Search PubMed⌕ Search

Biomedical subjects

M H Tattersall

Publications and source records attributed to M H Tattersall.

At least 163 records · Page 9Linked to original sources
PubMed1985

Combined cyclophosphamide, adriamycin and cis-platinum in advanced ovarian cancer resistant to chlorambucil and cis-platinum.

Seventeen patients with advanced ovarian adenocarcinoma recurring or progressing after prior treatment with chlorambucil and cis-platinum were treated with cyclophosphamide, adriamycin, and cis-platinum (CAP) every 3 weeks. In seven patients there was objective tumor response (41%) with a median response duration of 7.6 months and a survival advantage over nonresponders. Patients whose tumors had previously responded to chlorambucil or cis-platinum were less likely to respond to CAP than those who had not responded. Myelosuppression was the main toxicity, febrile neutropenia occurring after 8% of treatments.

Adenocarcinoma↗
PubMed1985

Metastasizing placental site trophoblastic tumor: a case study.

The clinicopathologic features of placental site trophoblastic tumor (PSTT), a rare form of trophoblastic disease, were systematically described only relatively recently. Previously, in endometrial curettage and hysterectomy specimens, PSTT was not distinguished from choriocarcinoma or sarcoma, although in most cases the natural history had been benign. A case of biopsy-proved metastasis to para-aortic lymph nodes with radiologic evidence of lung metastasis is reported. Histologically, the tumor appeared similar to the tumors in other reported cases of PSTT. The mitotic rate was variable, being very high in a few small fragments obtained by curettage. Flow cytometric analysis of the tumor showed cells with diploid DNA content and a relatively low proliferative fraction. The tumor maintained its morphologic and functional characteristics following xenotransplantation into Balb/c nu/nu mice. In spite of a treatment regimen that included hysterectomy and multiagent chemotherapy, the patient continued to have evidence of persistent trophoblastic disease 15 months after presentation.

Adult↗
PubMed1985

Ovarian tumour xenografts in the study of the biology of human epithelial ovarian cancer.

Human epithelial ovarian tumours were successfully established as xenografts in nude mice in 54% of cases. An evaluation of the biological characteristics of tumours propagated in nude mice was carried out and the functions investigated included morphology, growth kinetics, cellular DNA content, cell surface antigen expression and sensitivity to chemotherapy. To allow a more detailed study of the influence of ploidy on biological behaviour, xenografted tumour with varying degrees of aneuploidy and tumours with a common ancestry but different ploidies were also established. Although this is a highly selective model system favouring the growth of biologically aggressive tumours the xenografts, in general, reflect many of the characteristics of the tumours from which they were derived and are likely to provide a useful model for investigating the biology of ovarian cancer.

Animals↗
PubMed1985

Multifocal tumorigenesis in the upper female genital tract--implications for staging and management.

A review of 128 cases of "primary" ovarian müllerian carcinoma treated at the King George V Memorial Hospital was undertaken to determine the relative frequency with which such tumors were associated with evidence of multifocal primary neoplasia. Of the 128 cases studied, 115 were invasive carcinomas and 13 were noninvasive or borderline ovarian tumors ("tumors of low malignant potential"). Eight of 10 borderline serous ovarian tumors (80%) and 37 of 75 invasive serous carcinomas (49%) exhibited evidence of independent primary neoplasia at more than one anatomical site in the biopsy material available for review. Many of these cases represented bilateral primary ovarian tumors, but autochthonous extraovarian neoplasia was also commonly encountered. A single borderline endometrioid ovarian tumor and six of 15 endometrioid carcinomas (40%) were associated with biopsy-proven multifocal primary tumorigenesis. These were predominantly neoplasms in one or both ovaries plus adenocarcinoma in the uterine corpus. Other histological types of malignant common epithelial tumors of the ovaries did not demonstrate any such tendency, highlighting major differences in pathogenesis between members of this loosely associated group of ovarian cancers. Our study suggests that gynecological endometrioid and serous malignancies are commonly multifocal and we feel this has significant implications for the way these neoplasms are staged and therefore treated.

Biopsy↗
PubMed1985

Cisplatin, vinblastine, and bleomycin in inoperable non-small cell lung cancer.

Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.

Adenocarcinoma↗
PubMed1985

A simple and rapid method for the identification of cycling cells in freshly excised tumours.

Cytogenetic studies of fresh solid tumours are hampered by the small numbers of poor quality metaphases which are obtained through direct preparations. The proportion of cycling cells in freshly excised tumours have been identified by measuring the incorporation of the nucleoside analogue 5-bromo-2'deoxyuridine (BrUdR) into DNA. We have developed an immunochemical method using a mouse monoclonal antibody directed against BrUdR which stains nuclei of cells which have incorporated this nucleoside. Using this method, optimal culture conditions and harvest times may be identified, to provide greater numbers of high quality metaphases, suitable for karyotyping solid tumours.

Antibodies, Monoclonal↗
PubMed1985

Selective toxicity of a new lipophilic antifolate, BW301U, for methotrexate-resistant cells with reduced drug uptake.

Three methotrexate (MTX)-resistant cell lines and their MTX-sensitive counterparts have been used to examine 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW301U), a novel lipophilic antifolate, and compare its cytotoxicity with MTX and metoprine. Collateral sensitivity for both BW301U and metoprine was observed in CCRF-CEM/MTX R-cells, where MTX resistance appeared to be primarily due to a deficiency in drug uptake. This was particularly pronounced with BW301U which proved to be as effective in killing CCRF-CEM/MTX R as was MTX with the parental CCRF-CEM cell line. This effect was not seen in other cell lines, L5178Y/MTX or L1210/MTX R, where resistance to MTX was correlated with either an overproduction of 5,6,7,8-tetrahydrofolate:nicotinamide adenine dinucleotide phosphate oxidoreductase EC 1.5.1.3 (DHFR) or with combined uptake defect and increased DHFR levels, respectively. In each case, however, BW301U and metoprine, especially at high concentrations, were more effective than MTX in treating MTX-resistant cells.

Antineoplastic Agents↗
PubMed1984

Treatment of advanced squamous-cell carcinoma of the head and neck with a combination of cisplatin, vinblastine, and bleomycin.

Fifty patients with advanced, measurable, squamous-cell cancers of the head and neck received treatment with a combination of cisplatin, vinblastine, and bleomycin (PVB). The tumours in 25 patients (50%) responded to treatment (partially in 17 and completely in eight). The median duration of response was 18 weeks, and that of survival was 31 weeks. Toxicity was moderately severe; myelotoxicity occurred in 13 patients, and nausea and vomiting in 22 patients.

Adolescent↗
PubMed1984

Dying of cancer. Factors influencing the place of death of patients.

An analysis of factors influencing the place of death of patients seen by two medical oncology units is reported. There were 1295 recorded deaths of patients from the Royal Prince Alfred Hospital, Sydney, and 688 from The Royal North Shore Hospital of Sydney during 1979-1981; the places of death were known in 1724 instances (87%). Of these, 73% of patients died in hospital, 9% died in terminal nursing care (TNC) institutions, and the remainder at home. Factors influencing the place of death were the place of residence, age, home circumstances-social support, diagnosis, and interval from first contact with the medical oncology unit. Our data indicate that a complex interrelation of these factors determines the place of death. Improvements in community services may allow more patients with cancer to die at home or in TNC institutions, but a substantial proportion of these will still die in major hospitals. Therefore, there is a need for the improvement of palliative care services in these institutions.

Adult↗
PubMed1984

The integration of chemotherapy into the management of locally advanced cervical cancer: a pilot study.

Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Cellular DNA content--a stable feature in epithelial ovarian cancer.

Detailed flow cytometric analysis of cellular DNA content was performed on neoplastic tissue from 33 patients with malignant common epithelial ovarian tumours in order to investigate the intratumoral stability of ploidy and proliferative fraction. There was a remarkable stability, both spatial and temporal, in the DNA pattern for any particular tumour. Of 24 tumours that were analysed in multiple areas tumour ploidy was found to be a stable marker in all but 3 cases where regional variations were evident. In 9 patients serial analyses were performed on tumour obtained either at initial diagnosis (6 patients) or second look laparotomy (3 patients) and then some time later (7-17 months) at relapse or death and in all cases the tumour ploidy remained unchanged. In addition, 10 ovarian carcinomas established in nude mice have maintained a DNA content during serial passage similar to that of the original implanted tumour. In contrast in 50% of tumours that were evaluable for S-phase analysis we demonstrated a considerable intratumoral variability in the S-phase fraction. We conclude that cellular DNA content is a stable feature of ovarian carcinoma while S-phase fraction is commonly subject to intratumoral variation.

Animals↗
PubMed1984

Advanced breast cancer: response to high dose oral medroxyprogesterone acetate.

We treated 105 patients with advanced breast cancer, using the progestational agent medroxyprogesterone acetate (MPA), 200 mg orally tds in a non-randomised trial. In general they were a poor risk population, since 78 had received prior endocrine therapy (21 more than one type) and 58 prior chemotherapy. Treatment was well tolerated. Side effects included weight gain, muscle cramps, fine tremor and fluid retention, but these were usually mild, resolved if the dose of drug was reduced, and only one patient stopped treatment because of toxicity. Seventeen patients died within six weeks of starting MPA, and disease progression occurred in a further 58. Nine have had stable disease for periods ranging from two to 11 months, and there were 21 who showed disease regression. Response to treatment continues in 13 of these patients, and at the time of writing the median duration of response is 10 months. Response rates were similar in pre- and post-menopausal patients. The dose of MPA was double to 400 mg tds in 16 patients whose disease had progressed on 200 mg tds, but no additional responses were seen in this group. Seven out of 24 (29%) patients who had not received prior endocrine therapy responded to high dose oral MPA, a response rate similar to that seen following other hormonal manipulations, but because the drug also has activity against hormone-resistant tumours and is well tolerated, it should have role in the treatment of advanced breast cancer.

Antineoplastic Agents↗
PubMed1984

Combination therapy with methotrexate and 5-fluorouracil: a prospective randomized clinical trial of order of administration.

Because of biochemical and tissue culture evidence casting doubt on the physiologic relevance of reported synergy afforded by sequential administration of methotrexate (MTX) followed by 5-fluorouracil (5-FU), a randomized controlled clinical trial was conducted in 108 patients with advanced cancer, including 70 with squamous cell carcinoma (SCC) of the head and neck, nine with SCC of other primary sites, 24 with colorectal, and five with gastric adenocarcinomas. Patients were randomized to receive weekly therapy consisting of MTX followed one hour later by 5-FU, or 5-FU followed one hour later by MTX. There was a trend to higher tumor response rates in patients treated with MTX before 5-FU (45% v 33% overall; 65% v 39% in patients with previously untreated head and neck cancer), but these differences were not significant, either by chi-square test or by multivariate stepwise logistic regression. The trend in survival favoring the reverse sequence of 5-FU before MTX was not significant in univariate analyses. Stepwise multivariate Cox model analysis showed that Eastern Cooperative Oncology Group performance status at study entry was the major prognostic factor for survival (P less than 0.001), but among the 70 patients with head and neck cancer, the sequence of drug administration was the only other significant prognostic factor for survival, and favored the sequence of 5-FU followed by MTX (P less than 0.025).

Adenocarcinoma↗
PubMed1984

Flow cytometric analysis of cellular DNA content as an adjunct to the diagnosis of ovarian tumours of borderline malignancy.

Flow cytometric analysis of cellular DNA content was performed on tissue from 44 borderline ovarian tumours (tumours of low malignant potential). Forty-two tumours (95%) were diploid and associated with both an indolent biological behaviour and good prognosis. Aneuploidy was identified in only 2 tumours (5%), and one of the associated patients died of progressive disease within months of the initial diagnosis. Careful review of the histopathology of these 2 aneuploid tumours revealed areas of invasion in the omental and peritoneal "implants" of each. This study has reinforced the currently advocated separation of so-called borderline tumours from invasive ovarian carcinomas and the interpretation of the pathological criteria used to categorize such neoplasms. Our results indicate that flow cytometric analysis of cellular DNA content may complement conventional histopathological diagnosis by providing an objective parameter which correlates with biological behaviour and may identify the few genuine borderline ovarian epithelial neoplasms which show clinical progression.

Adult↗