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Biomedical subjects

E J Pontes

Publications and source records attributed to E J Pontes.

At least 19 recordsLinked to original sources

Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy.

An inverse association has been observed between dietary intake of lycopene and the risk of prostate cancer. We investigated the effects of lycopene supplementation in patients with prostate cancer. Twenty-six men with newly diagnosed, clinically localized (14 T(1) and 12 T(2)) prostate cancer were randomly assigned to receive 15 mg of lycopene (n = 15) twice daily or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of differentiation and apoptosis were assessed by Western blot analysis on benign and malignant parts of the prostate gland. Prostatectomy specimens were entirely embedded, step-sectioned, and evaluated for pathological stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. Eleven (73%) subjects in the intervention group and two (18%) subjects in the control group had no involvement of surgical margins and/or extra-prostatic tissues with cancer (P = 0.02). Twelve (84%) subjects in the lycopene group and five (45%) subjects in the control group had tumors <4 ml in size (P = 0.22). Diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia was present in 10 (67%) subjects in the intervention group and in 11 (100%) subjects in the control group (P = 0.05). Plasma prostate-specific antigen levels decreased by 18% in the intervention group, whereas they increased by 14% in the control group (P = 0.25). Expression of connexin 43 in cancerous prostate tissue was 0.63 +/- 0.19 absorbance in the lycopene group compared with 0.25 +/- 0.08 in the control group (P = 0.13). Expression of bcl-2 and bax did not differ significantly between the two study groups. IGF-1 levels decreased in both groups (P = 0.0002 and P = 0.0003, respectively). The results suggest that lycopene supplementation may decrease the growth of prostate cancer. However, no firm conclusions can be drawn at this time because of the small sample size.

Administration, Oral↗

[Comparison among patients considered candidates for radical prostatectomy in academic institutes in different countries].

OBJECTIVE: Radical prostatectomy is performed in potentially curable prostatic cancers, but surgical indication might somehow depend on the idiosyncrasies of a population. Herein we compare the characteristics of patients undergoing radical prostatectomy in teaching University Hospitals of different countries. METHODS: We conducted a retrospective review on 250 consecutive patients who underwent radical prostatectomy before January 1997 in five teaching University Hospitals in Europe (Spain, Sweden, Switzerland, Turkey) and the United States (Detroit, MI). Clinicopathological data were recorded and compared, and a questionnaire investigated whether patient and physician attitudes towards surgery differed. RESULTS: The number of surgeries per month at each institution ranged from 0.9 to 10 and the proportion of newly diagnosed patients that undergo surgery from 0.14 to 0.36. The Kruskal-Wallis test revealed both median age and preoperative prostate-specific antigen (PSA) levels were different between groups. Similarly, despite standardized surgery and histologic work-up, differences in the detection of extracapsular invasion and the rate of detectable PSA after surgery were observed between institutions. Diagnosis in the Swedish and Swiss groups was more often based on digital rectal examination, while the rest were more confident with transrectal ultrasound. Doctors at some institutions were more inclined to recommend radical surgery, either by not mentioning or disapproving other therapeutic strategies. The proportion of patients who said they would elect surgery again ranged from 72% to 92%, and the proportion of doctors who said they would perform surgery again ranged from 78% to 100%. Patients' and doctors' degree of satisfaction with the decision made were also different. CONCLUSIONS: (i) Candidates for radical prostatectomy in teaching hospitals of several countries are different. Might therefore have practical implications on the design of clinical trials and the interpretation of the results of treatment. (ii) Patient and physician acceptance of surgery varies according to countries and is more established firm in those countries where it is more frequently performed.

Adult↗

Predicting the need for adjuvant systemic therapy in patients receiving postprostatectomy irradiation.

OBJECTIVES: This study was initiated to determine if clinical, pathologic, or biochemical variables available in patients receiving postprostatectomy irradiation could be predictive of treatment outcomes, including the need for subsequent systemic therapy. METHODS: Between January 1992 and January 1995, 50 patients received external beam irradiation for a nonzero or rising postprostatectomy prostate-specific antigen (PSA) level. The median PSA values preoperatively and preradiation were 24 and 2.7 ng/mL, respectively. At the time of treatment, no patient had evidence of disseminated disease. The patients received a combination of axial and noncoplanar irradiation to an average total dose of 65 Gy at 1.8 Gy fractions. Univariate analysis and multivariate logistic regression were performed to identify factors predictive of outcome. RESULTS: Treatment was well tolerated with no grade 3 or higher gastrointestinal or genitourinary complications. A decline in the serum PSA during irradiation occurred in 82% of the patients. During radiation, 13 patients (26%) had a complete response (PSA less than 0.05 ng/mL), 56% had a partial response, and 18% had a rise in their PSA level. With a median follow-up of 16 months, 50% of all patients have an undetectable level of PSA. Twenty-six percent of patients have had evidence of biochemical progression. Seventeen percent of responding patients and 67% of nonresponders have evidence of progression (P= 0.002). On univariate analysis, other significant prognostic factors included clinical stage (P < 0.01), the preradiation PSA level (P < 0.05), and N stage (P < 0.01). On stepwise multivariate logistic analysis, a predictive model was generated from which treatment outcome could be predicted with 80% accuracy (percent correct classification) and an 85% sensitivity. CONCLUSIONS: The outcome of patients with an elevated postprostatectomy PSA level who receive irradiation can be accurately predicted using a combination of clinical stage, preradiation PSA value, Gleason score, and the response to treatment. In this way, patients who do not require additional treatment (that is, hormonal) will avoid the unnecessary cost and toxicity.

Aged↗

[Prognosis prediction in patients with transitional cell carcinoma of the urinary bladder].

OBJECTIVES: Many attempts have been made during decades to identify factors predictive of prognosis in patients with transitional cell carcinoma (TCC) of the bladder. The present study attempts to determine the predictive factors in a large series of patients with long follow-up homogeneously treated at three institutions from 1983 to 1992. METHODS: The clinical and histological factors with presumed prognostic value were retrospectively evaluated in a series of 331 patients with a mean follow-up of 7.2 years, and a study of survival was performed. RESULTS: Univariate analysis showed tumor stage, growth pattern, grade, size, coexisting dysplasia, histologic type, topography of the lesion and patient age are useful parameters for the prediction of prognosis. The Cox analysis revealed tumor stage is the most important prognostic variable (Beta = 1.23, p < .001), followed by growth pattern as determined by the presence or absence of a papillary phenotype (Beta = 1.18, p < .001), tumor size (Beta = .98, p < .001), WHO modified histologic grading considering persistence or loss of cell polarity (Beta = .73, p < .01), tumor location (Beta = .48, p < .05), and histology (presence or absence of phenotypes other than pure TCC, Beta = .45, p < .05). Coexisting dysplasia, tumor multiplicity, age and sex did not independently influence survival. CONCLUSION: Despite the advancements in the field of molecular biology relative to prognostic markers in bladder cancer, the conventional morphological parameters and tumor stage continue to be the main source of prognostic information in clinical practice.

Adult↗

Rearrangement of chromosome 3 in renal cell carcinoma.

Rearrangements involving chromosome #3 were detected in 8 of 12 nonfamilial renal cell carcinomas. These results suggest that rearrangement of chromosome #3 is associated with the genesis and progression of a subclass of human renal cell carcinoma.

Adult↗

Percutaneous management of upper tract transitional cell carcinoma.

Conservative (nephron-sparing) surgery for transitional cell carcinoma of the upper tract generally has entailed variations of partial nephrectomy or open pyelotomy with excision and fulguration of tumor. We report on a patient in whom percutaneous technology was used successfully to manage transitional cell carcinoma of the lower infundibulum after other treatment options had been exhausted.

Aged↗

A comparison of estrogen and androgen receptor levels in human prostatic tissue from patients with non-metastatic and metastatic carcinoma and benign prostatic hyperplasia.

Estrogen receptors (ER, N = 72) and androgen receptors (AR, N = 33) were determined by high pressure liquid chromatography (HPLC) in 72 human prostatic tissues obtained at prostatectomy, and exploratory statistical analyses of the resulting data were performed. To facilitate use of these data as well as other pertinent information from the patient charts, a program for a comparatively large data base was implemented on a Wang minicomputer. The median values of cytosolic AR in the four cancer stages examined were statistically different from each other (P = 0.01), with AR increasing from stages A through D. Even though ER differences between the four stages were not significant (P = 0.13), there was a trend, in the data examined, for median ER values to decrease with stages B through D. On the other hand, median BPH values for both ER and AR were found to lie mid-scale compared with the respective cancer stages, leading to the conclusion that receptor measurements probably cannot distinguish between CA and BPH in human prostatic tissue, at least as measured by competitive binding techniques.

Binding, Competitive↗

Flow cytometric analysis of DNA aneuploidy in primary and metastatic human solid tumors.

DNA histograms were measured by flow cytometry for 656 human solid tumors (365 primary and 291 metastatic). The proportion of aneuploid cells in cell suspensions obtained by mechanical disaggregation was significantly higher than those obtained after enzymatic disaggregation (collagenase + DNAse) of the same tumor. A strong correlation was observed between the values of DNA-indices measured after staining with propidium iodide and with 4',-6-diamidino-2-phenylindole (r = 0.97). Aneuploid cells were observed in 430 tumors (66%); 30 of these had two aneuploid stemlines, and two had three aneuploid stemlines. The overall frequency of aneuploidy was 61% among primary and 71% among metastatic tumors. The median value of the DNA index was 1.67 for 224 primary aneuploid tumors and 1.68 for 206 metastatic aneuploid tumors. For most diseases, the largest proportion of aneuploid primary and metastatic tumors had DNA-indices in the hypertriploid region. No major differences in frequency and degree of aneuploidy was observed between primary and metastatic tumors. For carcinomas of the bladder and prostate, frequency of aneuploidy was higher among poorly differentiated, than among moderately and well-differentiated tumors. For carcinomas of the breast and for sarcomas, tumors with DNA-indices of greater than 2.0 were observed mostly in the poorly differentiated group. For patients with carcinomas of the bladder and prostate most tumors at earlier stages of disease were diploid; whereas most tumors at later stages of disease were aneuploid. For patients with carcinomas of the ovary, colon, and kidney, no relationship between stage of disease and aneuploidy was evident.

Aneuploidy↗

Correlation of estrogen and androgen receptor status in prostatic disease measured by high pressure liquid chromatography.

To further characterize human prostatic estrogen receptors (ER) determined by high pressure liquid chromatography (HPLC), we checked our procedure by which we nullify estrogen binders (including testosterone binding globulin, TeBG) other than ER by preincubation of cytosols with dihydrotestosterone (DHT). We also showed that the ER exhibited ligand specificity and that ER is present in BPH nuclear extract at 10-fold its concentration in the corresponding cytosols. Of seven prostates with localized cancer determined preoperatively, only 3 showed localization; ER concentration in the cancer parts was lower than in the corresponding surrounding BPH. A total of 22 specimens were evaluated for ER and androgen receptors (AR). Statistically, AR had higher values than ER but there was no correlation between the corresponding AR and ER for each tissue.

Adenocarcinoma↗

A micromethod for the measurement of estrogen receptors using high pressure liquid chromatography.

Adequate sample size has been one of the difficulties encountered in routine determination of estrogen receptors in prostatic disease. The recent commercial availability of protein analysis columns for use with high pressure liquid chromatography (HPLC) equipment has made the achievement of a considerable reduction in sample size feasible. We present a method for determination of ER which includes the use of 16 alpha-125-iodo-estradiol ( [125I]-E2) of 1600 Ci/mmol specific activity, the use of G-25 column chromatography, followed by fractionation by HPLC and finally relation of the fmol specifically bound to mg protein measured in the HPLC peak. Data obtained upon determination of ER in the immature rat uterine model system are given to show consistent recoveries, ligand specificity, saturability, inhibition, and commonly accepted KD and n values for this system. Also, in a pilot study on 13 samples from human prostatectomies, the utility of the HPLC technique for ER measurement in that tissue using single point analysis is demonstrated. For comparison, all receptor determinations reported were also made using conventional methods.

Animals↗

The use of serum isoenzymes of alkaline and acid phosphatase as possible quantitative markers of tumor load in prostate cancer.

The tumor burden of 98 patients with metastatic prostatic cancer was compared longitudinally with the activities of bone (BAP) and liver isoenzymes (LAP) of alkaline phosphatase, total acid phosphatase (AcP), and prostate-specific acid phosphatase (PAP). A quantitative association between these enzyme markers and the tumor mass was suggested by comparing the enzymes with 1) both the treatment response and the estimation of metastasis by radionuclide bone scanning; 2) metastasis based upon radiographic evidence. In addition, an apparent extensive pretreatment bone tumor load was predictive for an elevated BAP activity, which was also a suggestive poor prognosis as previously reported. An elevation of PAP, in contrast to AcP, may precede the clinical disease progression in some patients. Data presented in this report have indicated that the levels of these enzymes compared well with the extent of tumor involvement and therefore may be considered suitable as adjuvant and even quantitative biochemical markers of bone and liver metastasis.

Acid Phosphatase↗

Studies of the growth of a murine renal cell carcinoma and its metastatic patterns.

Metastatic lung tumor cells from a murine renal cell adenocarcinoma were implanted in Blab/C mice for 12 transfer generations. Survival time of the implanted mice was observed to decrease from 48 days to 28 days. The incidence of lung metastases increased from 40% to 90%. These studies suggest a selection process under the terms of the experiment that has resulted in a change in the metastatic potential of the primary tumor and its serial passage of metastases. The results are compatible with current concepts regarding cell selection in this cancer state but do not, at the present time, precisely define how this is achieved. Appropriate and selective studies are ongoing to address this important issue.

Adenocarcinoma↗

Double-antibody immunoenzyme assay for human prostatic acid phosphatase.

We compare the double-antibody radioimmunoassay (RIA) and immunoenzyme assay (IEA) for measuring the concentration of prostatic acid phosphatase in human serum. Experimental details and assay performance of the two methods are outlined. Mean values for 385 normal persons were 1.02 (SD 1.32) microgram/L by IEA, 2.69 (SD 1.8) microgram/L by RIA. Results of the two methods was highly correlated [r = 0.9813, y(RIA) = 0.35 x (IEA) + 0.42, p < 0.001]. If we choose x- + 2 SD as the normal range, 3-10% false positives were seen.

Acid Phosphatase↗

Purification and characterization of human prostatic acid phosphatase.

Human prostatic acid phosphatase (orthophosphoric monoester phosphohydrase, EC 3.1.3.2) is purified to homogeneity by standard procedures which include CM-Sephadex, Con A affinity chromatography and gel filtration. The purified enzyme is antigenically specific and has a M.W. of 100,000 with subunit M.W. of 48,000. However, the enzyme exhibited charge heterogeneity. Two major electrophoretic or chromatographic isozymic forms of PAP were separated by DEAE-Sephadex chromatography and their immunochemical identity was studied by immunodiffusion before and after the neuraminidase digestion. Quantitative precipitin and inhibition experiments showed immunological identity of the two chromatographic isozymes. Immunologic specificity of this enzyme resides on the protein moiety rather than the carbohydrate residue, although the latter group is mostly responsible for the charge group heterogeneity of the enzyme.

Acid Phosphatase↗