Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The benzothiophene antiestrogen, raloxifene (LY156758), has selective estrogen pharmacological antagonist activity in rats. The PAIII rat prostatic adenocarcinoma model was used to evaluate the effects of this agent on the lymphatic and pulmonary metastasis and survival in tumor-bearing male Lobund-Wistar (LW) rats. Raloxifene was inactive against colony formation of PAIII cells in vitro. Similarly, following subcutaneous (s.c.) implantation of 10(6) PAIII cells in the tail, s.c. administration of raloxifene (2.0, 10.0, or 20.0 mg/kg/day) for 30 days failed to demonstrate cytoreductive activity against primary tumor growth in the tail. However, in these same animals, raloxifene administration produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximal responses = 89% and 81% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by raloxifene treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (P < 0.05) reduced by raloxifene administration in a dose-related manner (maximal reduction = 97% from control values). In these animals, maximal regression of 20% for ventral prostate and 21% for seminal vesicle were also seen after raloxifene administration (P < 0.05 for both). Coadministration of E2B and raloxifene had no consistent antagonistic effect upon the antitumor responses produced by raloxifene. Raloxifene (40.0 mg/kg/day for 28 days) produced marked decreases in PAIII metastasis in the lymphatic and pulmonary components. Continued administration of the compound produced significant (P < 0.05) extension of survival of PAIII-bearing rats. Further studies are needed to define the maximal antitumor efficacy and the mechanism of action of raloxifene in urogenital solid tumor animal models. These data support the contention that raloxifene represents a class of active antimetastatic agents with potential efficacy in the treatment of hormone-insensitive human prostatic cancer.
 ...
PMID:Raloxifene (LY156758) produces antimetastatic responses and extends survival in the PAIII rat prostatic adenocarcinoma model. 747 89

The clinical and pathologic staging of prostate cancer involves determination of the anatomic extent and burden of tumor based on the best available data. Two major classification schemes are currently used: the modified American system and the TNM system [primary tumor (T), regional lymph node (N), and metastases (M)]. Both systems stratify patients according to the method of tumor detection, separating nonpalpable "incidental" prostate cancers detected during transurethral resection for clinically benign prostatic hyperplasia (BPH) and palpable cancers detected by digital rectal examination. These staging systems also recognize nonpalpable tumors detected by an elevated serum prostate-specific antigen (PSA) level or an abnormal transrectal ultrasound image. Current staging is limited by a significant level of clinical understaging (up to 59%, in our experience) and overstaging (up to 5%) according to comparison with pathologic examination of resected specimens. Proposed improvements in staging include preoperative systematic sextant biopsies to assess tumor volume, volume-based prognostic index, and a multiple prognostic index. In this report, we evaluate the current aspects of clinical and pathologic staging of prostate cancer with emphasis on the early stages in which there is the greatest chance of cure.
 ...
PMID:Staging of prostate cancer. 750 5

To elucidate the outcome for patients with stage D1 (N1 to N3, M0) prostate cancer we reviewed 179 patients with lymphadenectomy proved pelvic nodal metastases who underwent immediate androgen ablation as the only initial treatment. With a median followup of 43 months, the 5 and 8-year actuarial rates of freedom from disease progression were 55% and 25%, respectively, and the median interval to disease progression was 67 months. The 5 and 8-year survival rates were 85% and 57%, respectively. Median survival after disease progression was 36 months. Local and distant disease progression was equally important. At 5 and 8 years the incidence of local progression was 32% and 51%, respectively, while metastatic rates at the same intervals wer 22% and 44%, respectively. Multivariate regression revealed that tumor grade and transurethral resection in preoperative stage C disease correlated with disease progression. Pretreatment prostate specific antigen (PSA) levels were not predictive of outcome. The fact that transurethral resection predicted for local as well as distant failure suggests that the procedure selects for rather than aggravates adverse disease. Posttreatment PSA levels were a sensitive index of response to treatment and of subsequent outcome. All patients who failed to achieve undetectable PSA levels had relapse by 8 years, whereas those whose levels became undetectable experienced only a 5% incidence of disease progression. These data show that androgen ablation alone is not curative for node positive disease but is associated with significant disease control and good short-term (5-year) survival. The primary tumor is an important source of androgen insensitive cells and comprehensive treatment strategies for this stage of disease require attention to the primary tumor as well as microscopic metastases.
 ...
PMID:Early androgen ablation for stage D1 (N1 to N3, M0) prostate cancer: prognostic variables and outcome. 815 81

In search of biomarkers that predict of human prostate cancer progression, we hypothesized that these markers must be expressed in prostatic epithelial cells during multi-step prostate carcinogenesis. Since both genetic and epigenetic factors have been implicated in human prostate cancer development, two osseous-metastatic experimental models were developed in our laboratory, one based on gene transfection and the other on stromal-epithelial interaction studies. In the genetic model, PC-3 cells transfected with point-mutated c-erbB-2/neu oncogene subsequently acquired the potential to metastasize from the prostate to soft tissues and the skeleton. In the epigenetic model, sublines derived from the parental androgen-dependent LNCaP cell line metastasized from the primary tumor to the lymph node and bone. Cells with known lineage relationships were cloned from both the primary and the metastatic tumors and were characterized extensively using cellular, biochemical, immunohistochemical, and molecular techniques. Relevant stage-specific biomarkers associated with prostate cancer progression in these two models were defined and used to evaluate human prostate tissues obtained from the clinic. In this communication, we focused our discussion on the potential importance of c-erbB-2/neu oncogene, vimentin, hepatocyte growth factor/scatter factor and its receptor, c-met oncogene, tumor angiogenesis and neuroendocrine factors as biomarkers for human prostate cancer progression.
 ...
PMID:Biomarkers associated with prostate cancer progression. 752 53

Due to problems with primary tumor cell culture, conventional cytogenetics has yielded little insightful information on chromosomal alterations in prostate cancer. The primary aim of this study was to define the ability of comparative genomic hybridization (CGH) to detect and map genetic deletions in prostate tumors. A secondary aim was to apply multiple assays to individual tumors as a means of deciphering the mechanisms of genetic alterations in prostate cancer. CGH results were compared with allelic imbalance measurements at 29 distinct loci on chromosome 8 in 18 specimens (17 malignant and 1 benign). CGH detected no changes in cases where all informative PCR/RFLP loci were retained and detected all p arm deletions consisting of at least two loci. We estimate that in this study, the smallest deletions detected by CGH were approximately 20-30 cM. Physical mapping of subchromosomal arm deletions by CGH correlated well with allelic imbalance mapping by PCR/RFLP: The data agreed at 88% of loci on 8p and 92% of loci on 8q. Fluorescence in situ hybridization (FISH) with multiple centromere probes and DNA content flow cytometry (FCM) also was performed on selected specimens. FISH revealed two cases of chromosome 8 aneusomy. In these two cases and three others, CGH showed simultaneous p arm deletion and q arm gain, suggesting isochromosome 8q formation. Together, these data suggested that, simple chromosomal aberrations were responsible for allelic losses on 8p and allelic gains on 8q in a significant number of prostate tumors. We also used CGH to examine relative DNA sequence copy number throughout the genome. Changes frequently associated with 8p loss include gains of 8q and losses of 13q, 16p, 16q, 17p, 17q, 20q, and Y. Cases with 8p loss exhibited five times the number of alterations as did cases without 8p loss.
 ...
PMID:Comparative genomic hybridization, allelic imbalance, and fluorescence in situ hybridization on chromosome 8 in prostate cancer. 753 Apr 84

Prostate cancer with marked neuroendocrine (NE) differentiation belongs to the hormone resistant carcinomas. We report the development of TSH-secreting small cell prostate cancer (SCPC) from high grade adenocarcinoma (Gleason score 8) with an elevated number of chromogranin A positive cells located in benign structures adjacent to the cancer. Conversion to SCPC was followed-up during 4 years. The initial adenocarcinoma exerted a stronger positivity for PAP than for PSA (respective staining indexes, Sls, 2.2 and 1.8, maximum staining 3.0). In the developed SCPC, 2 cell subpopulations that were derived from epithelial cells were found (positive stain for EMA and CEA, respectively) and from one of them originated CEA-positive liver metastases. Blood CEA and NSE levels were elevated in SCPC (284 ng/ml and 24.5 ng/ml). However, blood TPS level which reflects proliferation of epithelial cells was within the normal range. The development of a << pure >> sarcomatoid prostatic tumor from adenocarcinoma with 2 areas of similar differentiation grades (Gleason score 7 and 9-10) that initially differ in staining for PSA and PAP (SIs for PSA were 1.2 and 0.02 and for PAP were 1.6 and 0.02, respectively) was followed-up during 4 years of treatment with Estracyt. Adenocarcinoma tissue specimens was slightly CEA-positive. The disappearance of lower grade adenocarcinoma during treatment was accompanied by the development of sarcomatoid areas that were 100% vimentin positive. In the last year of follow-up the primary tumor was composed only of vimentin positive sarcomatoid cells with a slight positivity for Chromogranin A, NSE and ACTH. In parallel, normal serum PSA and PAP values and elevated CEA and NSE serotests (12.6 ng/ml and 24.7 ng/ml, respectively) were found. Blood TPS level was at the upper limit of the normal range. Scintigraphy revealed extensive liver metastases. The recorded data indicate (i) extremely poor prognoses associated with high grade adenocarcinomas that demonstrate stronger immunohistochemical positivity for PAP than that for PSA (ii), chromogranin A positive cells in benign structures adjacent to the cancer as a possible paracrine promoter of SCPC from poorly differentiated adenocarcinoma, and (iii) a high degree of heterogeneity of both SCPC and sarcomatoid prostatic neoplasms with some evidence for definite links (EMA and CEA) to secretory epithelial cells.
 ...
PMID:Immunohistochemical staining and serotest markers during development of a sarcomatoid and small cell prostate tumor. 784 May 15

In order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327-MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene-modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327-MatLyLu tumors.
 ...
PMID:An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer. 820 23

Among the patients who were examined with bone scintigraphy between April 1985 and March 1991, there were 27 patients whose initial clinical manifestation was bone metastasis and who were surveyed for the primary tumor site. The primary tumor site could be identified in 20 patients (74%), consisting of 9 patients with lung cancer, 3 with prostate cancer, 3 with hepatoma, 2 with renal cancer, and one each with thyroid cancer, adrenal cancer, and pleural malignant mesothelioma. In 17 of the 20 patients, the primary site had been detected within two months after presentation. Examinations which were helpful in identifying the primary site included chest radiography, sputum cytology, abdominal sonography, serum prostatic acid phosphatase level and pathologic examination of biopsy specimens. 99mTc-PMT scintigraphy was useful in the diagnosis of the hepatoma when accumulation was observed at the metastatic sites. In 2 patients, lung cancer had been recognized using follow-up chest radiography 3 and 6 months after presentation, respectively. One patient was diagnosed at autopsy as having adrenal cancer. In 7 patients the primary site remains unknown. Histology examination of the biopsy specimen performed in 6 of these patients revealed 4 to be adenocarcinoma and 2 undifferentiated carcinoma. The average survival period of the 17 patients who died was 9.5 months. Four patients are alive, and the outcome in the remaining 6 could not be determined.
 ...
PMID:[Survey for primary tumor site in patients with initial clinical presentation of bone metastasis]. 823 Aug 25

To assess the mechanisms and prognostic significance of seminal vesicle involvement (SVI) by prostatic adenocarcinoma, we analyzed 312 radical prostatectomy specimens obtained from patients with T1-T3 prostate cancer. Detailed pathological examination demonstrated three patterns of SVI. Type I involvement was direct spread along the ejaculatory duct complex into the seminal vesicles. Type II involvement was spread outside of the prostate, through the capsule, and then into the seminal vesicle. Type III involvement was characterized by the finding of isolated deposits of cancer in the seminal vesicle with no contiguous primary cancer in the prostate. We found SVI in 64 patients (21%), who have been followed for a mean of 31 months (range 1-101). A defining criterion for progression was clinically apparent local or distant recurrence or a postoperative serum prostate specific antigen (PSA) > or = 0.4 ng/ml (Hybritech). Type I SVI was found in 17 (26%), Type II in 21 (33%), and Type III in 8 (13%) cases. In 18 patients (28%), the pattern of SVI appeared to be a combination of types I and II (categorized as Type I+II). Type III (isolated metastasis) SVI was associated with significantly smaller cancers (median, 3.13 vs. 6.7 cc; p < 0.0005) and fewer positive margins (0 vs. 32%; p = 0.05) than in other types. Type II SVI, with direct extension through the capsule, was associated with a significantly higher risk of lymph node metastasis (8 vs. 33%; p < 0.05). When patients with lymph node metastases were excluded, there was a trend toward a more favorable prognosis (p = 0.09) for patients with type III SVI than with other types. Overall, patients with type III SVI had a progression-free survival rate similar to that of 83 patients with extracapsular extension without SVI. We conclude that the prognostic significance of SVI may not be uniformly ominous; instead, it may depend on the specific mechanism of involvement and the pathologic features of the primary tumor.
 ...
PMID:The mechanisms and prognostic significance of seminal vesicle involvement by prostate cancer. 823 32

The study was carried out in order to investigate the possibility of tumor reduction in prostate cancer patients. As a reduction of the primary tumor was observed with hormonal treatment and complete response of soft tissue tumor markers with Mitomycin C, this combined treatment was given in seven patients to evaluate if it was able to down-stage those cases which were thought to be incurable (T3N1-2M0/T4N0-2M0). Although the clinical evaluation suggested a significant down-staging, the explorative lymphadenectomy was unable to confirm this. The proposed treatment is able to reduce the tumor bulk significantly of the primary cancer as well as of its metastases; progression during the treatment was not seen.
 ...
PMID:Down-staging prostate cancer. Is it possible by androgen depletion and Mitomycin C therapy? 829 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>