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Biomedical subjects

M H Tattersall

Publications and source records attributed to M H Tattersall.

At least 109 records · Page 6Linked to original sources
PubMed1990

Achievable goals and relevant endpoints in cancer treatment.

The goals of cancer treatment range from eliminating cancer to prolonging the time to recurrence, controlling local disease, and palliating symptoms. For many cancer patients, disease elimination is an unrealistic treatment goal at the time of diagnosis due to the presence of metastatic disease and the lack of effective systemic treatment. For other patients, treatment options with similar survival expectation but differing side effects may complicate treatment selection. There is a clear need for new cancer treatment endpoints to be developed so that the effects of cancer treatment may be appropriately monitored. Some recently developed cancer treatment endpoints are described, and their use in clinical trials is advocated.

Combined Modality Therapy↗
PubMed1989

Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases.

The rate and clinical features of patients admitted to King George V Hospital with extraovarian peritoneal serous papillary carcinoma during a 9-year period were reviewed. In this time, 31 of 236 (13%) patients with an initial diagnosis of invasive serous ovarian carcinoma fulfilled the surgicopathologic criteria for this entity. All patients had disseminated tumor equivalent to ovarian Stage III and IV disease (International Federation of Gynecology and Obstetrics [FIGO]) and with predominantly high-grade neoplasms. They were managed by surgical exploration, tumor debulking where possible, and postoperative chemotherapy. A comparison with a contemporaneous series of 139 patients with primary epithelial ovarian carcinoma matched for stage and grade of disease and managed similarly showed no difference in actuarial survival. The median survival times were 11.3 months for patients with extraovarian serous papillary carcinomas and 13.5 months for patients with equivalent primary ovarian neoplasms. The features of the disease and the treatment regimens used are discussed.

Adult↗
PubMed1989

Elevated apolipoprotein(a) levels in cancer patients.

Elevated plasma lipoprotein(a) has been associated with an increased risk of cardiovascular disease. We report a significant elevation of total plasma apolipoprotein(a) levels in cancer patients compared with hospitalized control patients and normal healthy blood donors. Of the cancer patients studied, 48% had levels in excess of 350 mg/l compared to 20% in normal blood donors and 29% of hospitalized control patients. The elevation was more prevalent but less extreme than that reported in patients with cardiovascular disease. Density gradient centrifugation studies of plasma from cancer patients revealed the presence of apolipoprotein(a) at a density of 1.085 g/ml in the region where mRNA-containing proteolipids, neoproteolipids and malignancy-associated lipoproteins had previously been isolated.

Apolipoproteins A↗
PubMed1989

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.

Adult↗
PubMed1989

Enumeration of 6-thioguanine-resistant tumour cells using flow cytometry and comparison with a microtitration cloning assay.

Measurement of mutant frequency in tumour specimens has been hampered by low cloning efficiency in soft agar. A method was developed to detect cell proliferation using the thymidine analogue 5-bromo-2'-deoxyuridine (BrUdR). BrUdR incorporation was monitored by immunofluorescent staining of fixed cells using a monoclonal antibody highly specific for this nucleoside analogue. The 6-thioguanine (6TG) exposure conditions which inhibited DNA synthesis, as measured by BrUdR incorporation, in wild-type cells while allowing proliferation of spontaneous hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutants were investigated using tumour cell lines. It was shown that exposure to 10(-5) M BrUdR for the equivalent of 1 cell cycle time did not affect growth of wild-type cells, nor did it affect the growth of HPRT- mutants in the presence of 6TG. Methods for rapid flow cytometric enumeration of BrUdR-labelled 6TG-resistant cells were developed using fluorescent microspheres as an internal standard. To validate the BrUdR mutation assay, the 6TG mutant frequency (MF) was measured in L1210 R/S, a mouse leukaemic cell line (BrUdR 6TG MF = 7.0 X 10(-5] and the results directly compared with those from a microtitration cloning assay (MF = 4.6 X 10(-5]. The results were similar and within the range reported for HPRT MF in mammalian cells.

Animals↗
PubMed1989

Potentiation of methotrexate lymphocytotoxicity in vitro by inhibitors of nucleoside transport.

Modulation of nucleic acid antimetabolite cytotoxicity by preformed purines and pyrimidines may not only complicate the interpretation of drug sensitivity tests and other in vitro studies but also adversely affect treatment in vivo. Previously we reported that in a lymphocyte clonal assay, thymidine and hypoxanthine released from dead or damaged cells reduced methotrexate cytotoxicity. We now report that the nucleoside transport inhibitor dipyridamole (DP), at 1.0 microM, abolished 3H-thymidine uptake into PHA stimulated lymphocytes, potentiated methotrexate cytotoxicity and reversed modulation of methotrexate cytotoxicity by exogenous thymidine and hypoxanthine. Normal growth of lymphocytes at high density was unaffected by 1.0-5.0 microM dipyridamole, while growth at low densities was only slightly reduced. Hydroxy-nitrobenzylthioguanosine (555) was a less potent inhibitor of 3H-thymidine uptake and was toxic to normal lymphocytes at concentrations inhibiting 3H-thymidine uptake. Nucleoside transport inhibitors isolate the cellular effects of nucleic acid antimetabolites, and provide a tool to study mechanisms of antifolate cytotoxicity.

Cell Survival↗
PubMed1989

Primary cerebral lymphoma: presentation of eight cases and review of the literature.

Eight cases of primary cerebral lymphoma (PCL) are presented, being the largest Australian series of this rare condition reported to date. The clinical, radiological, anatomical and histological features were found to be comparable with those of patients reported in other series between 1954 to 1986. The precise treatment of PCL remains undetermined due to its rarity and apparent heterogeneity. Whole brain irradiation forms the basis of therapy although the role of prophylactic spinal irradiation, surgery and chemotherapy have not been defined. Response to corticosteroids and chemotherapy has been documented. Reported cases associated with the acquired immune deficiency syndrome (AIDS) are discussed. With an anticipated increase in the number of cases of AIDS, the incidence of related PCL will also increase. Large, multicentric trails are required to further delineate optimal treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunohistochemical determination of tumour growth fraction in human ovarian carcinoma.

The proportion of proliferating tumour cells in a tumour ('growth fraction') was estimated in 30 patients with primary ovarian carcinoma, using monoclonal antibody Ki-67 which reacts with a nuclear antigen present only in proliferating cells. A positive correlation between the 'growth fraction' and both the clinical stage and histological grade of the tumours was observed. A high 'growth fraction' was observed in advanced, metastatic and poorly differentiated tumours and a low 'growth fraction' with early stage, well-differentiated tumours. This information which has not been available previously to clinicians may be of practical value for determining the prognosis, and influencing treatment recommendation.

Antibodies, Monoclonal↗
PubMed1989

Method of extracting DNA from fine needle aspirates of human solid tumors for Southern blot analysis.

A rapid, simple, convenient method for extracting DNA from fine needle aspiration (FNA) samples of human solid tumors for Southern blot hybridization studies is described. After the preparation of an air-dried cytologic smear, the remaining sample in the needle was rinsed directly into a test tube for DNA extraction. The extraction procedure, in which manipulation of the sample is minimized, produced sufficient DNA for Southern blot analysis within 24 hours of the FNA biopsy in the ten consecutive cases studied. The DNA bound to the nylon membranes can be washed and reexamined with a variety of probes, allowing studies of lymphoid cell lineage, oncogene amplification or tumor progression. The assessment of cellularity on the cytologic specimen at the time of FNA provided a reliable guide to the need for further passes to obtain sufficient cells for DNA hybridization; the cytologic diagnosis could also be made on the smears.

Adenocarcinoma↗
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

Flow cytometric enumeration of drug-resistant tumor cells.

In an attempt to elucidate the role of somatic mutation in the development of resistance to cancer chemotherapy, an assay was sought to measure the frequency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutants in human tumors. Based on the same principle as [3H]thymidine/autoradiography, a method was developed to identify cell proliferation using the thymidine analog 5-bromo-2'-deoxyuridine (BrdUrd). BrdUrd incorporation into DNA was measured following the immunofluorescent staining of fixed cells using a monoclonal antibody highly specific for this nucleoside analog. The human leukemic cell line, CCRF-CEM, was used to investigate the conditions necessary for the stringent selection of HPRT- mutants using 6-thioguanine (6TG). The appropriate 6TG exposure necessary to inhibit BrdUrd incorporation in wild-type cells, while allowing proliferation of spontaneous HPRT- mutants, was greater than or equal to 30 microM 6TG for 72 h (10 microM BrdUrd added 24 h prior to harvest). BrdUrd did not affect the growth of HPRT- mutants in the presence of 6TG. BrdUrd-labeled 6TG-resistant cells were enumerated flow cytometrically using fluorescent microspheres as an internal standard and the nonparametric, Kolmogorov-Smirnov test was used for independent statistical analysis of the subpopulations of fluorescent, 6TG-resistant cells. Evidence that CCRF-CEM cells which incorporated BrdUrd in the presence of 6TG were, in fact, HPRT- mutants was sought. It was demonstrated that spontaneous 6TG-resistant cells from the CCRF-CEM population were reduced by growth in medium containing aminopterin. The mutant frequency in the CCRF-CEM cell line was found to be 4.28 x 10(-5) +/- 2.04 x 10(-5) using the BrdUrd/flow cytometric technique.

Bromodeoxyuridine↗
PubMed1988

Chemotherapy of advanced head and neck cancer: updated results of a randomized trial of the order of administration of sequential methotrexate and 5-fluorouracil.

One hundred and twenty-seven patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNC) were randomized to treatment with methotrexate (MTX) followed 1 hour later by 5-fluorouracil (5-FU) (sequence MF), or 5-fluorouracil followed after 1 hour by methotrexate (sequence FM). One hundred and seventeen patients were evaluable for response. There was no significant difference in response rates between the MF and FM sequences. Overall, 8 patients (6.8%) achieved complete response (CR) and 46 (39.3%) partial response (PR). In 95 previously untreated patients, the overall response rate (CR + PR) was 50%, compared with 31% for previously treated patients (P = 0.02). Survival duration significantly favored the FM sequence in univariate analyses (P = 0.04). Stepwise multivariate Cox model analysis showed that poor performance status (Eastern Cooperative Oncology Group) at study entry (P less than 0.001) and prior radiotherapy (P = 0.03) were significant adverse predictors for survival. When allowance was made for these factors, a survival difference in favor of the FM sequence remained (P = 0.003). Sequential MTX followed 1 hour later by 5-FU is not recommended for treatment of HNC.

Antineoplastic Combined Chemotherapy Protocols↗