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Biomedical subjects

A Pfleiderer

Publications and source records attributed to A Pfleiderer.

At least 91 records · Page 5Linked to original sources

In vitro responsiveness of ovarian epithelial carcinomas to endocrine therapy.

As previously reported, ovarian epithelial carcinomas may respond to endocrine therapy. We examined the direct effect of progesterone, medroxyprogesteroneacetate, gestoneron, 17-beta-estradiol, tamoxifen, 4-OH-tamoxifen, or N-desmethyltamoxifen on the proliferative capacity of ovarian carcinoma cells by means of the colony assay described by Hamburger and Salmon. The growth rate of 25 tested tumors (ascitic fluid, primary tumor, metastases) was 68%. The plating efficiency was 0.078%. Beside the drug testing estrogen and progesterone receptor levels were determined. The inhibition of colony survival was slightest with 17-beta-estradiol, more pronounced with medroxyprogesteroneacetate, gestoneron, N-desmethyltamoxifen, and progesterone, and greatest with 4-OH-tamoxifen and tamoxifen. Significant and dose-dependent inhibition of greater than 70% was observed with tamoxifen and 4-OH-tamoxifen in 80% of the tested tumors. There was no significant correlation between the in vitro responsiveness and the level of hormonal act not only via an estrogen receptor but also via an antiestrogen-binding site.

Adenocarcinoma↗

Growth patterns and hormonal sensitivity of primary tumor, abdominal metastasis and ascitic fluid from human epithelial ovarian carcinomas in the tumor colony-forming assay.

The human tumor colony forming assay was used to evaluate the response of ovarian carcinoma cells from primary tumors, ascitic fluids and metastasis to hormonal treatment. In 12/35 patients a sufficient colony formation (greater than 30 colonies/dish) was obtained in order to perform a simultaneous drug testing. The plating efficiency of the metastatic samples (0.12%) was significantly higher (P less than 0.053) than those from the primary tumor (0.076%) or those that were derived from the ascitic fluid (0.082%). Colonies from the metastatic tissues could be evaluated 2-4 days earlier than those from primary tumors. These discrepancies may be due to a heterogeneity in the clonable tumor cell compartment of primary tumor and metastasis. The antiproliferative properties of the antiestrogen tamoxifen and the progestin gestoneron were studied. In 9/12 cases a significant, dose-dependent reduction of colony formation (greater than 70-90% of the controls) was observed after continuous exposure to 1 mumole tamoxifen. No correlation between the dose response and the content of steroid receptors was found. Even estrogen receptor negative tumor samples showed a maximal antiproliferative effect of tamoxifen.

Abdominal Neoplasms↗

[Significance of intraoperatively obtained peritoneal cytology in malignant ovarian tumors].

The evaluation of 259 peritoneal cytologic specimens obtained intraoperatively in cases of malignant ovarian tumor revealed positive findings in 62.5%; findings were doubtful in 2.3% and unusable in 2.7%. In the cases with clinically apparent peritoneal carcinomatosis, (n = 175), cytologic tests were positive in 75%. Taking tumor histology into account the high proportion of positive findings among the non-classifiable tumors (11 out of 13) was striking. For this reason, in a second investigation, 144 peritoneal cytologic specimens taken exclusively from cases of serous carcinomas were studied with regard to their degree of differentiation, the time of removal, and tumor spread. The peritoneal cytology was positive in 33% of the cases without peritoneal carcinomatosis at the first operation and in 36% of the cases with only histologically detectable tumor remnants at the time of the second-look operation. With one exception, peritoneal cytology was also negative in 26 second-look cases without clinically or histologically detected tumors. The incidence of positive peritoneal cytology findings was significantly higher in serous tumors with low-grade differentiation.

Ascitic Fluid↗

[Non-puerperal mastitis. Etiology, clinical aspects and therapy].

Non-puerperal mastitis was diagnosed in 79 patients (aged 12-77 years) over the years 1974-1984. Malignant neoplasm was not present. Bacterial infection in the region of the areola was the most frequent finding (40%), followed by abacterial inflammation without involvement of the nipples (29%). The other cases, bacterial or nonbacterial, occurred at different sites. The histological picture or clinical features of an increased secretory activity of the mammary gland (galactorrhoea, mastodynia) in addition to the mastitis was noted in 54 women. Causative organisms were proven in 53% of cases: Staph. aureus (41%) and coagulase-negative staphylococcus (41%), or anaerobic organisms (11%). Physical measures, antibiotics and bromocriptine were used as treatment. At the onset of treatment abscesses were already present or developed in 34 instances. In 28 cases one to six recurrences set in after the end of the treatment period. In 22 patients treated with bromocriptine prophylactically there were only two recurrences. In the majority of patients an increased alveolar secretion was important in the pathogenesis of the bacterial or abacterial inflammation. Prolactin-lowering treatment seems reasonable by itself in cases of abacterial mastitis, or in combination with antibiotics in bacterial mastitis. Recurrences can be prevented by long-term lowering of the peripheral prolactin level.

Adolescent↗

Cloning ovarian carcinoma cells in an agar double layer versus a methylcellulose monolayer system. A comparison of two methods.

Human ovarian cancer cells from ten patients were cultured in the agar double layer assay as described by Hamburger and Salmon and in a methylcellulose monolayer system. The assays were compared under the same experimental conditions. The rate of positives (defined as greater than 30 colonies/dish) was 75% in the methylcellulose assay and 69% in the agar double layer. Plating efficiency ranged in the methylcellulose assay between 0.021% and 0.089% and in the agar double layer from 0.015% to 0.094%. Cytological and cytochemical staining of cells obtained from colonies in both test systems and of the tumour cells prior to plating revealed the same morphology. The methylcellulose monolayer system requires less additives than necessary in the agar double layer system. Furthermore, it is easier to handle with respect to the plating procedure and less time consuming. In addition, the effect of the anti-oestrogen tamoxifen on colony formation was tested. The dose response curves for colony formation with tamoxifen proved to be identical in both systems. At a concentration of 10(-6) M an inhibition of colony formation of more than 70% of controls was observed in the agar and in the methylcellulose system.

Agar↗

[Control of the response of ovarian cancers to cytostatic therapy and the value of the second-look operation].

The importance of a second-look operation (SLO) in 121 patients with ovarian carcinoma stages III and IV from 1979 to 1983 is forthwith discussed. This operation was carried out in 58% of the patients. If no tumor was suspected after chemotherapy (n = 33), this only applied in 19 cases after a SLO. Of the patients in partial remission the preoperative diagnosis was correct in 14 of 21 cases and in no change 4 of 9 cases. Clinically the progress was always diagnosed reliably. Additional removal of residual tumors was successful in 7 of 49 cases (14%). This is only possible in small quantities of residual tumor. An improvement in the prognosis did not occur. Predictions on the right time to carry out a SLO and the purpose of a secondary tumor resection cannot be made.

Antineoplastic Combined Chemotherapy Protocols↗

Prognostic relevance of ploidy, proliferation, and resistance-predictive tests in ovarian carcinoma.

In a cooperative study specimens of 37 patients with stage III and IV ovarian carcinomas who had been treated with chemotherapy were investigated utilizing flow cytometry and an in vitro short-term test for predicting resistance. Patients with aneuploid tumors had significantly shorter survival rates than did those with diploid tumors. Patients whose tumors showed a low G0/G1 cell proportion or a high proliferation pool (S- and G2/M cell-proportion) seemed to die earlier. There was also a tendency for patients with in vitro resistant tumors to die earlier under chemotherapy than those with sensitive tumors.

Adult↗

Diagnosis and staging of ovarian cancer.

The diagnostic process in ovarian carcinoma is divided into the pre- and intraoperative procedures, examinations of tumor tissue, and follow-up. For preoperative diagnosis, the probability of a palpable adnexal mass being a malignant tumor should first be ascertained by sonography. This should be followed by an appropriate general examination, a search for tumor outside the abdominal cavity and in the liver parenchyma as well as by determination of markers. Intraoperative diagnosis determines the tumor stage and must be carried out all the more comprehensively when the ovarian carcinoma is more limited. Histologic subtype and degree of differentiation are in direct relation to the tumor stage, whereas the size of the primary tumor is often indirectly proportional to its extent. Besides the morphological analysis, the determination of possible chemoresistance and chemosensitivity, as well as further investigations on fresh tumor tissue are included in the tissue examination. Follow-up after a curative operation consists of gynecologic examination and Douglas lavages if tumor is still present in CT Scans and sonographs. To verify a relapse, laparoscopy can be used, but to ascertain a complete remission, a laparotomy is necessary.

Animals↗

[Steroid hormone receptors in ovarian carcinomas and their clinical significance].

Concentrations of estrogen (ER) and progesterone receptors (PR) were determined in 197 malignant tumors of the ovary. The frequency of receptors was the same as in breast cancer (ER 64%, PR 49%). In non-epithelial ovarian carcinomas steroid receptors were found only in granulosa cell tumors. PR was found less often in metastases than in primary tumors and after chemotherapy. Premenopausal tumors were more often PR-positive than postmenopausal carcinomas (71% versus 52%). ER were always constant. PR-negative tumors seemed to respond better to chemotherapy than positive tumors. Patients with PR-negative ovarian carcinomas seem to have a better prognosis than patients with PR-positive cancer. The clinical stage or the histological grade of the tumors did not correlate to the receptor status.

Adult↗

[Estrogen and progesterone receptors in malignant ovarian neoplasms].

Estrogen receptors (ER) and progesterone receptors (PR) were evaluated in 173 primary ovarian cancers and in 6 ovarian metastases. In epithelial ovarian carcinomas 63% had ER and 46% PR. Almost all granulosa cell tumours were receptor-positive, while sarcomas, dysgerminomas, and teratomas lacked ER and PR. Both receptors were found less often in tumours of the histological grade I than in those of grade II and III. During the development of metastases and during chemotherapy there was a loss of PR in 27% and 53% of the cases, respectively, while the amount of ER remained more or less constant. In addition to ovarian cancers ER and PR were present in carcinomas of the fallopian tube as well. ER-negative and especially PR-negative tumours seemed to respond better to chemotherapy than receptor-positive carcinomas. The possible significance of ER and PR with regard to the success of an endocrine treatment is discussed.

Carcinoma↗

Chemotherapy for stage III-IV ovarian cancer: the CAP-regimen in previously untreated patients.

Twenty-nine patients with advanced previously untreated epithelial ovarian cancer (FIGO stage III + IV) received induction chemotherapy with CAP (cyclophosphamide 500 mg/m2, adriamycin 50 mg/m2 and cis-platinum 50 mg/m2). Of twenty patients whose post-surgical tumor size was greater than 2 cm, fifteen (75%) achieved objective response. The median duration of complete response is greater than 20 months and the median duration of partial response is greater than 11 months. Among the 75% responders (15 of 20) overall, eleven were determined by surgical evaluation and four by clinical evaluation. The response rate in the present study compares favorably with previously reported studies. Toxicity from the CAP regimen was frequent and often severe but no irreversible side effects or treatment related deaths were observed. It is concluded that the CAP regimen appears to be an effective drug combination against advanced ovarian cancer that may improve overall response and ultimate survival of previously untreated patients.

Adult↗

The importance of gestagen, tamoxifen and steroid receptors in the therapy of endometrial cancer. Report of an experiment.

Six human endometrial cancers in different clinical stages were xenotransplanted into thymusaplastic nude mice. Estrogen and progesterone receptors in the tumor tissue were determined in each case. Two carcinomas with both estrogen and progesterone receptors showed a better clinical course and grew more slowly in nude mice than the four carcinomas with no receptors at all. Treatment with the antiestrogen Tamoxifen in the carcinoma with positive estrogen receptors showed a significant growth retardation compared with the control group. Estrogen treatment gave accelerated growth, whereas gestagen treatment showed no significant effect. The progesterone receptor content of the receptor-positive tumor tissue might have been too small. None of the four receptor-negative carcinomas showed any influence of tumor growth during endocrine therapy. The results demonstrate the importance of receptor determination as a prognostic sign and, further, allow the endocrine therapy of endometrial carcinomas to be complemented with Tamoxifen in estrogen-receptor-positive tumor tissue.

Aged↗