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Biomedical subjects

Y Fradet

Publications and source records attributed to Y Fradet.

At least 37 records · Page 2Linked to original sources
PubMed1999

Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors.

The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 index in superficial papillary bladder tumors and to correlate it with the S-phase fraction (SPF) measured by flow cytometry. Three hundred nineteen patients with newly diagnosed superficial (pTa, pT1) bladder tumors were included between September 1990 and April 1992. Patients with bladder carcinoma in situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, whereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-67 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The relation between Ki-67 expression and prognostic variables (stage, grade, tumor size, multifocality, age, and sex) was investigated by the chi-square test. Cox regression was used to describe the association between Ki-67 and tumor recurrence in 308 patients with follow-up while adjusting for potentially confounding prognostic variables. The frequency of high Ki-67 expression (> or =10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patients experienced tumor recurrence in a median follow-up of 68 months. Stage, grade, tumor size, and multifocality were all independent predictors of recurrence. Ki-67 index greater than 10% was found to be an independent predictor of tumor recurrence among patients with tumors larger than 3 cm in diameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation was observed between Ki-67 expression and the SPF (Spearman's correlation coefficient = 0.23, P = .004). In addition, aneuploid tumors had significantly higher expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Moreover, patients with DNA aneuploid bladder tumors were more likely to have more than 10% Ki-67-positive cells than those with diploid tumors. In patients with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those with tumors larger than 3 cm.

Aged↗
PubMed1999

CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group.

OBJECTIVES: To test the hypothesis that neoadjuvant androgen ablation before radical prostatectomy reduces the likelihood of biochemical progression at 36 months. METHODS: Two hundred thirteen patients with localized prostate cancer were randomized to radical prostatectomy alone (Sx, n = 101) or a 12-week course of 300 mg of cyproterone acetate daily followed by surgery (CPA, n = 112). Biochemical progression (two consecutive detectable prostate-specific antigen [PSA] values) was determined for the entire group and by baseline PSA, Gleason score, clinical stage, and pathologic stage. RESULTS: The probability of biochemical progression at 36 months was similar in both groups (CPA 40.2%, Sx 30.1%; P = 0.3233). CPA patients with baseline serum PSA between 25 and 50 ng/mL had a lower probability of biochemical progression (CPA 63.5%, Sx 84.6%; P = 0.0038). No difference in the probability of biochemical progression was seen between groups when analyzed by clinical stage or Gleason score. When analyzed by pathologic margin status, no difference was observed in the probability of biochemical progression in patients with organ-confined disease (P = 0.4484). There was a trend for a higher probability of progression in the neoadjuvant arm in patients with positive and negative surgical margins (P = 0.0105, P = 0.0459; alpha = 0.005 with Bonferroni adjustment). CONCLUSIONS: Neoadjuvant androgen ablation with CPA reduces the positive margin rate significantly but does not result in a difference in biochemical progression at 3 years. This may be due to a lack of sufficient follow-up, insufficient power of the trial to demonstrate a small benefit, or a true lack of benefit of neoadjuvant androgen ablation before radical prostatectomy.

Androgen Antagonists↗
PubMed1999

Dietary fat and prostate cancer survival.

OBJECTIVES: Relationships between dietary factors and the incidence of prostate cancer have emerged from epidemiologic and laboratory studies, but there are no published data on the relationship between diet and disease progression among prostate cancer patients. We studied the association between dietary fat intake and prostate cancer survival. METHODS: We prospectively followed 384 men diagnosed with prostate cancer between 1990 and 1992 in the Quebec City area. On average 3 months following diagnosis, trained nutritionists interviewed the men on their usual diet using a diet history questionnaire. Deaths during follow-up were documented through record linkage with the provincial mortality file and review of hospital records. Cox proportional hazard models were used to estimate the relative risk of dying from prostate cancer associated with terciles of fat intake, expressed as percent of dietary energy, while controlling for prognostic factors and total energy. RESULTS: The median duration of follow-up was 5.2 years. During the follow-up period 32 patients died of prostate cancer and 39 died of other causes. After controlling for grade, clinical stage, initial treatment, age and total energy intake, we found that saturated fat consumption was significantly associated with disease-specific survival (two-sided p-value = 0.008). Compared to men in the lower tercile of saturated fat, those in the upper tercile had three times the risk of dying from prostate cancer (relative risk = 3.1, 95% confidence interval: 1.3-7.7). CONCLUSIONS: Our findings suggest that saturated fat is related to disease-specific survival and that, if this relation is causal, a moderate reduction of its intake might reduce the risk of dying from prostate cancer.

Aged↗
PubMed1999

Dietary fat and prostate cancer progression and survival.

BACKGROUND: The association between dietary factors and the occurrence of prostate cancer has been studied extensively, but there is, as yet, no published study on the relationship between diet and disease progression among prostate cancer patients. We studied the association between dietary fat intake and prostate cancer survival. METHODS: We prospectively followed 384 men diagnosed with prostate cancer between 1990 and 1992 in the Quebec City area who participated in a case-control study of diet in relation to prostate cancer occurrence. Trained nutritionists interviewed the men on their usual diet using a diet history questionnaire. Deaths in the follow-up were documented through record linkage with the provincial mortality file and review of hospital records. The cause of death was taken as written on the death certificate. Cox proportional hazards models were used to estimate the relative risk of dying from prostate cancer associated with terciles of fat intake, expressed as percent of dietary energy, while controlling for prognostic factors and total energy. RESULTS: The median duration of follow-up was 5.2 years. During the follow-up period, 32 patients died of prostate cancer and 39 died of other causes. The 5-year disease-specific survival was 91%. After controlling for grade, clinical stage, initial treatment, age and total energy intake, we found that saturated fat consumption was significantly associated with disease-specific survival (p = 0.008). Compared to men in the lower tercile of saturated fat, those in the upper tercile had three times the risk of dying from prostate cancer (hazards ratio 3.13, 95% confidence interval 1.28-7.67). CONCLUSION: Our findings suggest that, if saturated fat is causally related to disease-specific survival, a moderate reduction of its intake below 10% of energy should reduce the risk of dying from prostate cancer. This dietary goal is already recommended for health promotion and primary prevention of heart disease and cancer.

Aged↗
PubMed1999

Downward trend in prostate cancer mortality in Quebec and Canada.

PURPOSE: If new treatment strategies and screening for prostate cancer are effective they should reduce prostate cancer mortality. In this review we monitored prostate cancer mortality rates in Quebec and in Canada. MATERIALS AND METHODS: We obtained data on all deaths from prostate cancer between 1976 and 1997 in Quebec, and 1976 and 1996 in Canada. We calculated age standardized mortality rates and assessed changes with time. RESULTS: Prostate cancer mortality rates increased regularly until 1991 in Quebec and Canada. After 1991 the rates decreased moderately until 1995 and then more markedly in 1996. There was a further decline in 1997 in Quebec. Overall, age standardized prostate cancer mortality rates declined by 23% in Quebec between 1991 and 1997, and by 9.6% in Canada between 1991 and 1996. The mortality decline was observed for all age groups but was more pronounced among men younger than 75 years. CONCLUSIONS: Until 1995 the trends in prostate cancer mortality in Quebec and Canada were similar to those observed in the United States. Our data suggest that a sharper decline has occurred since 1995. It is of primary importance to identify the causes of the mortality decline. As prostate cancer mortality rates declined relatively early after the initiation of widespread screening with prostate specific antigen, it is unlikely that screening has as yet contributed in a major way to the decline. It is more likely that the mortality reduction is a consequence of better prostate cancer management or improved treatment modalities.

Age Distribution↗
PubMed1999

Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence.

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.

Aged↗
PubMed1999

Electromotive drug administration of lidocaine as an alternative anesthesia for transurethral surgery.

PURPOSE: A multicenter study was undertaken to evaluate the safety, efficacy and cost of electromotive drug administration of intravesical lidocaine to produce bladder local anesthesia as an alternative to traditional methods of spinal or general anesthesia. MATERIALS AND METHODS: A total of 94 patients were enrolled in the study who had either a history of bladder tumor that required cold cup bladder biopsy with fulguration for possible recurrence as a comparison trial, a bladder tumor treated with transurethral resection/fulguration or benign prostatic hyperplasia/carcinoma treated with transurethral resection. Pain scores using a Verbal Rating Scale were recorded for each individual biopsy, fulguration and resection event. Data for direct and indirect costs were collected using a standardized form for each patient to capture the details of the procedure, including times, drugs and disposables for each patient. RESULTS: There was a significant reduction in pain for patients who received electromotive intravesical lidocaine compared to no anesthesia for biopsy (p<0.03). Similarly, electromotive intravesical lidocaine for bladder biopsy and transurethral bladder tumor resection/fulguration was associated with higher patient satisfaction compared to previous treatments (p<0.00002). In contrast, electromotive intravesical lidocaine was insufficient for 3 of 6 transurethral prostatic resections. The cost per patient was about $146 Cdn less with electromotive intravesical lidocaine than with conventional general/spinal anesthesia. CONCLUSIONS: Electromotive intravesical lidocaine may be a safe, effective and affordable form of anesthesia for the ambulatory care of patients requiring transurethral bladder biopsy, resection or fulguration with a potential for cost savings.

Aged↗
PubMed1998

Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. Canadian Urologic Oncology Group.

BACKGROUND: Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo. METHODS: Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment. RESULTS: A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52). CONCLUSIONS: No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.

Adjuvants, Immunologic↗
PubMed1998

Liarozole--a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Liarozole Study Group.

OBJECTIVES: To compare the efficacy of oral liarozole, the first retinoic acid metabolism-blocking agent (RAMBA) to be developed as differentiation therapy for human solid tumors, with that of cyproterone acetate (CPA), an antiandrogen for the treatment of metastatic prostate cancer. Liarozole promotes differentiation of cancer cells by increasing the intratumoral levels of retinoic acid. METHODS: A total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy entered a Phase III international multicenter study (recruitment from February 1992 to August 1994) comparing liarozole (300 mg two times daily) with CPA (100 mg two times daily). RESULTS: Accounting for differences in baseline prognostic factors, the adjusted hazard ratio for survival was 0.74 in favor of liarozole (P = 0.039), indicating a 26% lower risk of death than in patients treated with CPA. Median crude (unadjusted) survival time was the same in the liarozole group as in the CPA group (10.3 months). More patients showed a PSA response (at least 50% reduction in PSA from baseline) when treated with liarozole (20%) than with CPA (4%) (P < 0.001). Prostate-specific antigen (PSA) responders had a median survival benefit of 10 months over nonresponders, irrespective of treatment (hazard ratio 0.43; P = 0.0018). PSA response was apparent within 3 months in approximately 90% of patients who responded. Pain improved more in the liarozole group than in the CPA group (P = 0.03). PSA responders had lower median pain scores than nonresponders (1.7 versus 2.5) and better quality of life (median Functional Living Index-Cancer score 108 versus 98) at end point, ie, treatment discontinuation, as well as throughout the treatment period. Among the most frequently occurring adverse events in the liarozole group were dry skin (51% of patients), pruritus (25%), rash (16%), nail disorders (16%), and hair loss (15%). These adverse events were generally mild to moderate in severity and did not affect the overall quality of life score. There were no detectable effects of either treatment on vital signs such as blood pressure, heart rate, electrocardiogram, and body weight. CONCLUSIONS: Liarozole is superior to CPA in terms of PSA response, PSA progression, and survival, and is capable of maintaining patients' quality of life. The observed adverse events were mild to moderate in nature. These results show that liarozole is a possible treatment option after first-line endocrine therapy has failed.

Aged↗
PubMed1998

The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index.

OBJECTIVE: To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. PATIENTS AND METHODS: The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. CONCLUSION: A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.

Adult↗
PubMed1998

Quebec prostate cancer mortality dropped in 1996.

OBJECTIVE: To monitor incidence and mortality rates of prostate cancer in the province of Quebec. DESIGN: Population-based incidence and mortality trends. SETTING: Entire population of the province of Quebec between 1979 and 1996. MAIN OUTCOME MEASURES: Age-standardized incidence rates and mortality for prostate cancer. RESULTS: Prostate cancer mortality increased regularly until 1989, were stable between 1989 and 1995 and dropped in 1996 by 15%. Incidence rates increased steadily from 1989 until 1993 by an average of 9% per year. CONCLUSION: The rise in incidence is due to the increasing use of prostate specific antigen as a screening test for prostate cancer. The reasons for the reduction in prostate cancer mortality are unknown but are likely to reflect improved treatment modalities.

Age Factors↗
PubMed1998

Dietary fat and advanced prostate cancer.

PURPOSE: We identify the dietary factors, particularly fat intake, associated with advanced prostate cancer. MATERIALS AND METHODS: We performed a case series analysis restricted to prostate cancer cases recruited in a hospital based, case control study evaluating the influence of diet on the development of prostate cancer. Patients eligible for study inclusion were 45 years old or older with prostate cancer who had been hospitalized for initial surgical treatment or radiotherapy between October 1990 and December 1992 at 1 of 8 hospitals in the Quebec City area. A diet history questionnaire was administered to 427 patients with prostate cancer of whom 384 (90%) had completed a reliable questionnaire, including 142 with advanced and 242 with local stages I and II disease. Logistic regression analysis was used to evaluate the associations between dietary intake and advanced prostate cancer. Odds ratios and trend odds ratios were adjusted for patient age, energy intake, method of cancer detection and cancer treatment. RESULTS: There was a moderate, not statistically significant relation to total fat (trend odds ratio 1.15, confidence interval [CI] 0.95 to 1.39). Cases in the highest quartile of saturated fat consumption had a statistically significant odds ratio of 2.15 (CI 1.14 to 4.04). In addition, the relation increased proportionally and significantly with saturated fat intake (trend odds ratio 1.24, CI 1.02 to 1.51). Inverse associations of borderline significance were observed between advanced cancer, and polyunsaturated fat (trend odds ratio 0.88, CI 0.73 to 1.07) and linoleic acid intake (trend odds ratio 0.86, CI 0.71 to 1.04). A positive trend was observed for total animal fat intake (trend odds ratio 1.20, CI 0.99 to 1.46), while a negative trend was noted for total vegetable fat intake (trend odds ratio 0.84, CI 0.70 to 1.01). CONCLUSIONS: This study suggests an association between saturated fat consumption and prostate cancer progression. If cohort studies performed on patients with local prostate cancer confirm these results, dietary fat intake modification may be a promising intervention to prevent prostate cancer progression.

Aged↗
PubMed1998

Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer. National Cancer Institute Bladder Tumor Marker Network.

A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed. Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was > or =20% of tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer.

Biomarkers, Tumor↗
PubMed1997

Influence of spatial configuration on the expression of carcinoembryonic antigen and mucin antigens in human bladder cancer.

CEA and cellular mucin antigens have been recognized as potential targets for specific immunotherapy and are frequently expressed in bladder cancer. We studied the coordinated expression of a bladder cancer-associated CEA glycoform and of the mucins MUC1, MUC2 and MAUB under various growth conditions in the MGH-U3 bladder-cancer cell line. CEA and MUC2 mRNAs and proteins were detected in nude mouse tumors and spheroids but not in monolayer cultures. Expression of MAUB and bladder-cancer CEA also was induced according to spatial configuration of cells. MUC1 was always expressed under various growth conditions, but its glycosylation was modulated: in spheroids and mostly in tumor cells, the SM3 protein epitope was unmasked and sialyl-Tn was induced. The kinetics of modulation of MAUB and bladder-cancer CEA were different. The epitope recognized by the monoclonal antibody (MAb) 19A211 was rapidly induced in the aggregation phase of spheroid formation and rapidly lost upon plating of tumor cells, suggesting a relationship with cell contact. By contrast, MAUB induction in spheroids was delayed to the compaction phase, when cell aggregates become resistant to disruption, and loss of expression upon tumor plating occurred slowly over several culture passages. No induction of these 2 antigens was observed in the presence of differentiation agents, endothelial cell products or interferon-gamma, but it occurred when MGH-U3 cells were cultured at high density on extracellular matrix. Our results suggest that CEA and mucin antigen expression in bladder cancer is modulated by the spatial configuration of cells.

Animals↗
PubMed1997

Biochemical analysis of a bladder-cancer-associated mucin: structural features and epitope characterization.

Three monoclonal antibodies (mAbs), M344, M300 and M75, were shown to define a unique tumour-associated antigen (TAA) of superficial bladder tumours. The antigenic determinants are expressed on a very-high-molecular-mass component and, in about 50% of the positive samples, one determinant is also detected on a 62 kDa molecular species, observed only under reducing conditions. The objectives of the present study were to characterize further this TAA by analysing (1) the biochemical nature of the epitopes recognized by the three mAbs, and (2) the biochemical and structural features of the molecule bearing them. The antigenicity was resistant to heat denaturation, trypsin and alpha-chymotrypsin treatments but highly sensitive to papain and Pronase digestion. NaIO4 oxidation decreased reactivity to mAbs M344 and M300 but enhanced reactivity to mAb M75. The three determinants were insensitive to beta-galactosidase and alpha-L-fucosidase but were sensitive to Vibrio cholerae neuraminidase. None of the three mAbs reacted with ovine, bovine or porcine submaxillary mucins. Deglycosylation with O-glycosidase or trifluoromethanesulphonic acid completely abolished the reactivity of the mAbs whereas N-glycosidase F deglycosylation had no appreciable effect. The presence on the molecule of cryptic Gal(beta(1-3))GalNAc as a major core disaccharide was demonstrated by a heterologous sandwich assay using mAb M75 and peanut agglutinin. Thiol reduction using beta-mercaptoethanol increased mobility of the high-molecular-mass component in polyacrylamide gels. We thus conclude that mAbs M344 and M300 react with sialylated carbohydrate epitopes, and mAb M75 reacts with a partially cryptic and periodate-resistant sialylated epitope expressed on a typical secreted high-molecular-mass oligomeric mucin which we named MAUB for mucin antigen of the urinary bladder.

Animals↗
PubMed1997

Neoadjuvant hormonal therapy: the Canadian experience.

OBJECTIVE: To assess the effect of neoadjuvant combination therapy with the antiandrogen flutamide and a luteinizing-hormone-releasing hormone (LHRH) agonist administered for 3 months before radical prostatectomy, compared with surgery alone in early stage prostate cancer on histopathologic findings at surgery and serum prostate-specific antigen (PSA). METHODS: A sample of 161 randomly screened patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the antiandrogen flutamide and an LHRH agonist before radical prostatectomy. RESULTS: Neoadjuvant combination therapy before radical prostatectomy decreased cancer-positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery. A net 54% improvement of staging was observed in favor of combination therapy. Organ-confined disease, on the other hand, increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.8% increase in the incidence of organ-confined disease. No cancer was found in 6 (6.7%) prostatectomy specimens from the treated group. A close correlation was found between serum PSA at diagnosis and the stage of the disease at surgery. Upstaging increased from 30% at serum PSA values of 0 to 3.0 ng/mL up to 100% at serum PSA values above 15 ng/mL. CONCLUSIONS: Although long-term follow-up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.

Adenocarcinoma↗