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J Waxman

Publications and source records attributed to J Waxman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Epithelial mucin expression in bladder cancer: correlation with pathological and clinical parameters.

Recently, attention has been drawn to the role of polymorphic epithelial mucin (PEM) as a possible target for cancer immunotherapy. To investigate the expression of this molecule in bladder tissue, we used two mouse monoclonal antibodies (HMFGI and HMFG2) raised against the core protein of the PEM. The localization of these two anti-PEM antibodies was examined in normal (n = 10), inflammatory (n = 10) and malignant (n = 67) bladder tissue samples with the use of a three-step avidin-biotin method. For HMFG1 and HMFG2 localization was successful in 78% and 60% of the bladder cancer samples, respectively, where as they were localized only in 30% and 40% of normal bladder tissue samples, respectively. Staining of either antibodies did not correlate with the grade, stage, or survival of bladder cancer patients. We conclude that PEM is frequently overexpressed by bladder cancer cells and HMFG1 is the antibody of choice to be used as a carrier of a cytotoxic agent for application of intravesical targeted therapy of bladder cancer.

Aged↗
PubMed2000

Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure.

The higher incidence of coronary artery disease in men is often attributed to androgens. Arterial compliance or 'stiffness' is increasingly regarded as a modifiable risk factor for cardiovascular disease. We wanted to look at the effects of complete androgen withdrawal, on arterial compliance in men. We performed arterial compliance studies on 12 men with complete androgen deprivation as treatment for prostate cancer, and on 12 age-matched healthy controls. Central pulse wave velocities were significantly higher in the androgen-deprived men (14.2 +/- 2.7 vs 11.8 +/- 1.6 m/sec, P = 0. 02). The cases tended to have higher brachial systolic pressures than controls though this difference was not significant (P = 0.2). We conclude that androgen withdrawal is associated with a reduction in central arterial compliance. Conversely androgen withdrawal does not affect peripheral arterial compliance. It is unlikely that the presence of normal concentrations of androgens can explain the sex difference in mortality rates. Longitudinal studies are needed for further evaluation. Journal of Human Hypertension (2000) 14, 395-397

Aged↗
PubMed2000

Adjuvant mitozantrone chemotherapy in advanced prostate cancer.

OBJECTIVE: To assess the role of mitozantrone, active in relapsed prostate cancer, as an adjuvant to hormonal treatment in patients with advanced prostate cancer. PATIENTS AND METHODS: Between October 1990 and May 1995, 96 patients were entered into a stratified, randomized, single-institution study of hormonal therapy with a luteinizing hormone-releasing hormone agonist and flutamide, with or without four cycles of adjuvant mitozantrone. Of these, 93 patients were evaluable and the results were analysed in June 1999. RESULTS: Patients with localized prostate cancer receiving adjuvant chemotherapy had a higher initial objective response rate (95% vs 53%, P = 0.008) and median survival (80 vs 36 months, P = 0.04) than patients who were treated with hormonal therapy alone. There was no advantage to adjuvant chemotherapy in patients with metastatic prostate cancer. There were insignificant advantages to chemotherapy in overall response rates (55% vs 39%, P = 0.3) and PSA responses (82% vs 64%, P = 0.11). There was no difference between the patient groups in time to treatment failure. CONCLUSION: There was a survival advantage in using adjuvant mitozantrone in patients with locally advanced prostate cancer. Although the study comprised relative few patients, the follow-up period was long and the advantage significant. We recommend that the study be extended to include more patients.

Aged↗
PubMed1999

High prevalence of the thermolabile methylenetetrahydrofolate reductase variant in Mexico: a country with a very high prevalence of neural tube defects.

Neural tube defects (NTD) are highly prevalent in the Mexican population. According to data from the Registry and Epidemiological Surveillance of External Congenital Malformations (RYVEMCE), at least 1 in 250 conceptions that reach 20 weeks of pregnancy or more has a NTD. This number is three to four times higher than that observed in other related ethnic groups. A common novel mutation (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene is considered an associated risk factor for NTD and other malformations. Studies in different populations agree that the prevalence of the homozygote for the mutated allele is higher in cases of NTD than in controls. In a meta-analysis recently published, the mean prevalence of the homozygote for the mutation was 9.2% for different groups of European controls and 16.4% in NTD cases from the same populations. This prompted us to investigate the frequency of the normal (C) and the mutant (T) alleles and the prevalence of the expected (CC, CT and TT) genotypes in 250 healthy Mexican women from different parts of the country. The proportion of CC (17.6%), CT (47.6%), and TT (34. 8%) genotypes found, and the gene frequencies of 0.414 and 0.586% for the C and T alleles, respectively, confirmed the very high prevalence of the mutant allele and the TT genotype in the sample studied. Comparisons with studies done in Holland, Ireland, the United States, Japan, and other ethnic groups showed highly significant differences, with an average OR of 5.8 (95% Cl 3.4-10.3) for a Mexican being homozygous for the mutation. These findings may explain an important part of the high prevalence of NTD observed in our population.

Alleles↗
PubMed1999

Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations.

Differential gene expression between the androgen sensitive human prostate cancer cell line LNCaP and an insensitive clonal variant, LNCaP-r, was demonstrated by suppression subtractive hybridization. Twenty-one sequences were identified of which 9 are homologous to known genes, 11 are represented by expressed sequence tags (ESTs), and 1 is novel. We present data for 5 of 7 sequences confirmed to be differentially expressed by Northern blot analysis and semiquantitative RT-PCR. Only one gene, fibronectin (FN), was highly overexpressed (>60-fold) in LNCaP-r cells, consistent with previously reported overexpression of FN in prostate cancer. Four sequences were down-regulated in LNCaP-r cells, including an inactive variant of the E2 ubiquitin conjugating enzyme (UEV-1), a novel metalloproteinase-related collagenase (PM5), and a potential tumor suppressor gene (breast basic conserved gene, BBC1). UEV-1 is multifunctional, regulates the cell cycle via cdk1, has homology to MMS2 and likewise functions as a DNA protection protein, and also has homology to TSG101. Aberrant splice variants of TSG101 occur frequently in both breast and prostate cancer, but its mechanism of action is unknown. FN, BBC1, and UEV-1 localize to regions of chromosomal aberration (2q3.4, 16q24.3, and 20q13.2, respectively) associated with advanced prostate cancer and thus may be highly relevant to disease progression.

Androgen Antagonists↗
PubMed1999

Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy.

AIM: To investigate the correlation between androgen receptor expression and fibroblast growth factor 8 (FGF8) mRNA levels. METHODS: 39 human prostate cancers and 14 benign prostatic hypertrophy specimens were examined immunohistochemically for androgen receptor expression and by in situ hybridisation and reverse transcription polymerase chain reaction for FGF8 expression. RESULTS: In 39 tumours there was a statistically significant negative correlation between tumour grade and FGF8 expression and a positive correlation between FGF8 and androgen receptor expression. All 14 benign hypertrophy specimens expressed moderate to high levels of FGF8 and androgen receptor. CONCLUSIONS: Loss of FGF8 may be a factor involved in the development of prostatic cancer.

Fibroblast Growth Factor 8↗
PubMed1998

British urological surgery practice: 2. Renal, bladder and testis cancer.

OBJECTIVE: To investigate the management of urological malignancies in the United Kingdom. METHODS: A postal survey of consultant urologists and general surgeons with an interest in urology was conducted to examine current clinical practice in urological malignancies. RESULTS: Completed questionnaires were received from 273 consultant surgeons who saw an estimated total of 13241 new patients with renal, bladder or testis cancer per year; 82% had access to on-site oncology services and in general there was a consensus in the answers given. Most respondents advised active treatment of an asymptomatic primary renal cancer in the presence of metastases and a significant proportion of patients with metastases were not prescribed immunotherapy nor were offered a multidisciplinary approach for their condition. Forty-six per cent of patients with testis cancer received no advice to store sperm before chemotherapy and there were varied opinions as to the need for surgical resection of residual masses after completion of chemotherapy. CONCLUSION: This survey showed minor variations in the management of renal, bladder and testis tumours in the UK. Consensus management guidelines for urological malignancies and a change in the working relationships between urologists and oncologists is required, to improve the outcome of patients with urological malignancy.

Carcinoma, Renal Cell↗
PubMed1998

Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer.

PURPOSE: We studied the expression of alpha-, beta-, gamma- catenin and E-cadherin in transitional cell carcinoma (TCC) and normal bladder epithelium and correlated these results with pathological and clinical parameters. MATERIALS AND METHODS: We used an avidin-biotin immunoperoxidase technique to examine the cellular localization of alpha-catenin, beta-catenin, gamma-catenin and E-cadherin in 68 TCC and 14 normal bladder biopsies. RESULTS: E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were expressed in a normal membranous pattern in all normal bladder epithelium specimens. Loss of normal surface E-cadherin, alpha-catenin, beta-catenin and gamma-catenin expression was found in 52/68 (76.4%) tumors, 57/68 (83.8%) tumors, 54/68 (79.4%) tumors and 54/68 (79.4%) tumors (p <0.001). There was a significant correlation between the loss of normal membranous expression of catenins and E-cadherin and increased grade (p <0.05). A highly significant correlation was observed between the loss of expression of E-cadherin, alpha-catenin and gamma-catenin, but not beta-catenin, with increased TNM stage (p <0.05). The abnormal expression of gamma-catenin as well as E-cadherin was correlated with poor survival (p <0.05). CONCLUSIONS: E-cadherin-gamma-catenin complex may be a useful prognostic marker in bladder cancer. Work is in progress to establish whether normal membranous catenin expression can be enhanced by gene transfer or biological therapy to induce a less invasive and metastatic phenotype.

Aged↗
PubMed1997

Gene therapy for prostate cancer.

Over the last decade gene therapy has emerged as probably the sexiest research topic in biology. Whilst few people would attach the same adjective to clinical studies on prostate cancer, the rise in mortality from this very common tumour coupled to the deficiencies of current therapies have kindled research on this malignancy. This article covers the overlap between these disciplines and describes laboratory and clinical experiments that investigate genetic manipulation for the management of prostate cancer.

Antisense Elements (Genetics)↗
PubMed1997

Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter.

Fourteen patients with previously treated, locally advanced/metastatic transitional cell carcinoma (TCC) of the bladder or ureter received paclitaxel at a dose of 200 mg m-2 administered as a 3-h infusion every 21 days. The activity of paclitaxel in this group of patients was modest. The response rates were one partial response (PR) (7%) and three stable disease (SD). There were two early deaths.

Adult↗
PubMed1997

British urological surgery practice: 1. Prostate cancer.

OBJECTIVE: To investigate the treatment of prostate cancer in the United Kingdom. METHODS: A postal survey was conducted of consultant urologists and general surgeons with an interest in urology to assess the current patterns of management of patients with prostate cancer in the UK and to determine patterns of clinical practice. RESULTS: Two-hundred and seventy-four replies were analysed. Radical radiotherapy (50%) and radical prostatectomy (29%) were the most favoured treatment options for patients < 70 years old with poorly differentiated T1 disease; for those aged > 70 years, active treatment was favoured by 183 (67%) consultants with radical radiotherapy (37%) and hormonal intervention (29%) the most frequent choices. In well-differentiated T1 disease, active treatment was favoured by 226 (83%) of consultants for patients < 70 years, with radical prostatectomy (44%) the most frequent choice. For patients > 70 years, observational management was preferred by 190 (69%) of consultants. In poorly differentiated T1 prostate cancer, active treatment was favoured by 252 (91%) for patients < 70, with radiotherapy (50%) the most frequent choice and for patients > 70 years, active treatment was favoured by 67% with radical radiotherapy the most common preference being chosen, by 102 (37%). For asymptomatic locally advanced disease, 55% of consultants favoured active treatment, whilst 63% favoured the active treatment of asymptomatic metastatic disease. For patients with symptomatic metastatic disease, GnRH agonist therapy was the treatment of choice of 66% of urologists and was given as monotherapy by 44% or as part of maximal androgen blockade by 22%. In clinical practice, 82% of urologists have close links with oncology, available through joint clinics or on-site referral. However, < 5% of urologists refer patients to an oncologist before the development of hormone refractory disease. At relapse, only 53% of urologists referred their patients to oncologists or palliative-care clinicians. A wide variety of hormonal treatments was offered at relapse; only 24% of urologists treated their patients by antiandrogen withdrawal or introduction, which is currently the most effective second-line hormonal treatment for recurrent prostate cancer. CONCLUSION: There is a wide variation in the clinical management of prostate cancer and we recommend the establishment of standards of practice.

Attitude of Health Personnel↗