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Biomedical subjects

M H Tattersall

Publications and source records attributed to M H Tattersall.

At least 127 records · Page 7Linked to original sources
PubMed1988

Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer.

An increase in the plasma levels of apoprotein B-containing lipoproteins is the basis of the magnetic resonance (MR) test for cancer. The narrow MR line width reported by Fossel and co-workers to be associated with the presence of malignant disease is due to a relative increase of very low density lipoprotein. In contrast, the plasma from healthy controls, which has a much broader spectrum, has a higher proportion of high density lipoprotein. However, plasma from patients with hyperlipidemia unrelated to cancer also show narrow MR line widths and are therefore a confounding variable. We used magnetic resonance spectroscopy (MRS) to assess the plasma from 253 patients with a range of lipid related diseases and cancer, and 28 controls. A significant difference (p less than or equal to 0.0005) of 10 Hz exists between the mean line width of the controls and hyperlipidemics without malignant disease. However, in patients with solid tumours a difference of 7 Hz (p less than or equal to 0.0005) in the mean values is recorded although there is an overlap of 6 Hz compared with the controls. Moreover the MRS method was not found to distinguish patients with lymphomas from the control population. The index was not found to be related to patient age or tumour burden.

Adult↗
PubMed1988

Cisplatin plus VP 16-213 in advanced ovarian carcinoma.

Thirty-five patients with advanced epithelial ovarian carcinoma (24 untreated, 11 previously treated with alkylating agents) were treated with a combination of cisplatin and etoposide (VP16-213). Tumor response (i.e., complete response and partial response) was seen in 16 of the 35 patients (i.e., 46%), with 5 complete responses. The response rate in previously untreated patients was 54%, but only 27% in previously treated patients. The median survival was 42 weeks. The toxicity of this regimen was severe. Twelve patients became severely myelosuppressed, including one septic death while severely neutropenic. Treatment with cisplatin and etoposide produces only average tumor response rates and patient survival, but is associated with severe toxicity. There is no evidence of synergy between cisplatin and VP16 in this study.

Adult↗
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

Undergraduate education about cancer: a survey in Australian medical schools.

The goals of undergraduate medical education are to provide a core of basic knowledge, and a framework to permit further development of that knowledge. The structure of teaching and experience in cancer medicine should reflect the increasing importance of cancer in the community. Undergraduate teaching of oncology and its scientific bases is currently fragmented, and in some cases may be deficient. Until now, there have few analyses of what is being taught about cancer at different medical schools. We have undertaken a survey of final year medical students or recently qualified doctors in Australia enquiring about their cancer education. The results indicated that substantial differences existed between the medical schools, and we therefore surveyed the teaching faculty in the schools to determine their view of the validity of the questions we used. Together these surveys showed that significant disparities existed between what the faculty felt should be taught and what students had actually experienced.

Australia↗
PubMed1988

Modulation of antifolate cytotoxicity by metabolites from dying cells in a lymphocyte clonal assay.

A lymphocyte clonal assay developed to quantitate in vivo somatic cell mutations at the hypoxanthine-guanine phosphoribosyltransferase locus was modified in order to study resistance to methotrexate. Even though nucleoside-free culture conditions were used methotrexate was not lethal to lymphocytes plated into micro-wells at greater than 10(2) cells/well. HPLC analysis of supernatants from wells plated initially with 10(4) cells/well in 100 microM methotrexate revealed the presence of micro-molar levels of hypoxanthine and thymidine by the 5th and 8th day of culture respectively. When lymphocytes were plated at less than or equal to 10(2) cells/well in nucleoside free medium, methotrexate was cytotoxic and micro-molar levels of thymidine together with hypoxanthine protected lymphocytes cultured under these conditions from toxicity. Modulation of nucleic acid antimetabolite cytotoxicity by nucleosides and bases has been recognised for some years. Nucleoside free culture conditions have been advocated for studying cellular sensitivity to antifolates to avoid such interfering factors. However our results indicate that metabolites from dying or damaged cells can prevent methotrexate cytotoxicity, further complicating the development of a suitable clonogenic assay for investigating antifolate sensitivity.

Cell Division↗
PubMed1988

Identification of 'non-proliferating' B16 melanoma cells using monoclonal antibody (AD203) against the M1 subunit of ribonucleotide reductase.

Ribonucleotide reductase catalyses a critical reaction in DNA synthesis. Its M1 subunit is present during all proliferative phases of the cell cycle, but apparently not in the quiescent phase G0. We have used a monoclonal antibody (AD203) directed against the M1 subunit to distinguish immunocytochemically proliferating from non-proliferating cultured B16 mouse melanoma cells during exponential growth. The presumption that AD203 unstained cells constituted a non-proliferating fraction was tested by simultaneously counting the cells that failed to incorporate bromodeoxyuridine (BrdU) into DNA during a prolonged BrdU exposure. The proportion of cells which did not incorporate BrdU was found to correlate closely with the proportion not staining with AD203 and therefore presumably lacking the M1 subunit. The respective morphological features of AD203 stained and unstained cells were found not to differ significantly.

Animals↗
PubMed1988

Surveillance for stage I non-seminomatous germ cell tumours of the testis: the optimal protocol has not yet been defined.

Forty-six patients with clinical stage I testicular non-seminomatous germ cell tumours were followed up according to a protocol of active surveillance between 1979 and 1987. The median follow-up time was 40+ months. Thirteen patients (28%) relapsed, predominantly in retroperitoneum and/or lung. Ten of these relapses (76%) occurred within 8 months of orchiectomy. Relapses occurred in 7/35 T1 tumours and 5/10 T2 to T4 tumours. No correlation was detected between the histological type and relapse rate. Three late relapses were diagnosed at 23, 29 and 36 months. Eleven of the relapsed patients remain in prolonged complete remission after PVB chemotherapy +/- surgery; one patient, who initially refused treatment at the time of relapse, has died. Another relapsed with predominant elements of rhabdomyosarcoma intermingled with malignant teratoma in a bone metastasis. He had a partial response to PVB chemotherapy but subsequently died. Thirty-four patients (74%) did not undergo lymphography (LG) and had a higher relapse rate (11/34) than those who had LG (2/12); this was not a statistically significant difference in this small series. The policy of active surveillance is not yet the "state of the art" and should be under constant scrutiny with respect to safety and practice.

Adult↗
PubMed1988

Integrating modalities in cancer management.

The emergence of effective chemotherapy for some tumours, and improved understanding of tumour biology, and of factors limiting disease control by surgery and radiotherapy have led to a multidisciplinary strategy of cancer management for many patients. The clinical and laboratory considerations in this development are summarised, and the results of some treatment programmes which integrate surgery, radiotherapy and chemotherapy are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies.

Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Regional chemotherapy with the use of cisplatin and doxorubicin as primary treatment for advanced sarcomas in shoulder, pelvis, and thigh.

Eight patients who had large sarcomas in the hip, thigh, or shoulder girdle have been described. Three had osteogenic sarcomas, and one each had Ewing's sarcoma, biphasic synovial sarcoma, pleomorphic liposarcoma, undifferentiated spindling sarcoma, and malignant fibrous histiocytoma. All eight tumors showed evidence of regression after intraarterial infusion of cisplatin and Adriamycin (doxorubicin) given over 48 hours at 3-week intervals, for a total of between three and seven courses. Tru-cut needle biopsy specimens of five of the lesions were normal after chemotherapy. However, after resection of the regressed fibrotic tumor in seven of the patients, four contained foci of probably viable malignant cells. These cell foci were intraosseous in three cases and in the wall of a cyst in one case. In the remaining case, tumor in the distribution of the infused artery regressed, but tumor in a region supplied by an artery that was not infused continued to enlarge. In one patient with osteogenic sarcoma in the pelvis, despite a good response to intraarterial chemotherapy that was followed by surgical resection and radiotherapy, tumor recurred in an adjacent area in tissues supplied by an artery not infused. A hindquarter amputation subsequently was required. With the exception of the two cases in which adequate tumor arterial infusion was not achieved, local primary tumor control was accomplished by intraarterial infusion chemotherapy followed by local resection or radiotherapy and local resection in all patients. Four patients are well without evidence of residual or metastatic sarcoma 3.5 years after presentation in the case of an osteogenic sarcoma of shoulder, 2.5 years after presentation in the case of a large pleomorphic liposarcoma of thigh and groin, 20 months after presentation in the case of lower-thigh malignant fibrous histiocytoma, and 1 year after presentation in a child with an osteogenic sarcoma of lower femur.

Adolescent↗
PubMed1987

Proteolipid identified by magnetic resonance spectroscopy in plasma of a patient with borderline ovarian tumour.

Magnetic resonance spectroscopy (MRS) can identify abnormal lipoproteins in the plasma of patients with premalignant and malignant tumours. Proteolipid complexes, 8-11 nm and 25-28 nm in size, were isolated from the plasma of a patient with a borderline ovarian tumour. These complexes, which generated a characteristically long MRS T2 relaxation value (greater than 400 ms), were disrupted by ribonuclease. None of the conventional lipoproteins had a T2 value above 160 ms. Chemical analysis of the proteolipid complexes showed a 20% glycolipid component, and MRS identified a fucosylated molecule as the origin of the long T2 value. 9 months after resection of all tumour, a visible lipoprotein band, possibly lipoprotein (a), persisted in the plasma but neither the long T2 relaxation value nor the 8-11 nm or 25-28 nm particles were present. The long T2 relaxation value in the MRS profile, found in isolated proteolipid and unfractionated plasma and serum of other patients with carcinoma of the ovary and colon, provides a non-invasive method of assaying for cancer.

Adult↗
PubMed1987

Ribosomal RNA gene amplification: a selective advantage in tissue culture.

A CCRF-CEM (human T-cell leukemia) line, initially made resistant to methotrexate by a four-step increase in drug concentration, revealed a large marker of one chromosome #14 in all cells after a 6-month period of culture in the absence of drug. The marker is the result of a triple duplication of both the satellite and stalk. In situ hybridization with 3H-cRNA and NOR banding proved that ribosomal DNA had been amplified and was actively transcribed. Flow cytometric analysis showed a significant increase of RNA versus DNA in G1 cells compared with those of the original drug-resistant parent. The abnormal chromosome appeared after the removal of methotrexate from culture and may be related to the faster doubling time of this line compared with the parent line.

Chromosome Banding↗
PubMed1987

Cytogenetic findings in cell lines derived from four ovarian carcinomas.

Six cell lines, established from four primary ovarian carcinomas were examined cytogenetically. The lines varied greatly in their chromosome complement. All cells from the lines were aneuploid, although one cell line contained two populations having a pseudodiploid and a pseudotetraploid modal chromosome number. Every chromosome group was involved with loss and gain of chromosomes, but some individual chromosomes were more prone to aneuploidy than others. Chromosome #6 was the most stable throughout. Structural changes gave rise to many marker chromosomes. Although most markers were random and the majority unidentifiable, some abnormalities of clonal origin were found. Deletions especially of chromosome #1, were the most common change. Further sequential studies may elicit the origin, stability, and timing of the chromosome abnormalities.

Adenocarcinoma↗
PubMed1987

High quality metaphases from solid ovarian tumors.

Cytogenetic studies of human solid tumor tissue are hampered by poor quality preparations. Using a method of short-term tissue culture developed for ovarian carcinoma specimens, we have obtained large numbers of high quality metaphases suitable for analysis from 19 of 28 ovarian tumors studied.

Chromosome Aberrations↗
PubMed1987

Patient treatment preference in advanced breast cancer: a randomized cross-over study of doxorubicin and mitozantrone.

Twenty-two patients with advanced breast cancer participated in a randomized cross-over study of one cycle each of doxorubicin followed 3 weeks later by mitozantrone or vice versa. Before further treatment, patients selected which drug they wished to continue. Of 18 patients completing the study, 13 chose to continue mitozantrone, 2 doxorubicin and 3 had no preference (P = 0.007). Patients were told to assume similar efficacy of the two drugs and drug preference was based primarily on side-effects. Patient self-assessment of quality of life and physician assigned toxicity scores both indicated that nausea and vomiting, appetite and alopecia were significantly worse following doxorubicin than after mitozantrone. Except for alopecia, no significant period or carry-over effects were noted although the power of the study to detect such interactions was low. This study design may prove useful in enabling patients to select their preference between two treatments of similar efficacy.

Adult↗
PubMed1987

Drug resistance in clinical practice: patterns of treatment failure in patients receiving systemic therapy for advanced breast cancer.

Strategies for overcoming the causes of drug resistance should take account of the patterns of treatment failure seen in clinical practice. We have analysed the patterns of disease progression in 267 patients with advanced breast cancer receiving systemic therapy. First disease progression on therapy most commonly occurred in tissues involved by tumour at the commencement of treatment. However in 40% of patients, first documentation of disease progression included a tissue not previously known to contain metastatic disease. In only 3% of patients was this new tissue the central nervous system. This pattern of disease progression was not influenced by treatment type (i.e. endocrine or cytotoxic), tumour response to treatment, oestrogen receptor status, prior adjuvant cytotoxic treatment, or disease free interval. These results question the wisdom of always ceasing existing therapy and substituting new treatment when progressive disease is first documented.

Antineoplastic Agents↗
PubMed1987

Metastatic adenocarcinoma of unknown primary site. A randomized study of two combination chemotherapy regimens.

Of 101 patients with symptomatic adenocarcinoma or undifferentiated carcinoma of unknown primary site, 95 were evaluable for the effects of two randomized chemotherapy regimens. Forty-eight patients received combination doxorubicin and mitomycin C (DM) and 47 received combination cisplatin, vinblastine and bleomycin (PB). Response rates were not significantly different between the two treatment groups, 42% for DM and 32% for PVB, with an overall response rate of 37.1%. Survival differences for DM and PVB treated groups were not significantly different, with 18 weeks and 25 weeks median survivals respectively. Toxicities were unequal for the two treatment groups with increased haematological toxicity for DM and greater gastrointestinal toxicity for PVB. The authors conclude both therapies were of limited efficacy in the treatment of ACUP patients and emphasize that only symptomatic patients should be considered for such therapies.

Adenocarcinoma↗