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 clinical course of prostate cancer (PCa), the most common cancer in Swedish men, is highly variable and difficult to predict. Consequently, there is an urgent need to distinguish tumours with a high risk of progression from those with a low risk. To investigate the prognostic implications of proliferation and apoptosis, two important processes in tumor biology, immunoreactivity for biomarkers associated with these processes was assessed, quantified in indexes, and related to cause-specific survival (CSS). A consecutive series of 186 men presenting with voiding symptoms and PCa were treated with transurethral resection and deferred endocrine therapy. After 13-21 years follow-up, 43% of these men had died of prostate cancer. In a subgroup of men with localised disease at the time of diagnosis, 27% succumbed to the disease. Immunoreactivity for p53 protein, indicative of a defective p53 function, predicted shorter CSS in univariate (52 vs 123 months, p < 0.0001), but not in multivariate analysis. Mean index for the apoptosis blocking bcl-2 protein was higher in foci of prostatic intraepithelial neoplasia, a putative precursor to PCa, than in manifest cancer areas (79 vs 12, p < 0.0001). This indicates that bcl-2 may be involved in early tumourigenesis. No prognostic value was found for the bcl-2 index. A high index for the proliferation marker Ki-67 predicted shorter CSS in univariate (53 vs 132 months p < 0.0001) and in multivariate analysis. To test if p53 is predictive for clinical radioresistance, as suggested by experimental models, p53 immunoreactivity was investigated in biopsies obtained before radical radiotherapy in an unrelated series of 60 PCa patients. Patients with p53 reactive tumours had longer CSS, indicating that p53 is not treatment-predictive for radiotherapy in Pca. Core biopsies were obtained before and a week after castration therapy in patients with advanced PCa. According to the serum prostate specific antigen (PSA) level 3 months after therapy, 15 responding tumours and 13 non-responding tumours were selected. Regressive morphology was seen in 14/15 responders after castration therapy, compared with 4/13 non-responders. Median apoptotic index increased significantly after castration therapy for responders (from 2.6 to 3.5, p < 0.05) whereas it was 2.8 before and after therapy in non-responders. This indicates that subsequent clinical response can be predicted by the induction of regressive morphology and an increase in apoptotic index. In conclusion, immunoreactivity for Ki-67 appeared to be a putative prognostic factor in PCa, whereas the prognostic value of p53 and bcl-2 was dubious. p53 immunoreactivity did not appear to be predictive of radioresistance in PCa. Cellular response in biopsies shortly after castration therapy might be treatment-predictive.
 ...
PMID:Prognostic factors in prostate cancer. 924 5

Within a few weeks, if therapy of the hormone sensitive, advanced prostate cancer (PCa) is sufficient, there will be a PSA-decrease to testify to the regression of the PCa. Free-PSA (f-PSA) is used for the differential diagnosis of the PCa. Values under 25% f-PSA in proportion to complete-PSA show the possibility of the existence of a Pca. The aim of the work was to study the behavior of f-PSA under hormonal ablation. Initial PSA and f-PSA was examined (RIA) in 76 patients (average age = 72.8 yrs. old) with advanced PCa. (metastases) proven by bone scintigraphy and/or computed tomography. During hormonal therapy (LHRH-agonists) monthly PSA and f-PSA abundance were examined. The percent amount of f-PSA was calculated and documented for at least 6 months. The initial PSA-values were 43.6 +/- 17.3, the f-PSA were 13.4% +/- 8.9. Under antihormonal therapy PSA decreased (while f-PSA increased) and after a period of 1 month the values were 27.4 +/- 14.9 (17.4% +/- 12.3), after 3 months 18.1 +/- 11.3 (24.5% +/- 9.9), after 6 months 7.9 +/- 6.8 (26.1 +/- 10.6). During the 6 months of hormonal ablation PSA-values continuously declined, while, after the first 3 months, f-PSA-values showed a behavior similar to benign hyperplasia of prostate. The therapeutic efficiency of the antihormonal therapy is clearly shown through f-PSA and PSA. There are no timely advantages between the two markers. Further investigations will show whether hormone insensitive PCa can be recognized quicker through f-PSA than from an increase in PSA.
 ...
PMID:The behavior of prostate specific antigen (PSA) and free-PSA (f-PSA) under antihormonal therapy. 1132 55

We previously showed that mRNA encoding TARP (T cell receptor gamma chain alternate reading frame protein) is exclusively expressed in the prostate in males and is up-regulated by androgen in LNCaP cells, an androgen-sensitive prostate cancer cell line. We have now developed an anti-TARP monoclonal antibody named TP1, and show that TARP protein is up-regulated by androgen in both LNCaP and MDA-PCa-2b cells. We used TP1 to determine the subcellular localization of TARP by Western blotting following subcellular fractionation and immunocytochemistry. Both methods showed that TARP is localized in the mitochondria of LNCaP cells, MDA-PCa-2b cells, and PC-3 cells transfected with a TARP-expressing plasmid. We also transfected a plasmid encoding TARP fused to green fluorescent protein into LNCaP, MDA-Pca-2b, and PC-3 cells and confirmed its specific mitochondrial localization in living cells. Fractionation of mitochondria shows that TARP is located in the outer mitochondrial membrane. Immunohistochemistry using a human prostate cancer sample showed that TP1 reacted in a dot-like cytoplasmic pattern consistent with the presence of TARP in mitochondria. These data demonstrate that TARP is the first prostate-specific protein localizing in mitochondria and indicate that TARP, an androgen-regulated protein, may act on mitochondria to carry out its biological functions.
 ...
PMID:The T cell receptor gamma chain alternate reading frame protein (TARP), a prostate-specific protein localized in mitochondria. 1515 Feb 60

Six microsomal population of estradiol and androgen receptors have been characterized in human benign prostatic hypertrophy (BPH) and prostate cancer (PCa). Estradiol receptor (ER) and androgen receptors (AR) were extracted using 0.6 M KCL and determined by the dextran-coated charcoal method. ER and AR levels were smaller in BPH plasma membranes (PM) than in Pca cases. For functions 3, 4, 6, the ER values in PCa were 25-38% less with regard to BPH ER values. Whereas in PCa, AR values obtained in all fractions were higher when compared to BPH AR values. In benign prostatic hypertrophy and prostatic cancer, ER and AR levels were significantly higher in the nuclear fraction. In the nuclear fraction, ER and AR levels in BPH and PCa were significantly different. The subcellular distribution of AR and ER in BPH and PCa constitutes a reservation mechanism and processing a receptors for their continued growth.
 ...
PMID:Prostatic cancer/benign prostatic hypertrophy. Subcellular distribution of estradiol/androgen receptors. 1580 68

Prostate cancer ( PCa) is an important genitourinary malignancy with increasing morbidity and mortality. Glutathione S-transferase P1 ( GSTP1) , as a phrase- II enzyme, has an important role in the activation and detoxification of carcinogens. There is a close association between GSTP1 gene polymorphisms and the risk of Pca. GSTP1 CpG island hypermethylation can reliably distinguish Pca from benign prostatic hyperplasia( BPH) and promises to be an important molecular marker for the diagnosis of Pca. This paper summarizes the association of GSTP1 with the diagnosis and risk of Pca.
 ...
PMID:[Progress in studies of glutathione S-transferase P1 and prostate cancer]. 1720 Dec 61

Low specificity of PSA for early diagnosis of prostate cancer (PC) is the cause of search for new tests. The aim of our study was to develop the logistic regression model and estimate the value of the regression equation as a diagnostic tool for prostate cancer detection. A total of 518 male patients aged 47-83 years (mean 65.5 +/- 6.5 years) who had undergone TRUS-guided 12-core systematic transrectal prostate biopsy were included in the study. PC detection rate in our study was 43.8%. The logistic regression model with PC detection as a response and age, prostate volume, PSA, induration on DRE and hypoechoic lesion on TRUS as effects was designed. With regression equation PC probability for any patient was calculated. The regression equation was tested as a PC diagnostic tool. As the combination of model effects (chi-square 87.9; p < 0.0001; R2 = 0.124) any of the effects independently may predict prostate cancer detection. The obtained regression equation is: P(Pca) = 1/{1 + 2.718(-[-4.029 + (0.068 x AGE) + (0.022 x PSA) + (-0013 x PROSTATE VOLUME) + (0.375 x DRE) + (0.254 x TRUS)])} Accuracy (area under ROC-curve) of our regression equation as a PC detection diagnostic tool was 73%. Probability cutoff of 0.26 leads to sensitivity of 90% and specificity of 30% and eliminates 12% of unnecessary biopsies in patients with benign prostate diseases (chi-square 10.91; p < 0.0001). Thus, the obtained logistic regression equation may be used as a PC diagnostic tool in the suspects. Multicenter trial may improve regression equation diagnostic performance.
 ...
PMID:[Estimation of predictive prostate cancer probability with logistic regression equation]. 1791 53

Chemoprevention is presumably one of most effective means to combat prostate cancer (PCa). Patients usually require more than a decade to develop a clinically significant Pca, therefore, an ideal target for chemoprevention. This review will focus on recent findings of a group of naturally occurring chemicals, carotenoids, for potential use in reducing PCa risk.
 ...
PMID:Carotenoids and prostate cancer risk. 1847 40

The development of biomarkers for prostate cancer screening, detection and prognosis has greatly decreased the mortality of this disease. Recently, some new views on such biomarkers as PSMA, CK34betaE12, p63, AMACR, Pca-24, hTERT, DD3, Annexin A3 and GSTP1 methylation in prostate cancer tissue have been re-identified and investigated. Future research should focus on the combined screening of multiple biomarkers and discovery of new ones, which may possibly improve the sensitivity, specificity and accuracy of the early detection of prostate cancer.
 ...
PMID:[An update of biomarkers in prostate cancer tissue]. 2021 20

Given the important roles of miRNA in post-transcriptional regulation and its implications for cancer, characterization of miRNA facilitates us to uncover molecular mechanisms underlying the progression of androgen-independent prostate cancer (PCa). The emergence of next-generation sequencing technologies has dramatically changed the speed of all aspects of sequencing in a rapid and cost-effective fashion, which can permit an unbiased, quantitive and in-depth investigation of small RNA transcriptome. In this study, we used high-throughput Illumina sequencing to comprehensively represent the full complement of individual small RNA and to characterize miRNA expression profiles in both the androgen dependent and independent Pca cell line. At least 83 miRNAs are significantly differentially expressed, of which 41 are up-regulated and 42 are down-regulated, indicating these miRNAs may be involved in the transition of LNCaP to an androgen-independent phenotype. In addition, we have identified 43 novel miRNAs from the androgen dependent and independent PCa library and 3 of them are specific to the androgen-independent PCa. Function annotation of target genes indicated that most of these differentially expressed miRNAs tend to target genes involved in signal transduction and cell communication, epically the MAPK signaling pathway. The small RNA transcriptomes obtained in this study provide considerable insights into a better understanding of the expression and function of small RNAs in the development of androgen-independent prostate cancer.
 ...
PMID:Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing. 2115 91

Cancer stem cells (CSCs) are involved in tumorigenesis and progression of prostate cancer (PCa). Conventional anticancer therapeutics failed to eradicate CSCs, which may eventually lead to the disease relapse and metastasis. Therefore, targeting prostate CSCs may be an ideal strategy to cure PCa. Genistein is a major isoflavone constituent of soybeans and soy products, which has been shown to exhibit potent anticancer effect on many cancers. We have previously reported that genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition, suggesting that genistein may be effective against metastatic PCa. In addition, we have recently demonstrated that PCa tumorsphere cells (TCs) possess CSC properties. Here, we found that tumorsphere formation and colony formation of Pca cells were noticeably suppressed in the presence of genistein. Pretreatment of PCa TCs with genistein also suppressed tumorigenicity in vivo. Additionally, genistein treatment inhibited tumor growth of PCa TCs. Further studies showed that genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo, but also inhibited Hedgehog-Gli1 pathway, which may contribute to the anti-CSC effect of genistein in PCa TCs. Therefore, our findings demonstrated that genistein may be a dietary phytochemical with potential to target prostate CSCs.
 ...
PMID:Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway. 2248 70


1 2 3 Next >>