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)

We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ras mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs.
 ...
PMID:Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model. 945 74

To explore the relationship between short-term effects of castration therapy and clinical response, biopsies obtained before and a week after castration therapy from 15 responding and 13 non-responding patients with prostate cancer were investigated. The biopsies were assessed for regressive morphology, apoptotic index by morphological criteria, nuclear area, and immunoreactivity (IR) for Ki-67, p53, bcl-2, bax and Fas. The index was defined as the percentage of immunoreactive cells in a tumour. Regressive morphology was observed in 14 out of 15 responding tumours after therapy, compared with 4 out of 13 non-responders (P < 0.001). Median tumour epithelial cell nuclear area and Ki-67 index decreased equally in both groups. The median apoptotic index increased from 2.6 to 3.5 after castration among responders (P < 0.05), whereas it remained at 2.8 among non-responders. p53 IR was present in three tumours before castration; after therapy p53 reactivity was seen in three additional tumours belonging to the responding group. Median bcl-2 index increased in responders from 1.5 to 10.0 (P < 0.05), and in non-responders from 0.08 to 2.7 (P < 0.05). Bax IR and Fas IR were present in all tumours before therapy and unchanged after therapy. Thus, regressive morphology and an increase in apoptotic index were related to a favourable clinical response. These data suggest that it might be possible to predict the effect of castration therapy by examining tumour biopsies shortly after treatment.
 ...
PMID:Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer. 948 28

Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.
 ...
PMID:The molecular pathology of urological malignancies. 949 53

The histological classification or typing of prostate carcinoma combined with histological grading according to Gleason or WHO with nucleolar subgrading are the most important prognostic factors in carcinoma of the prostate. Prostatic cancer is the most common malignancy in adult males and is the second-most-common cause of cancer death in the USA. The histological Gleason grade may be reduced if only a small amount of tumor tissue is present in the core needle biopsy, in contrast to the combined histological and cytological grading according to WHO with nucleolar subgrading. When there is sufficient carcinomatous tissue in the core needle biopsy, there is no difference from that in radical prostatectomy tissue, because most cases of prostatic carcinoma are highly malignant. DNA cytometry, immunohistochemical analysis with Ki67/Mib1 or molecular pathological studies with the tumor suppressor gene p53 or apoptosis suppressing oncoprotein bcl2 and the density of blood capillaries may be helpful as additional prognostic factors, but only together with the results of the primary histological section. For comparison of grading results with the international literature both grading systems should be used according to Gleason and WHO with nucleolar subgrading.
 ...
PMID:[Prognostic factors of prostatic carcinoma]. 954 41

Current dilemmas for physicians managing patients with localized prostate cancer include deciding: (1) which patients need aggressive treatment; (2) what treatment options are best for a given patient; and (3) what treatment outcomes can be expected. This article reviews our ability to prognosticate outcome (including pathological stage and disease-free survival rate) in patients with clinically localized adenocarcinoma of the prostate (AJCC, stage T1-T2. N0, M0) subsequent to analysis of several contemporary series involving patients treated with radical prostatectomy and external-beam radiation therapy. Pretherapy prostate-specific antigen (PSA) level (< or =4 ng/mL or >20 ng/mL) and Gleason score (< or =4 or > or =8) as individual variables provide independent prognostic information for only a subset of patients undergoing radical prostatectomy and external-beam radiation therapy. Pathological stage is the most powerful predictor of outcome following radical prostatectomy, and its prediction (organ-confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of clinical stage, Gleason score, and PSA level. Planned systematic biopsies also provide useful prognostic information for the prediction of pathological stage and tumor volume, as well as providing additional tissue for pathological assessment of tumor heterogeneity. Several novel markers of biological aggressiveness are associated with critical steps of the metastatic cascade (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53 tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density). Their evaluation in clinical specimens is currently being used to prognosticate outcome. Current clinical and pathological parameters provide a "ballpark" estimate of outcome for patients with clinically localized prostate cancer. Further elucidation of the critical molecular events associated with prostate cancer progression and metastasis should help in identifying molecular markers that more accurately predict the prognosis for an individual patient with clinically localized prostate cancer.
 ...
PMID:Prognostic markers in clinically localized prostate cancer. 956 75

The interracial differences of prostate cancer progression have long been documented; however, underlying molecular and cellular mechanisms remain obscure. This study focuses on the histopathologic, immunohistochemical, biochemical, and molecular characterization of prostate cancer tissues unselectively obtained from US, Chinese, and Japanese men. Histopathologic analyses indicate that 74.5% of the prostate cancers in Chinese patients were poorly differentiated, compared with 28.6 and 32.8% of the prostate cancers in US and Japanese men, respectively. These differences cannot be attributed to patient age, clinical stage of disease, or methods of tissue sampling. Furthermore, the high proportion of poorly differentiated prostate cancer tissues in the Chinese group was not related to the patients' access to medical service or their geographic origins within China. We found significantly higher levels of tumor angiogenesis (2- to 4-fold), serotonin (2- to 20-fold), and bombesin (7- to 16-fold), but not chromogranin A, in tissue specimens obtained from Chinese prostate cancer patients compared with those from US and Japanese patients. We also found marked differences in p53 protein accumulation among various ethnic groups. The p53 protein was frequently detected in prostate cancer tissue specimens from Chinese (90.2%), but less frequently in US black (3.7%), US white (17.4%), and Japanese (7.1%) men. Further analysis of 31 prostate cancer tissues from Chinese men indicated that mutational changes in the p53 gene occurred between exons 5 and 8.
 ...
PMID:Interracial comparative study of prostate cancer in the United States, China, and Japan. 958 65

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavidin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or = 8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P < 0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.
 ...
PMID:Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis. 958 63

Experiments have been performed to clarify whether LHRH agonists might decrease growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were injected s.c. with the human androgen-independent prostate tumor DU 145 cells; osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were simultaneously implanted under the skin. Treatment with LHRH-A induced a significant decrease in tumor growth up to the end of the treatment. In subsequent experiment, minipumps releasing LHRH-A were implanted in nude mice either 7 or 14 days after cell inoculation. When the treatment was started 7 days after inoculation of the cells, tumor growth was significantly decreased up to 28 days; thereafter, tumor volume remained lower than in controls, although not significantly. When LHRH-A was administered beginning 14 days after cell inoculation, tumor growth was not significantly affected at any time interval considered. LHRH-A did not appear to induce apoptosis in DU 145 cells, at least on the basis of the apoptotic index and immunohistochemical staining of the p53 protein. On the other hand, treatment with LHRH-A was accompanied by a significant decrease of the concentration of epidermal growth factor receptors in DU 145 prostate cancer specimens. Our results show that the LHRH agonist used significantly inhibits the growth of DU 145 androgen-independent prostate tumor xenografts in nude mice.
 ...
PMID:Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude mice. 959 Jan 26

Prostate cancer progresses from a localized disease to a widely disseminated malignancy. Each step along this progression pathway involves multiple genetic alterations that impart a survival advantage to the tumor cell over its normal counterparts and may confer resistance to therapy. Because metastatic prostate cancer is one of the most therapy-resistant human neoplasms, we studied the expression of certain molecular determinants of drug resistance in the context of tumor progression. Paraffin-embedded formalin-fixed resected prostates were chosen based on Gleason grade and surgical stage. Immunohistochemistry was used to detect the expression of multidrug resistance protein (MRP), topoisomerase II alpha, p53, glutathione S-transferase pi, Bcl-2, and P-glycoprotein in these specimens. We found that all of the proteins were expressed in resected prostate except for P-glycoprotein. The expression of MRP, topoisomerase II alpha, p53, and Bcl-2 increased with the Gleason grade. In addition, the expression of MRP, topoisomerase II alpha, and p53 increased with the surgical stage. In contrast, the glutathione S-transferase pi and Bcl-2 expression decreased with the increasing surgical stage. Stage was the strongest indicator of protein expression. These results suggest that drug resistance gene products are expressed in prostate cancer at the time of surgical resection. Thus, although the emergence of the "pan-resistance" phenotype in prostate cancer may partly be a function of the selection pressure exerted by therapeutic interventions, certain determinants of chemoresistance may be caused by genetic changes accompanying tumorigenesis.
 ...
PMID:The expression of drug resistance gene products during the progression of human prostate cancer. 962 55

Diagnosis of prostate cancer has increased over the last few years both in localized and in more advanced stages. At present, several groups are working in the search and evaluation of alternative tumoral markers as the current ones do not cover all the Urologist's needs. In this context, a number of studies on the mutation of the tumour suppressor gen p53 in both localized and metastatic prostate cancer are being carried out. When a noxa acts on the DNA, protein p53 inhibits the cell cycle allowing the repair systems to operate and, if the damage is significant enough, cell apoptosis. The loss of this control mechanism secondary to the synthesis of anomalous proteins can result in the proliferation of neoplastic cells. A revision of the most representative papers in the literature is presented here, addressing the surrounding controversy and the resulting future possibilities.
 ...
PMID:[Current status of p53 tumor suppressor gene as a possible molecular marker of cancer of the prostate]. 965 41


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