PubMed Health⌕ Search

Biomedical subjects

J Morote

Publications and source records attributed to J Morote.

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

Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma and their association with metastasis.

Prostate carcinoma (PC) is the second leading cause of cancer death in men in the western world. Although the role of oncogenes and growth factors in prostate carcinoma is still unclear, overexpression of the epidermal growth factor receptor (erbB-1) and the proto-oncogene erbB-2 have been reported in prostate tumors, and erbB-2 related to poor prognosis and distant metastasis. Recent allelotyping studies in prostate cancer have shown chromosomal gains in 7p and 17q, regions where erbB-1 and erbB-2 are localized respectively, although no direct evidence of an increased gene copy number of either erbB-1 or erbB-2 has been reported. To address this question, we analyzed 20 benign prostatic hyperplasia (BPH) samples and 36 samples of metastatic and non-metastatic PC by means of semiquantitative PCR. Thus, 64% (11/17) and 52% (10/19) of metastatic and non-metastatic tumors respectively showed gains of the relative genomic content of erbB-1 and an association of erbB-1 with prostate cancer but not with metastasis. Additionally, 41% (7/17) of metastatic samples showed gains of erbB-2 genomic content, suggesting an association of erbB-2 with metastasis and poor prognosis (p<0.005). No gains of erbB-1 or erbB-2 genomic content were detected in the BPH samples.

Aged↗
PubMed1999

[Influence of prostatic intraepithelial neoplasia on blood levels of PSA and free PSA percentage].

OBJECTIVE: To analyze the influence of prostatic intra-epithelial neoplasia (PIN) on serum total PSA levels and free PSA percentage. MATERIAL AND METHODS: Total and free PSA concentrations (IRMA Tandem and Tandem free PSA, Hybritech Inc) were determined in 349 patients with normal DRE and PSA greater than 4 ng/ml, undergoing prostatic biopsy by sextant and in 81 patients with prostate cancer in clinical stage T1c N0 M0 undergoing radical prostatectomy. In the group of patients undergoing prostatic biopsy, benign hyperplasia was diagnosed in 284 (81.6%) patients, 234 (82.4%) were PIN free, 41 (14.4%) with low grade PIN and 9 (3.2%) with high grade PIN. Cancer was diagnosed in 65 patients (18.6%), 30 of whom (46.2%) had associated high grade PIN. High grade PIN was detected in 62 (76.5%) patients in the group undergoing radical prostatectomy. RESULTS: No statistically significant differences were detected among total PSA and free PSA percentage serum concentrations relative to the detection of associated PIN, regardless of its degree, in patients undergoing prostatic biopsy. Cancer detection was the single most significant contributing variable. In patients undergoing radical prostatectomy, high degree PIN did not influence significantly. The greatest contribution in this group was the pathological stage. CONCLUSIONS: PSA serum concentration and PSA percentage are not influenced by the existence of PIN. High degree PIN is strongly associated to cancer. Accordingly, repeat biopsies are warranted in any patient presenting such lesions.

Adult↗
PubMed1998

Over-expression of epidermal growth factor receptor and c-erbB2/neu but not of int-2 genes in benign prostatic hyperplasia by means of semi-quantitative PCR.

It is well established that activation of cellular genes may trigger uncontrolled cell growth and cancer development. Previous reports suggest that the epidermal growth factor receptor (EGFr), c-erbB2/neu and int-2, fibroblast growth factor-3, may be implicated in the development of benign prostatic hyperplasia (BPH). Using the polymerase chain reaction technique, we have assessed the amplification and expression of these molecular markers in 30 prostate samples from patients with BPH as well as from 5 normal donors. We detected mRNA over-expression of EGFr and c-erbB2/neu in 36% and 63%, respectively, of the BPH samples, but no gene amplification was found. No amplification or over-expression of int-2 was detected in any of the samples analyzed, suggesting that int-2 is not involved in BPH. Our results thus suggest a role for EGFr and c-erbB2/neu but not for int-2 in the development of BPH.

Aged↗
PubMed1998

Androgen-independent basal cell re-epithelialization, c-erbB-2 mRNA expression and androgen-dependent EGFr mRNA expression in benign prostatic hyperplasia explant cultures treated with finasteride.

We have analyzed the effects of the 5alpha-reductase inhibitor, finasteride (MK906), on the mRNA expression of the epidermal growth factor receptor and c-erbB-2 genes, in benign prostatic hyperplasia explant cultures treated with testosterone and with testosterone plus finasteride. A decrease of the epithelial cell content and an androgen-independent basal cell re-epithelialization was observed during the first 10 days of culture, suggesting a role of basal cells as stem cells involved in androgen-independent epithelial regeneration. Using a semi-quantitative reverse transcription polymerase chain reaction technique, we observed a significant decrease in expression of the epidermal growth factor receptor in the cultures treated with finasteride whereas no effect of finasteride on c-erbB-2 transcription was detected, although the expression of both genes was increased by dihydrotestosterone.

Cholestenone 5 alpha-Reductase↗
PubMed1997

Measurement of free PSA in the diagnosis and staging of prostate cancer.

The purpose of this study was to analyze the role of total prostate-specific-antigen (PSA) and free-PSA levels in the diagnosis and clinical staging of prostate cancer. We determined total-PSA serum concentration and free-PSA percentage in 352 patients, 234 with benign prostatic hyperplasia (BPH) and 118 with prostate cancer. Clinical stage of patients with prostate cancer was T1 N0 M0 in 17, T2 N0 M0 in 27, T3-4 N0 M0 in 34 and T1-4 N0-3 M0-1 in 40. Median total-PSA serum concentration was 3.1 ng/ml in patients with BPH and 26.9 ng/ml in patients with prostate cancer, p < 0.0001. Median free-PSA level was 16.7% in patients with BPH and 8.1% in patients with prostate cancer, p < 0.0001. A cutpoint of 4.0 ng/ml detected 96.6% of the prostate cancer, but the percent rate of negative biopsies was 42.1%. For a free-PSA level of 25% in patients with total PSA greater than 4.0 ng/ml, the sensitivity was 97.4%, and the decrease in negative biopsies was 21%. Median total-PSA serum concentration in patients with prostate cancer according to clinical stage was 8.9 ng/ml for T1 N0 M0, 12.9 ng/ml for T2 N0 M0, 29.9 ng/ml for T3-4 N0 M0 and 317 ng/ml for T1-4 N1-3 M0-1, p < 0.001. Median free-PSA levels were 10.1%, 8.1%, 8.4% and 6.1% respectively, p > 0.05. According to the Gleason score, median total-PSA serum concentration was 10.6 ng/ml in patients between 2 and 4, 22.3 ng/ml between 5 and 7 and 77.0 ng/ml between 8 and 10, p < 0.05. Free PSA levels were 7.7%, 8.7% and 6.6% respectively, p > 0.05. Determination of percentage of free PSA appears to be a helpful method for enhancing the specificity of total PSA. A cutpoint of 25% could detect more than 95% of prostate cancers and avoid 21% of negative biopsies in patients with total PSA above 4.0 ng/ml. However, this parameter does not provide additional information about the clinical staging of prostate cancer.

Biopsy↗
PubMed1997

Comparison of percent free prostate specific antigen and prostate specific antigen density as methods to enhance prostate specific antigen specificity in early prostate cancer detection in men with normal rectal examination and prostate specific antigen between 4.1 and 10 ng./ml.

PURPOSE: We analyzed the behavior of prostate specific antigen (PSA) density and percent free PSA to enhance the specificity of PSA in the early diagnosis of prostate cancer in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. MATERIALS AND METHODS: PSA serum level, PSA density and percent free PSA were analyzed in 74 men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. All men underwent systematic prostate biopsy, and the diagnosis was benign prostate hyperplasia in 52 and prostate cancer in 22. Furthermore, we determined the decrease in unnecessary biopsies and the cancer detection rate using 0.10 versus 0.15 as cut points for PSA density, and 20 versus 25 as cut points for percent free PSA. RESULTS: In patients with benign prostatic hyperplasia and prostate cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml. (p > 0.05), median prostate volume was 50 and 37 cc (p < 0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and median percent free PSA was 18.9 and 10.1 (p < 0.005). Using PSA density cut points of 0.15 and 0.10, the decrease in negative biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%, respectively. However, using percent free PSA cut points of 20 and 25, the decrease in negative biopsies was 36.5 and 26.9% with a sensitivity of 77.3 and 95.5%, respectively. CONCLUSIONS: Although both methods could minimize unnecessary biopsies in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective since transrectal ultrasound was not required. In this small series of symptomatic patients a percent free PSA cut point of 25 could detect at least 95% of prostate cancers and decrease 26.9% of negative biopsies.

Aged↗
PubMed1996

Prostate carcinoma staging. Clinical utility of bone alkaline phosphatase in addition to prostate specific antigen.

BACKGROUND: Biochemical markers of bone disease have been of interest as part of the investigation of prostate carcinoma and the monitoring of skeletal involvement. Bone isoenzyme of the alkaline phosphatase (BAP) is an indicator of the metabolism of the osteoblasts. An immunoradioanalyses with two monoclonal antibodies in sandwich was developed, allowing an accurate measurement of BAP concentration. The goal of the current study was to compare the clinical performance of BAP and prostate specific antigen (PSA) in patients with untreated prostate carcinoma and to determine whether or not BAP can provide valuable additional information to PSA regarding the degree of skeletal extension in patients with prostate carcinoma. METHODS: BAP and PSA serum concentrations were determined in 140 newly diagnosed prostate carcinoma patients (72 M0 and 68 M1-4). The efficiency of both markers in the prediction of positive bone scans was studied as well as the relationship observed between the concentrations of the two markers and the degree of skeletal involvement. To investigate the potential utility of BAP and PSA in eliminating the need for a bone scan, the negative predictive values for different cutoff points for both markers were calculated. RESULTS: BAP was more efficient than PSA in the prediction of positive bone scans and its level was significantly related to the magnitude of skeletal involvement whereas PSA was only able to distinguish between M0 and M1-4 groups of patients. The highest predictive value for a bone scan result was found for BAP cutoff values between 20 and 30 ng/mL, leading to negative and positive predictive values of 92.6% and 98.2%, respectively. The combination of BAP and PSA both set at a 20 ng/ mL cutoff value yielded a negative predictive value of 100% and the combination of BAP and PSA at 30 ng/mL and 20 ng/mL cutoff values, respectively, increased the positive predictive value to 98.5%. CONCLUSIONS: This study suggests that BAP could be a complementary marker to PSA in the diagnosis of bone disease in patients with prostate carcinoma. Its clinical utility could result in important cost saving implications, eliminating bone scan when PSA ranges from 10 to 20 ng/mL because the predictive negative value of PSA < 20 ng/mL and BAP < 20 ng/mL is 100% in this series. In addition, it could provide useful clinical information regarding the degree of skeletal involvement.

Adult↗
PubMed1996

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Actuarial Analysis↗
PubMed1996

Clinical efficacy of bone alkaline phosphatase and prostate specific antigen in the diagnosis of bone metastasis in prostate cancer.

PURPOSE: We investigated the usefulness of bone alkaline phosphatase isoenzyme and prostate specific antigen (PSA) determined by radioimmunoassay to predict bone scan evidence of metastasis in newly diagnosed untreated and treated prostate cancer. MATERIALS AND METHODS: We analyzed bone alkaline enzyme concentrations in 350 men, including 150 controls, 100 with benign prostatic hyperplasia and 100 with prostate cancer (52 with stages T1 to 4, M0 and 48 with stages T1 to 4, M1 to 4). We also analyzed bone alkaline phosphatase enzyme concentrations in 61 stages T1 to 4, M0 prostate cancer cases during followup after radical prostatectomy or hormonal therapy, and 17 had clinical progression (9 with local, 5 with lymph node and 3 with bone metastases). Simultaneously, we analyzed PSA concentrations. RESULTS: Average bone alkaline phosphatase enzyme levels were 12, 11.1 and 10.0 ng./ml. in the control, benign prostatic hyperplasia and stage M0 prostate cancer groups, respectively (p not significant), and 83.2 ng./ml. in patients with stage M1 to 4 disease (p<0.001). Considering that to diagnose bone metastasis the cutoff for bone alkaline phosphatase enzyme and PSA is 30 ng./ml. and 100 ng./ml., respectively, clinical effectiveness was 93.7% and 81.8%, respectively. Finally, measurement of both substances at the same time increased clinical effectiveness to 97.9%. During followup a bone alkaline phosphatase enzyme level that becomes greater than 30 ng./ml. (0% in the local and lymphatic progression groups, and 100% in the bone metastasis group) indicates the need to perform a bone scan. CONCLUSIONS: We recommend the clinical use of bone alkaline phosphatase enzyme determined by radioimmunoassay and PSA measurement for the diagnosis of bone metastases and progression of prostate cancer because of the good sensitivity and specificity.

Aged↗
PubMed1995

[Final results of complete hormone blockade versus monotherapy in prostatic metastatic cancer. PSA implications].

Of 102 patients with metastatic prostate cancer, 52 were treated with orchidectomy and 50 with CHB; 22 of these received a LHRH analog + Flutamide and 28 orchidectomy + Flutamide. No differences were seen in either arm in terms of age (69.9 vs 70.2 years) or initial PSA (493.3 vs 486.5 ng/ml) variables. After three months treatment, CHB achieved a decrease of PSA higher than monotherapy (52.9 vs 34.5 ng/ml) p<0.01 as well as minimum PSA level during follow-up (41.2 vs 17.5 ng/ml) (p<0.001). Initial clinical response rates were higher in the group treated with complete blockade (42.3% vs 52%) (p=n.s.). Overall, no significant differences were seen between the actuarial curves of biological progression, clinical progression and survival, with expected mean values of 13 vs 12, 14 vs 15 and 34 vs 28 months, respectively. However, when survival was considered as a function of bone disease dissemination, a greater survival rate was seen in patients with minimal M1 disease (p<0.05), and there were no differences between the M2 and M3 arms.

Actuarial Analysis↗
PubMed1994

[Prostate-specific antigen as an evaluation method in the treatment of hormone-refractory cancer of the prostate].

Out of 62 patients with hormone-refractory metastatic prostate cancer, 34 received rescue treatment with estramustine phosphate and 28 received non-steroidal symptomatic treatment. All patients undergoing symptomatic treatment experienced increased PSA levels while in 16 (47%) patients treated with estramustine phosphate, PSA decreased between 13-96%. In 11 cases (32.3%) the decline in PSA was higher than 50%. In 5 (14.7%) the decline was lower than 50% and in 18 cases (53%) PSA levels were increased. SCR rate was 82%, 60% and 6% respectively while OCR were 36.4%., 0% and 0% respectively. No clinical response was seen in patients undergoing symptomatic treatment. A decline in PSA levels higher than 50% 12 weeks after treatment appears to be a "good prognosis" factor related to the best clinical response rates and survival.

Estramustine↗
PubMed1994

[The concept of biologic progression in metastatic cancer of the prostate hormonally treated].

A total of 110 patients with hormone-treated metastatic prostate cancer were monitored quarterly with serial PSA determinations. At the first control, 6 patients had progressed clinically, 5 of which had decreased PSA ranging between 9-77%. After a period of response, 69 patients progressed clinically, of which 1 showed no elevation of PSA levels, 14 showed progression concurrent with PSA increase, and 54 showed a period of gradual elevation of PSA over a range of 2-31 months. The probability of biological progression when the first rise occurred ranged between 72-96%, which after a second increase ranged between 92-100%, and all patients with three consecutive increases progressed clinically.

Androgen Antagonists↗
PubMed1992

Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy.

BACKGROUND: A Phase II trial with a new regimen of methotrexate, carboplatin, and vinblastine (M-CAVI) was conducted for patients with bladder cancer who could not receive cisplatin-based chemotherapy. METHODS: Treatment consisted of methotrexate (30 mg/m2) on days 1, 15, and 22; carboplatin (300 mg/m2) on day 2; and vinblastine (3 mg/m2) on days 2, 15, and 22, scheduled at 28-day intervals. The dosage of carboplatin was adjusted for creatinine clearance. Twenty-five patients with metastatic (n = 9) or locally advanced or locoregional bladder cancer with a poor prognosis (n = 16) were treated with M-CAVI. Fifteen patients had abnormal serum creatinine levels, 4 had a low performance status, 3 had cardiac disease, and 3 were older than 70 years old. RESULTS: Among 23 patients assessable for clinical response, the response rate was 48%. The median duration of response for metastatic disease was 7 months. Among nine patients assessable for pathologic response, there were two complete responses and three partial responses. The toxic effects have been moderate. CONCLUSIONS: M-CAVI is an active and well-tolerated regimen that can be used in patients with bladder cancer who are ineligible to receive cisplatin-based chemotherapy.

Adult↗
PubMed1992

[Clinical course of hormone refractory cancer of the prostate].

Analysis of the clinical progression of 61 patients with prostate cancer undergoing hormone therapy. PSA allowed early detection in 86.9% cases. In 25 patients no rescue treatment was instituted, and 36 patients were treated with estramustine phosphate resulting in decreased PSA levels in 58% and objective response in 36%. Of these, 82% showed decreased PSA levels for over six months. Survival rate was higher in respondent, treated patients and comparable in non-respondents, treated versus non treated patients.

Acid Phosphatase↗
PubMed1992

[Can we do without bone gammagraphy in the staging of prostatic cancer?].

Correlation between findings on bone gammagraphy and PSA levels in 144 patients with untreated prostate cancer are analyzed. With prevalence of metastatic disease in 57.6% cases and considering the predictive cut value of metastasis to be 20 ng/ml, there were positive and negative predictive values of 64.9% and 73.9%, with a diagnostic confidence of 66.6%. We conclude that bone gammagraphy is essential for staging prostate cancer even in patients with PSA below 20 ng/ml.

Bone Neoplasms↗