). Therefore, the dosage of 27 mg/m2/week is recommended to be used in further phase II-III trials of weekly applied pirarubicin.

Adult↗

Mucin-like cancer-associated antigen (MCA) compared with CA 15-3 in advanced breast cancer.

Mucin-like cancer-associated antigen (MCA), a new tumor marker using the mouse monoclonal antibody b-12 is thought to be of value in the management of patients with breast cancer. In this study sera from 191 female patients with breast cancer (112 with progressive disease [PD] and 79 with no evidence of disease [NED]) were analyzed for MCA levels and compared with those of cancer antigen 15-3 (CA 15-3) in single determination and in combination with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). A cut-off level of 14 U/ml for MCA seems to be more appropriate than the recommended 11 U/ml to distinguish between PD and NED in patients with breast cancer. Although there was a fairly good correlation of MCA to CA 15-3, MCA was inferior in sensitivity and specificity to CA 15-3. Patients with osseous metastases and those with more than one metastatic site showed higher MCA levels than patients with visceral or soft tissue metastases, a fact which was comparable to CA 15-3. Combining MCA and CA 15-3 resulted in a gain in specificity but marked loss of sensitivity. The combination of MCA and CEA results also in a loss of sensitivity whereas the combination of CA 15-3 and CEA showed an increased specificity and only a negligible loss of sensitivity. The combination of MCA with TPA is of little value in the follow-up of breast cancer, as is the combination of CA 15-3 with TPA. The combination of CA 15-3 with CEA can be still recommended for follow-up for early detection of metastases in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The value of second-look operation in patients with advanced epithelial ovarian carcinoma.

A second-look operation was performed on 151 patients with stage III and IV epithelial ovarian carcinoma who had responded to primary surgery and chemotherapy. 19% of the 79 patients who appeared clinically to be free of disease had microscopic recurrences and 23% had macroscopic residual disease at a second-look operation. The 5-year survival rate for patients with no histological and for those with microscopic secondaries at second-look operation were 55% and 35% respectively (P = 0.45). Only patients with well or moderately well differentiated tumors and a small residual tumor mass at first operation had a good prognosis after a second-look operation even without further chemotherapy. Median survival after secondary debulking was 15 to 17 months and was independent in the radicality of the second-look procedure. Outside of clinical trials second-look laparotomy should therefore only be performed as a diagnostic procedure in patients with well or moderately well differentiated tumors who are left with a small residual tumor mass at the time of the first operation. Because this is a group of patients in whom chemotherapy can be discontinued after a negative second-look operation.

Carcinoma↗

Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma.

The prognostic influence of the integrity or the rupture of the capsule was examined in 60 patients with stage I epithelial ovarian carcinoma. After an average follow-up of 75 months (range 30-120 months) the probability of 5-year survival was 76% in both groups. Therefore, we conclude that rupture of the tumor during surgery has no influence on survival rates. Consequently, these patients should not be considered as belonging to the subgroup stage IC ovarian carcinoma, as suggested by the FIGO committee.

Carcinoma↗

Long-term remission in a patient with erythroleukemia following interferon-alpha treatment.

A patient in second relapse of acute erythroleukemia (AEL) was treated with 10 MU of recombinant interferon (IFN)-alpha subcutaneously for 24 days after he had failed standard chemotherapy. Besides fever up to 38.9 degrees C and a transient raise in liver function parameters, treatment was well tolerated but had to be discontinued because of a severe decrease in white blood cell and platelet count. After termination of IFN treatment, both cell populations showed a continuous rise during the following weeks and hemoglobin increased concomitantly. Partial remission could be reached as was demonstrated by a decrease in PAS-positive erythroblasts in bone marrow biopsy. Further studies with IFN in patients with AEL refractory to cytostatic chemotherapy are recommended.

Adult↗

The clinical course of lung metastases from breast cancer.

The clinical course of 50 breast cancer patients whose first metastases were found in the lungs was investigated. 18 months after the start of primary treatment 50% of the patients had developed pulmonary metastases (range: 0-81 months). In 23% of patients a solitary, and in 68% more than one, lung metastases were detected. After a median time of 4 months, in 56% of patients the disease had spread to further organs with bone (25%) and liver (17%) being the most frequent sites. First line management of lung metastases employed surgery, endocrine treatment, chemotherapy or a combination of these modalities. In 24% of patients a complete response was achieved, and in 11% a partial response, with an overall response rate of 35%. Median survival from detection of lung metastases was 13 months (range 4-123+). Patients with only a solitary lung metastasis survived for a median of 11.5 months as compared to 10.5 months for patients with more than one pulmonary metastases. Patients with a disease-free interval of more than 18 months survived significantly longer than patients with a disease-free survival of 18 months or less.

Adult↗

Toxicity and response to high-dose ifosfamide + mesna as salvage therapy for advanced breast cancer.

Twenty-six cycles of high-dose ifosfamide + mesna (HD-IFO + M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO + M over 24 h appeared to be the best tolerated. One partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.

Adult↗