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Biomedical subjects

C J Williams

Publications and source records attributed to C J Williams.

At least 109 records · Page 6Linked to original sources
PubMed1992

Meta-analysis of the role of platinum compounds in advanced ovarian carcinoma. The Advanced Ovarian Cancer Trialists Group.

This paper presents a systematic overview or meta-analysis of 54 randomized clinical trials testing a variety of chemotherapeutic approaches in advanced ovarian carcinoma. Prolonged follow-up data are available for most patients and individual patient data were made available for all patients; analysis was made on the basis of "intention to treat." Our report concentrates on two comparisons: (1) platinum alone versus platinum in combination, which appears to show a long-term survival advantage for the combination (however, the platinum dose in the single-agent arm was relatively low); and (2) carboplatin versus cisplatin, which shows no obvious survival differences. It is striking that no single study to date has been large enough to detect the modest survival differences expected from current therapy. Consequently, a series of international studies have been initiated. The International Collaborative Ovarian Neoplasm (ICON) group will examine the role of adjuvant chemotherapy in early ovarian cancer (ICON 1) and will compare carboplatin with cisplatin, doxorubicin, and cyclophosphamide in more advanced disease (ICON 2).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cancer.

Explore the source record for details and available documents.

Adult↗
PubMed1991

Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates.

We estimated genetic effects on bone density in pre- and postmenopausal twins and critically considered the assumptions of the twin model. Bone mass in the radius, lumbar spine, and hip, anthropometric measurements, usual calcium and caffeine intake, tobacco and alcohol use, number of pregnancies and live births, menstrual history, usual physical activity, and medical history were measured in a volunteer sample of 171 twin pairs [124 monozygotic (MZ) and 47 dizygotic (DZ)], aged 25-80, free of diseases known to affect bone mass or mineral metabolism. At all skeletal sites, MZ intraclass correlations exceeded DZ correlations for both pre- and postmenopausal women, yielding highly significant estimates of heritability for bone mass. Adjustments for height, age, and environmental characteristics did not reduce the heritability estimates. However, many of these estimates were unrealistically high, suggesting some violation(s) of the assumptions of the twin model. Thus, the familial resemblance in bone mass is due primarily to genetic effects at all skeletal sites and at all ages, although the importance of genetic effects is diminished with aging, as evidenced by increasing within-MZ pair variability in older women. Because of failures in the assumptions of the twin model, however, particularly the greater MZ environmental similarity and the probability of gene interaction, heritability estimates are probably too high and require cautious interpretation.

Adult↗
PubMed1991

Stress-enhanced ion release--the effect of static loading.

Static stresses affect the corrosion behaviour of 316L stainless steel, Ti-6AI-4V, and a Co-Cr-Mo alloy. Several corrosion parameters are modified by stress, although the changes most relevant to the clinical situation are lowering of breakdown potentials and increases in corrosion currents. AC impedance techniques to measure capacitance allowed the latter effect to be partitioned into components of true current density and true area changes. Although loading past the yield point can definitely cause stress-enhanced ion release (SEIR), it is not required. SEIR can also be caused by elastic loading. The basic mechanism for this phenomenon appears to be passive film disruption followed by slow repassivation kinetics. Polished, grit-blasted, and porous-coated surfaces were examined. The porous-coated materials seemed to be most susceptible to SEIR. If effects similar to those observed here apply to in vivo conditions, then tests on unstressed alloys in vitro could grossly underestimate ion release rates of stressed implant devices in vivo.

Alloys↗
PubMed1991

Recognition of peptidyl epitopes by polymorphic epithelial mucin (PEM)-specific monoclonal antibodies.

Peptidyl epitope recognition by several murine monoclonal antibodies (MAbs E29, H23, HMFG-1, HMFG-2, MA5, MA6 and MA9) which react with the polymorphic epithelial mucins [PEM; epithelial membrane antigen (EMA)] was studied by using ten synthetic peptides representative of the 20 residue tandem repeat as test antigens. Antibody binding to 6-10 residue overlaps and to peptides having a common carboxy-terminus and staggered amino-termini (8-31 residues) was assessed by solid phase and competition ELISA techniques. From these analyses, all MAbs except MA9 were found to react predominantly with the carboxy-terminal half of the repeat motif. Polyclonal antibody responses in mice immunized with intact EMA/PEM-containing preparations also displayed significant reactivities against synthetic repeat peptide antigens and, conversely, synthetic peptides as carrier-conjugated immunogens induced antibodies recognizing intact antigens. These results are discussed vis-à-vis peptide conformation, the potential effects of O-glycosylation on secondary structure, and the possible effects of these parameters on immunogenicity and antigenicity.

Amino Acid Sequence↗
PubMed1990

Multiple protein forms of the human breast tumor-associated epithelial membrane antigen (EMA) are generated by alternative splicing and induced by hormonal stimulation.

Cloning and sequencing of epithelial membrane antigen (EMA) has demonstrated the existence of a variable number of tandem repeats (VNTR) flanked by unique sequences, and alternative splicing has been proposed to result in secreted and membrane-bound antigenic forms. Antisense oligonucleotides, specific for the VNTR region and various alternative splice forms, were used as probes to define EMA transcripts in poly A+ RNA from a mucinous breast tumor cell line. The BT549 line has been shown to exhibit enhanced expression and secretion of EMA when the cells are cultivated in a medium supplemented with hydrocortisone and insulin, and Northern blot analysis demonstrated that EMA-related RNA transcripts are commensurately enhanced. As a result of the large increase in EMA RNA levels, two major transcripts in BT549 have been identified as coding for either the secreted or transmembrane EMA forms and two antigenic forms have been immunoprecipitated from BT549 cell layer and medium translation products.

Antigens, Neoplasm↗
PubMed1990

Breast tumor radioimmunodetection with a 111In-labeled monoclonal antibody (MA5) against a mucin-like antigen.

Monoclonal antibody MA5 recognizes a determinant displayed on high molecular weight antigens associated with secretory and malignant breast epithelial cells. MA5 reactivity with greater than 95% of primary and metastatic breast tumors, surface expression of the antigen, as well as its ability to localize within breast tumor xenografts prompted this initial study to determine the efficacy of MA5 to localize breast tumors by radioimmunoscanning. A total of 17 patients was monitored, each receiving 2 mg of purified MA5 labeled with 5 mCi of 111In. Some patients also received 3 or 18 mg of unlabeled carrier antibody (MA5); no serious allergic reactions were noted. Primary tumors, bone lesions, soft tissue recurrences, and lung metastases greater than 3 cm in diameter were detectable, whereas only one lesion (hilar node) less than 3 cm was localized. Significant antibody accumulation was noted in the liver and less significant uptake in the spleen and bone. The extensive fibrosis and poor vascularization of breast tumors may partly explain the limited sensitivity obtained thus far. The imaging results obtained with MA5 are compared with other antibodies which we show recognize the same antigens.

Antibodies, Monoclonal↗
PubMed1990

A phase II study of oral idarubicin in advanced recurrent or refractory ovarian carcinoma.

Oral idarubicin (40 mg/m2 in 3-4 divided doses over 24 h every 21 days) was tested in a group of patients with drug-resistant ovarian carcinoma. None of 13 patients responded and the study was discontinued. Toxicity was acceptable, with neutropaenia being dose-limiting. It seems unlikely that idarubicin has significant activity in this disease although phase II studies should ideally be conducted in less heavily pretreated patients.

Administration, Oral↗
PubMed1990

A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix.

A total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic deaths. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.

Adult↗
PubMed1990

Social contact and sibling similarity: facts, issues, and red herrings.

We consider evidence that shared experience is associated with sibling resemblance and report new analyses of our earlier data to assess the magnitude and meaning of that association. We cite recent Swedish studies of early separated twins and present new data from reared-apart twins in Finland. Results of these analyses confirm our earlier conclusion that, for some dimensions of personality and life-style, twins who cohabit longer into adulthood and twins who retain closer contact after separation are more alike. Further, new analyses here reported are consistent with our earlier inference that, for neuroticism and consumption of alcohol, cotwin differences in contact precede, and causally contribute to, differences in behavioral similarity.

Female↗
PubMed1990

Bone mass and anthropometric measurements in adult females.

Bone mass and anthropometrics were measured in 342 adult female twins, aged 25-79 (mean = 44.1 years) for the purpose of: (1) identifying which anthropometric measurements were most strongly associated with bone mass at various skeletal sites, and (2) determining the accuracy of combinations of these measurements in the prediction of bone mass. Among the eight skinfolds measured, the subscapular site was more strongly correlated with all bone mass measurements than any other skinfold. Similarly, calf circumference (among four sites) and biacromial width (among five frame size measurements) provided the strongest correlations within these groups of anthropometrics with all bone sites. The somewhat surprising consistency of these results was then tested in multivariable models for the prediction of bone mass. For the entire study group, each of the anthropometric measurements (subscapular skinfold, calf circumference and biacromial width) were independent, significant predictors of bone mass, even when height, weight and age were included in the models. These data suggest that frame size, muscularity and adiposity have independent effects on the skeleton, and that single measurements of each of these anthropometric characteristics are associated with all skeletal sites.

Adipose Tissue↗
PubMed1990

A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer.

The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contentious. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIIb or IV NSCLC were randomly assigned to cisplatin 120 mg m-2 on days 1 and 29 and vindesine 3 mg m-2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Responders continued chemotherapy at the same doses though cisplatin being given 6 weekly x 4 and the vindesine 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (median 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dissemination (IIIb), median survival was 45 weeks in the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinuing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treatment. Further phase III studies of chemotherapy in advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study.

Retrospective studies have recently demonstrated a significant correlation between dose intensity of chemotherapy and response rates and survival in various diseases including epithelial ovarian carcinoma. As part of a proposed randomised trial to assess the effect of dose intensity on outcome in ovarian carcinoma, a pilot study has been undertaken to determine the toxicity and efficacy of the high intensity therapy. Nineteen patients with advanced ovarian carcinoma received initial treatment with cisplatin 120 mg m-2 i.v. day 1, and cyclophosphamide 1,000 mg-2 i.v. day 1, given at 21-day intervals for six cycles. The average relative dose intensity of this therapy is 1.14 when compared with the CHAP regimen. Severe toxicity was experienced by most patients. The median received average relative dose intensity was 0.90, with only one patient receiving treatment to the proposed intensity. Randomised studies of the effect of dose intensity in ovarian carcinoma are essential, but an initial step must be to assess whether the proposed high dose treatment can be delivered.

Adult↗
PubMed1990

Enhanced expression and secretion of an epithelial membrane antigen (MA5) in a human mucinous breast tumor line (BT549).

The mouse monoclonal antibody MA5, generated versus a membrane-enriched extract of breast cancer metastatic to liver, detects one or two high molecular weight species (greater than 200 kD) in breast tumor membranes, human milk fat globule membranes, and various breast tumor cell lines. From comparative studies of five breast carcinoma lines (BT20, BT549, MCF-7, T47D, and ZR75-1), as well as an epithelial line established from milk (HBL-100), we report the stimulation of expression of MA5-reactive antigen in a mucinous breast tumor cell line (BT549) through the use of a culture medium supplemented with charcoal-absorbed fetal calf serum, insulin, and hydrocortisone. Large amounts of aggregated MA5-reactive antigen are secreted into the culture medium and can be recovered from the media for further purification by centrifugation. These findings suggest that BT549 cells, grown in the special nutritive medium, may be useful in providing an ample source of epithelial membrane antigen (also termed polymorphic epithelial mucin) for standardization of clinical assay protocols, as well as provide a model system for studies of the regulation of expression for this class of antigens in breast carcinoma.

Adenocarcinoma, Mucinous↗