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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 271 records · Page 15Linked to original sources
PubMed1993

One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study.

PURPOSE: To determine if prolonged adjuvant treatment (2 years v 1 year) with combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil [5-FU], vincristine, and prednisone [CMFVP]) in poor-prognosis breast cancer patients (estrogen receptor [ER]-negative, stage II to IIIA) would result in improved disease-free and overall survival rates. PATIENTS AND METHODS: Four hundred forty-five women with ER-negative node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) over a period of 5 years (1979 to 1984). Randomized assignments were made to either 1 or 2 years of adjuvant CMFVP. Doses were daily oral cyclophosphamide 60 mg/m2, intravenous (i.v.) weekly methotrexate 15 mg/m2, i.v. weekly 5-FU 400 mg/m2, i.v. weekly vincristine .625 mg/m2 for the first 10 weeks, and prednisone weeks 1 through 6 with doses decreasing from 30 mg/m2 to 10 mg/m2. RESULTS: The median follow-up duration is 8.6 years, with a maximum of 11.3 years. Treatment arms were not significantly different as regards either survival or disease-free survival rates (P = .33 and P = .24, respectively). The five-year survival rate is 57% on the 1-year arm and 62% on the 2-year arm. Patients with three or fewer nodes and premenopausal status were associated with improved survival. Compliance on the 2-year arm was poor, with only 37% completing the full 2 years of treatment. SWOG grade 3 to 4 toxicity was experienced by 47% of patients on the 1-year arm and by 52% on the 2-year arm. There were no treatment-related deaths. CONCLUSION: We conclude that 2-year adjuvant treatment with CMFVP is not an improvement over 1-year treatment. Moreover, 2 years of CMFVP is difficult to complete. However, the results are not definitely negative. A moderate improvement attributed to prolonged chemotherapy, especially among patients with four or more positive nodes, cannot be ruled out.

Adult↗
PubMed1993

The peroxisome proliferator-activated receptor:retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs.

The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of fibrate hypolipidaemic drugs and non-genotoxic rodent hepatocarcinogens that are collectively termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl CoA oxidase, which is elevated about tenfold in the livers of treated rodents. We have previously shown that a peroxisome proliferator response element (PPRE) is located 570 bp upstream of the rat peroxisomal acyl CoA oxidase gene and that PPAR binds to it. We show here that the retinoid X receptor (RXR) is required for PPAR to bind to the PPRE, and that the RXR ligand, 9-cis retinoic acid, enhances PPAR action. Retinoids may therefore modulate the action of peroxisome proliferators and PPAR may interfere with retinoid action, perhaps providing one mechanism to explain the toxicity of peroxisome proliferators. We have also shown that a variety of hypolipidaemic drugs and fatty acids can activate PPAR. This supports the suggestion that the physiological role of PPAR is to regulate fatty acid homeostasis, and provides further evidence that PPAR is the target of the fibrate class of hypolipidaemic drugs. Finally, we have demonstrated that a metabolically stabilized fatty acid is a potent PPAR activator, suggesting that fatty acids, or their acyl CoA derivatives, may be the natural ligands of PPAR.

Animals↗
PubMed1993

Measurement of anaerobic capacities in humans. Definitions, limitations and unsolved problems.

Anaerobic capacity is defined as the maximal amount of adenosine triphosphate resynthesized via anaerobic metabolism (by the whole organism) during a specific mode of short-duration maximal exercise. This review focuses on laboratory measures which attempt to quantify anaerobic capacity; it examines the evidence supporting or challenging the validity of these measures and provides research foci for future investigations. Discussion focuses on anaerobic capacity measured during running and cycling, since almost all data reviewed were collected using these exercise modes. The validity of the oxygen debts (alactic and total), maximal blood lactate and oxygen deficit as measures of anaerobic capacity was examined. The total oxygen debt, now termed the excess post-exercise consumption, was used in investigations in the 1920s and 1930s to quantify anaerobic energy production; it has since been shown to be an invalid measure of anaerobic capacity, since its magnitude is known to be influenced by factors (e.g. temperature, catecholamines, substrate cycling, lactate glycogenesis) other than those directly involved in anaerobic metabolism. Maximal blood lactate, a measure also used in some of those early investigations, is often used in exercise and sports physiology. Opinion on the utility of maximal blood lactate as an estimate of anaerobic (lactic) capacity is, however, divided. Despite problems interpreting the physiological meaning of maximal blood lactate levels (due primarily to acute changes in blood volume), this measure is still used in both research and athletic settings to describe anaerobic capacity. Its use is supported by (a) the high correlations observed between maximal blood lactate and short-duration exercise performance presumably dependent upon anaerobic capacity, and (b) the higher maximal blood lactate values observed in sprint and power athletes (who would demonstrate higher anaerobic capacities) compared with endurance athletes or untrained people. However, training-induced changes in other performance, physiological and biochemical markers of anaerobic capacity have not always been paralleled by changes in maximal blood lactate; its relatively high variability also diminishes its usefulness to athletic populations, since relatively small changes in anaerobic capacity may not be detected by a measure with such high variability. These latter findings may be partially related to the confounding influence of blood volume which often changes in response to short and long term exercise demands. Maximal blood lactate is known to be influenced by the intensity and duration of the preceding exercise bout; therefore, it is plausible that these factors may also influence the degree to which maximal blood lactate accurately reflects anaerobic capacity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1993

Modeling the behavior and attributes of injecting drug users: a new approach to identifying HIV risk practices.

The behaviors and attributes of 503 Scottish injecting drug users were modeled using the linear structural equations program LISREL. Drug use was directly related to prison experience, sexual activity, sharing of injecting equipment, and prostitution. Although the prevalence of HIV among the sample was low (2.0%), the pattern of risk behaviors observed in the data affords potential for future spread of the virus. Harm reduction measures taken by injectors in response to the threat posed by AIDS were inversely related to drug use but, more encouragingly, directly related to awareness of the disease, treatment for drug use, and prostitution.

Awareness↗
PubMed1993

Pitfalls in quality-of-life assessment: lessons from a Southwest Oncology Group breast cancer clinical trial.

There is increasing interest in evaluating the impact of cancer treatment and medical intervention on patient quality of life (QOL). This article reports the findings of a substudy that incorporated the Functional Living Index--Cancer in an ongoing adjuvant breast cancer clinical trial sponsored by the Southwest Oncology Group. The companion study had to be terminated prior to the end of the two-armed, randomized trial because of poor reporting rates over time. Problems with missing data items also occurred. Poor reporting rates in this trial motivated several recommendations for conducting QOL assessment in the cooperative group setting: (a) build support for QOL assessment among the group's leadership, (b) involve physicians and oncology nurses in the study design, (c) identify a QOL liaison at each participating institution, and (d) aggressively monitor the quality and timeliness of data submission.

Activities of Daily Living↗
PubMed1993

The CNS role: evolution within a shared governance environment.

Organizational change has a profound impact on the role of the CNS. Movement in our institution from a centralized structure to a shared governance philosophy redirected the work of the CNS. This article describes the change response spiral that reflects the CNS role evolution and activities required by the CNS to foster the change. Three phases of the response spiral are highlighted: creating a culture, restructuring, and adaptation. CNS activities and experiences associated with the change will be of interest to administrators and CNSs.

Adaptation, Psychological↗
PubMed1992

The ontogeny of peroxisome-proliferator-activated receptor gene expression in the mouse and rat.

The expression of the gene coding for peroxisome-proliferator-activated receptor (PPAR), a novel transacting factor belonging to the steroid superfamily, has been determined in the mouse and rat throughout development using hybridization histochemistry. Messenger RNA is demonstrable in the liver and brown fat from the fetal period onwards and, additionally, in the heart, kidney and gut post-natally. It is proposed that the upregulation of transcription of peroxisomal beta oxidation genes in specific tissues follows binding of the receptor to its natural ligand. Thus PPAR may have an important role in cold adaptation and non-shivering thermogenesis as well as in detoxification.

Adipose Tissue, Brown↗
PubMed1992

The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene.

Peroxisome proliferators are a diverse group of chemicals, including several hypolipidaemic drugs, that activate a nuclear hormone receptor termed the peroxisome proliferator activated receptor (PPAR). The peroxisomal enzyme acyl CoA oxidase (ACO) is the most widely used marker of peroxisome proliferator action. We have examined the 5' flanking region of the rat ACO gene for sequences that mediate the transcriptional effect of peroxisome proliferators and have identified an element located 570 bp upstream of the ACO gene that confers responsiveness to the hypolipidaemic peroxisome proliferator Wy-14,643. This peroxisome proliferator response element (PPRE) contains a direct repeat of the sequence motifs TGACCT and TGTCCT and binds PPAR. These data therefore indicate an important role of PPAR in mediating the action of peroxisome proliferators including the induction of ACO.

Acyl-CoA Oxidase↗
PubMed1992

Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria.

The Southwest Oncology Group, in cooperation with the National Cancer Institute and the other major cooperative oncology groups, has participated in the development of new toxicity criteria for reporting the results of cancer clinical trials. The new criteria (NCI Common Toxicity Criteria) respond to a recognized need to: (1) report toxicities consistently among cooperative groups, particularly for shared 'intergroup' clinical trials; (2) strive for comparability in toxicity reporting among clinical trials; and (3) recognize new toxicities accompanying new classes of anticancer treatment modalities. The Southwest Oncology Group has extended the toxicity criteria, incorporating additional new criteria for biological agents, radiation therapy, surgery, and hormonal agents. In addition, endpoint definitions and response criteria are discussed. These have been developed in response to previous uncertainties in clinical trials objectives, to limitations in the resolution of imaging methods, and to demands for greater rigor in response and endpoint definitions. Toxicity criteria, endpoint definitions, and response criteria are tabulated.

Combined Modality Therapy↗
PubMed1992

Proportional hazards and recursive partitioning and amalgamation analyses of the Southwest Oncology Group node-positive adjuvant CMFVP breast cancer data base: a pilot study.

Several putative prognostic factors have been identified in node-positive breast cancer patients, but their importance needs to be clarified in a uniformly treated population. The objectives of this investigation were: 1) to describe the characteristics of a uniformly treated node-positive data base; 2) to use proportional hazards (Cox) and recursive partitioning and amalgamation (RPA) multivariate models to assess the importance of potential prognostic factors for disease-free and for overall survival; and 3) to define prognostic groups with different disease-free survival and survival outcomes with RPA. A data base of 768 node-positive patients enrolled on 1-year adjuvant CMFVP arms of four SWOG trials was formed. Variables were number of positive nodes, age, age at menopause, menopausal status, ER status, ER and PgR levels (for RPA only), tumor size, race, breast cancer in mother, and obesity index. Independent predictors of both disease-free and overall survival in the Cox models were: number of positive nodes (4-6 worse than 1-3, and better than greater than 6); the age/menopause category (age greater than or equal to 35/premenopausal better than age less than 35/premenopausal and better than postmenopausal); and ER status (patients on ER-negative study worse than others). The RPA for disease-free survival defined four subgroups based on nodes, menopausal status, tumor size, and age at menopause (5-year recurrence-free rates = 73%, 52%, 38%, and 15%). The RPA for survival found four prognostic groups, defined only by the number of positive nodes and ER and PgR levels (5-year survivals = 91%, 72%, 56%, and 37%). Both RPAs suggested interesting refinements of the results of the Cox models. In the RPA for disease-free survival, best node cutoffs differed by menopausal status, tumor size was important only in postmenopausal patients with few positive nodes, and age at menopause emerged as an independent predictor of recurrence potential. And, the RPA for survival showed that node cutoffs differed according to ER level. Thus, these analyses underscore the value of simple, clinically available prognostic factors and suggest the possible need to reconsider the definition of good and poor risk patient groups in future adjuvant trial design.

Adult↗
PubMed1992

Nuclear receptors and chemical carcinogenesis.

A number of non-genotoxic chemical carcinogens can recognize specific intracellular proteins. These cellular targets include members of the nuclear receptor family of ligand-activated transcription factors. Some non-genotoxic carcinogens appear to mimic the action of hormones and growth factors and perturb signal transduction pathways. Their carcinogenic activity may therefore result from the persistent stimulation of such pathways, promoting the growth of initiated cells.

Animals↗