Alterations of the Birt-Hogg-Dubé gene (BHD) in sporadic colorectal tumours.
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Base Sequence↗
Biomedical subjects
E Segelov
Publications and source records attributed to E Segelov.
Mechanisms determining sensitivity to cisplatin in three mutant Chinese hamster ovary cell lines.
To gain insight into factors determining the response of tumours to cisplatin, we studied pathways involved in resistance to cisplatin: drug uptake, cytoplasmic detoxification and DNA repair, in three cisplatin-sensitive Chinese hamster ovary (CHO)2 mutant cell lines. The mutant lines, CHO-MMC6, CHO-MMC1, CHO-MMS2, displayed inherent sensitivity to cisplatin (2.2, 4.1 and 10.6-fold, respectively) compared to the CHO-K1 line from which they were derived. CHO-MMS2 was the only mutant to show sensitivity to UV and this was slight (< 2-fold). None of the mutants displayed increased sensitivity to X-irradiation. The CHO-MMS2 cell line appeared to have multiple mechanisms involved in its sensitivity to cisplatin, including increased drug accumulation, decreased levels of glutathione and a decreased capacity for DNA repair. The CHO-MMC1 mutant demonstrated reduced ability for DNA repair in a host cell reactivation assay, but no difference in drug accumulation or glutathione levels compared to the parent. The CHO-MMC6 cell line was not defective in any of the mechanisms studied. These three mutant cell lines demonstrate that similar mechanisms may account for inherent sensitivity or resistance to cisplatin, and suggest that multiple mechanisms may determine the sensitivity of human tumours to cisplatin.
Animals↗
Long term response to chemotherapy in patients with visceral metastatic melanoma.
PATIENTS AND METHODS: Eight patients who remain in long term remission 4 to 15 years after chemotherapy for visceral metastatic melanoma are described. These patients were observed among some 1100 patients with visceral melanoma seen at the Sydney Melanoma Unit between 1977 and 1989. Only about one-third of such patients received chemotherapy, almost always with single agent dacarbazine or a nitrosourea. RESULTS: The apparently cured patients did not differ from the overall group of patients with visceral metastases in baseline characteristics, but 6 of the 8 had nodular lung metastases. CONCLUSIONS: While the mechanism remains uncertain, one possibility could be that chemotherapeutic agents cause mutations which allow expression of antigenicity in tumour cells. In any case, the fact of occasional exceptionally good responses, perhaps amounting to cure, constitutes an argument for a trial of chemotherapy in patients with visceral metastatic melanoma.
Adolescent↗
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↗
A phase II study of carboplatin and cisplatin in advanced ovarian cancer.
In view of the single agent activity of both cisplatin and carboplatin in epithelial ovarian cancer, and their different toxicity profiles, we carried out a phase II study of low dose cisplatin (50 mg/m2) in combination with moderate dose carboplatin (300 mg/m2) in patients with advanced ovarian cancer. Fourteen patients, all of whom had bulky disease and over half of whom had Stage IV disease, were eligible for assessment of response and toxicity. An overall response rate of 71% was demonstrated (57% complete response, 14% partial response), which is at least equivalent to other regimens used in first line treatment of ovarian cancer. Toxicities encountered were nausea/vomiting and myelosuppression, however no serious renal neuro or ototoxicity was observed and the regimen does not cause significant alopecia. This combination may be a practical alternative to regimens which use high dose cisplatin to achieve similar efficacy.
Aged↗
Acute leukaemia following chemotherapy including etoposide for testicular carcinoma.
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Adult↗
The impact of histological review on clinical management of testicular cancer.
Accurate histological diagnosis and staging are critically important in determining the optimal management of patients with testicular cancer. We have assessed the importance of histological review of "outside" pathology reports from 87 patients referred to the Urological Cancer Research Unit. In 28 patients (32%), the reviewed pathology report differed from the outside report. In 10 of these patients (11%), the pathology review resulted in a change of treatment or prognosis from that which would have obtained in the absence of such histological review. Pathology review at a major cancer centre with a subspecialist interest in tumour pathology and a large experience in the management of germ cell malignancy is an essential first step in the treatment of testicular cancer.
Adult↗
Redressing the balance--the ethics of not entering an eligible patient on a randomised clinical trial.
A double standard exists whereby a treatment given outside a clinical trial is less stringently reviewed than a protocol treatment. We propose a remedy which would require the decision not to participate in an approved, available clinical trial to be subject to the same ethical requirements as trial entry.
Attitude of Health Personnel↗
Risk factors, epidemiology, screening, and prognostic factors in female genital cancer.
This review, which due to limitations of space cannot be exhaustive, summarizes the recent literature on risk factors and epidemiology, screening and prognostic factors in a cervical, ovarian, and endometrial cancer. There have been a large number of pertinent publications during this period and this paper summarizes and highlights recent advances in the identification of women at particularly high risk of developing gynecologic cancer, analyzes studies on early detection and screening, and reviews prognostic studies with particular reference to selection of therapy according to risk of relapse and likelihood of benefit.
Female↗
Metastatic melanoma presenting at diagnosis as a testicular mass.
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Adult↗