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M L Friedlander

Publications and source records attributed to M L Friedlander.

At least 37 records · Page 2Linked to original sources
PubMed1995

Uterine papillary serous carcinoma. A clinical study.

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a histologic subtype of endometrial adenocarcinoma that is characterized by its papillary architecture, poor differentiation, and advanced stage at initial presentation. It behaves more aggressively than the more common endometrioid adenocarcinoma of the endometrium. METHODS: The history, treatment and follow-up of 18 women with UPSC were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingoophorectomy. Positive lymph nodes were found in 6 of 14 patients who underwent pelvic lymphadenectomy. Twelve of 18 women with UPSC had FIGO Stage III and IV tumors in contrast to 30 of 236 patients with endometrioid adenocarcinoma (P < 000.1). Subsequent treatment of these women was: radiotherapy, three women; chemotherapy, four, both radiotherapy and chemotherapy, eight. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. None of the patients with Stage I or II UPSC died of tumor during a mean follow-up of 31.6 months (range, 12-68 months). Of the women with Stage III and IV disease, 4 of 12 are alive with no evidence of disease after a mean follow-up of 22.5 months (range, 8-45 months). Eight of 12 women who received chemotherapy are alive with no evidence of disease, 4 of whom had Stage III or IV disease. One of six women who did not receive chemotherapy is alive, three died of tumor, and two of intercurrent disease. CONCLUSION: These results would justify further study of the possible role of platinum-based chemotherapy in patients with uterine papillary serous carcinoma.

Aged↗
PubMed1994

Cisplatin-based chemotherapy for ovarian germ cell malignancies: the Australian experience.

PURPOSE: This study was performed to evaluate the Australian experience with cisplatin-based treatment of ovarian germ cell tumors (OGCT) with respect to survival and toxicity of treatment. PATIENTS AND METHODS: A retrospective review was undertaken based on a standardized questionnaire, which was sent to all major gynecologic oncology centers in Australia. RESULTS: Data on 58 patients were obtained. Overall survival at 5 years for all patients was 87%. There was one death from disease among 14 patients with dysgerminoma, and four deaths from disease among 44 patients with nondysgerminomas. Cisplatin-based chemotherapy was associated with a low incidence of serious complications, with only one treatment-related death (from bleomycin-induced respiratory failure). CONCLUSION: Our large series demonstrates that cisplatin-based chemotherapy is highly effective for patients with OGCT. Although direct comparisons cannot be made, the survival of our patients with advanced tumors was comparable to that seen in male germ cell tumors, rather than inferior as is commonly believed. Future studies should aim to refine treatment to minimize toxicity, while further increasing curability.

Adolescent↗
PubMed1992

Amplification of HER-2/neu oncogene in human ovarian cancer.

Amplification and/or increased expression of the HER-2/neu oncogene has been reported to occur in ovarian tumors and possibly to correlate with biologic behavior and prognosis. The frequency with which amplification is reported to occur is quite variable ranging from 0-30% in different series and this variability is probably accounted for by technical and methodologic factors. The variability and lack of reproducibility has raised questions about the usefulness of assessing amplification of the HER-2/neu oncogene and in particular its clinical relevance. In this study by using strict criteria for amplification and using multiple controls we could demonstrate unequivocal amplification of the HER-2/neu oncogene by Southern blot analysis in only 11% of malignant ovarian tumors. The potential pitfalls with the techniques used to detect HER-2/neu oncogene amplification and overexpression are reviewed and possible ways to overcome some of the problems are suggested.

Journal Article↗
PubMed1992

Prognostic factors in ovarian cancer.

Epithelial ovarian cancers vary considerably in their biologic behavior and this is reflected in the variety of clinicopathologic factors that are used for predicting outcome. This article assesses the potential value of some of the newer prognostic factors and critically evaluates the more commonly used clinicopathologic variables.

Female↗
PubMed1990

Demonstration of somatic rearrangements and genomic heterogeneity in human ovarian cancer by DNA fingerprinting.

A detailed study was performed in 14 patients with epithelial ovarian tumours using the satellite probes 33.15, 228S and 216S to investigate the nature of somatic changes and frequency with which clonal changes could be demonstrated during metastasis and progression. Somatic changes were evident in approximately 70% of ovarian tumours, the most common being a deletion or reduction in intensity of a band suggesting loss of heterozygosity. Additional changes that were observed included increased intensification of single bands and the appearance of novel DNA fragments. Somatic alterations were seen following digestion of DNA with methylation resistant restriction endonucleases indicating that methylation differences alone could not account for all of the somatic changes. Using DNA fingerprint analysis ovarian tumours were shown to be heterogeneous with different DNA patterns observed in different sites in five of eight patients. Generally, within an individual patient the primary and metastases appeared to share a DNA fingerprint pattern with minor variations occurring in different sites suggesting that different populations have derived from a common stem line. This study clearly demonstrates that DNA fingerprint analysis is a sensitive method to detect somatic changes in tumour DNA and for investigating the development of clonal heterogeneity in ovarian tumours.

Adenocarcinoma↗
PubMed1989

Amplification of c-ras-Ki oncogene in human ovarian tumours.

Amplification of the c-ras-Ki oncogene has been the most consistent finding reported in studies on oncogene activation in ovarian cancer, but for the most part the studies have been small and the results conflicting. In order to determine whether amplification occurred de novo in primary tumours or was associated with tumour progression and metastasis, 81 tumour samples from different sites in 26 patients with ovarian tumours and 7 xenografted ovarian tumour cell lines were assayed. Amplification of c-ras-Ki occurred infrequently and was apparent in a single metastatic site in a patient with poorly differentiated serous cystadenocarcinoma of the ovary. Ten-fold amplification of the c-ras-Ki oncogene was also evident in a benign ovarian fibroma. Amplification of the c-ras-Ki oncogene is rare in ovarian tumours and does not appear to play a fundamental role in tumor development or progression.

Blotting, Southern↗
PubMed1989

A phase I study of trimetrexate (NSC 352122) administered by 5-day continuous intravenous infusion.

Trimetrexate (TMTX) is a potent inhibitor of dihydrofolate reductase that circumvents the transport resistance seen with methotrexate and has a wide spectrum of preclinical activity. A total of 18 patients with advanced cancer were treated in a clinical and pharmacological phase I trial with TMTX given as a continuous 5-day intravenous infusion. Neutropenia, thrombocytopenia and stomatitis were the dose-limiting toxicities at the maximum tolerated dose of 50 mg/m2 per 120 h (10 mg/m2 per day for 5 days). There was one septic death associated with neutropenia. Other toxicities were mild rash, mild nausea and transiently raised serum transminase levels. Significant relationships between the dose given and the AUC of plasma TMTX and the steady-state plasma level were established. Significant, although weak, relationships between the percentage of change in neutrophils and platelets and both the AUC and steady-state plasma level of TMTX were also observed. No objective tumour responses were seen, although six patients had stable disease. The recommended phase II dose for a continuous infusion of trimetrexate is 40 mg/m2 per 120 h.

Adult↗
PubMed1989

The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors.

Tumor specimens from 92 patients with ovarian carcinoma were analyzed for estrogen receptor (ER), progesterone receptor (PR), proliferative fraction, and ploidy. Seventy-one percent of tumors were either ER+ (greater than 5 fmole/mg protein) or PR+ (greater than 10 fmole/mg protein) with 27% of tumors overall being both ER+ and PR+. There was no significant relationship between receptor expression and stage, grade, or histological subtype. Thirteen percent of diploid tumors were receptor negative in contrast to 38% of aneuploid tumors (P less than 0.01). There was no significant association between ER status and ploidy, but 60% of diploid tumors were PR+ in contrast to 33% of aneuploid tumors (P less than 0.02). Eleven percent of tumors overall were both ER rich and PR rich and comprised 23% of diploid and 5% of aneuploid tumors (P less than 0.01). Receptor-negative tumors had a median S phase of 18.8% which was significantly higher than the median S phase of 12% in receptor-positive tumors (P less than 0.02). A similar analysis was also performed on specimens from 9 patients with borderline epithelial ovarian tumors and 12 with benign epithelial ovarian tumors. Up to 50% of benign and borderline epithelial tumors had measurable receptors, but all were diploid with a relatively low S phase fraction. The functional significance of steroid receptor expression in ovarian cancer is unclear, but the association with ploidy and proliferative activity particularly in patients with malignant ovarian tumors may allow better identification of prognostic subsets and aid in selection of patients for hormonal therapy.

Adult↗
PubMed1989

Comparison of western blot analysis and immunocytochemical detection of P-glycoprotein in multidrug resistant cells.

A sensitive immunocytochemical technique was developed to detect a 170,000 dalton cell membrane glycoprotein (P-gp) in cell lines resistant to vincristine and vinblastine with varying degrees of resistance. P-gp was shown very clearly using the C219 monoclonal antibody and immunocytochemical detection with either antialkaline phosphate or peroxidase-antiperoxidase with silver gold intensification. There was good correlation between the results obtained with immunocytochemical detection of P-gp in single cells and Western blot analysis. The technique is easily performed and can detect P-gp in relatively small numbers of cells that Western blot analysis could miss and is suitable for clinical application.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Alpha-monoamides of methotrexate as potential prodrugs.

alpha-Monoamides of methotrexate were evaluated for their potential as prodrugs. Studies on 11 alpha-monoamides and 5 gamma-monoamides of methotrexate showed that the gamma-monoamides were about as strong inhibitors of Lactobacillus casei dihydrofolate reductase as methotrexate, while I50 of the alpha-monoamides were 1-2 orders higher. The concentration for growth inhibition of murine L1210 cells for methotrexate gamma-propylamide and alpha-propylamide were respectively 1-2 and 2-3 orders higher than that of methotrexate. In contrast, only alpha-monoamides caused significant increase in life span of mice with transplanted L1210 leukaemia, the highest effect being given by the alpha-propyl and the alpha-butylamide. The possibility that the in vivo activity of the alpha-monoamides might be related to in vivo transformation to methotrexate was studied by HPLC analysis of mice serum after administration of the alpha- and gamma-propylamides.

Animals↗
PubMed1988

Ovarian carcinoma: abdominopelvic irradiation following reexploration.

Twenty patients with ovarian cancer, who following reexploration were left with residual disease nodules of less than 2 cm diameter, received abdominopelvic irradiation. Of these patients 18 had previous chemotherapy. Fifteen patients completed treatment, 13 of whom had prior chemotherapy. Six of the 18 patients with invasive tumors were alive and disease free 18-53 months postradiotherapy, while only 4 patients had died at the time of follow-up. No patient with residual nodules greater than 1 cm remained disease free. There was no difference in outcome between patients with microscopic or macroscopic less than 1 cm residuum. Complications were acceptable with 3/20 (15%) developing treatment-related intestinal obstruction.

Adenocarcinoma↗
PubMed1988

Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer.

The prognostic value of cellular DNA content in ovarian cancer (malignant common epithelial tumors) was investigated by flow cytometric analysis of paraffin-embedded tumor blocks from 128 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian cancer entered in a prospective clinical trial of combination v sequential therapy with chlorambucil and cisplatin. Seventy-three percent of tumors were aneuploid and 27% were diploid. Multivariate analysis using a Cox model showed that cellular DNA content (P less than .001) and FIGO stage (P less than .02) were the only significant independent prognostic variables. The median survival was 13 months for patients with aneuploid tumors and 60 months for patients with diploid tumors (P less than .0001). Further analysis indicated that the good prognosis associated with diploid tumors was limited to patients with stage III disease, all patients with stage IV (spread beyond the peritoneal cavity or liver metastases) disease having a poor prognosis irrespective of ploidy. On pathological review, nine borderline ovarian tumors (of low malignant potential) were identified, and seven of these were diploid. These tumors have an unusually favorable prognosis, despite apparent dissemination within the peritoneal cavity, a paradox which is often difficult to explain using conventional histological criteria. Although the vast majority of tumors in this study (93%) were classified as invasive epithelial ovarian cancers, it is possible that some of the patients with stage III diploid tumors may have had malignancies that were predominantly of low malignant potential, thus accounting in part for the prognostic significance of DNA content. By incorporating flow cytometric DNA analysis with careful histopathological assessment, it may be possible to better identify patients with an inherently good prognosis. This assumes particular importance, as the relatively favorable prognosis of patients with stage III diploid ovarian tumors appears to be independent of the type of treatment.

Antineoplastic Combined Chemotherapy Protocols↗