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)

A 55-year-old man with prostate cancer received a total prostatectomy. Two days after the operation, he suffered from high fever and shaking chilliness, followed by skin eruption, hypotension, diarrhea and chest pain. The results of blood bacterial culture and endotoxin were negative. Toxic shock syndrome was suspected, and the administration of vancomycin (VCM) and continuous hemodialysis-filtration (CHDF) were performed. The steroid pulse therapy for adult respiratory distress syndrome (ARDS) and the treatments for DIC were also done, and they were effective. The desquamation of the extremity was observed on 10 days after the operation. MRSA was finally identified from pus discharge of the operation wound 13 days after the operation. The prevention and treatments for toxic shock syndrome were discussed.
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PMID:[Toxic shock syndrome due to methicillin resistant staphylococcus aureus (MRSA) after total prostatectomy]. 1184 39

Since the last in a series of childbirth education classes discusses contraception, educators must know about various family planning methods. Oral contraceptives (OCs) comprise combined OCs, phasic OCs, and minipills. Combined OCs inhibit secretion of gonadotropin-releasing hormone, which in turn keeps the follicle-stimulating hormone from inducing the ovarian follicle to grow and keeps luteinizing hormones from activating ovulation. They also thicken cervical mucus. Minipills also thicken cervical mucus and render the endometrium unreceptive to fertilized egg implantation. They do not always inhibit ovulation, however. OCs can induce side effects, such as nausea, hypertension, increased risk of atherosclerosis, and fatigue. The IUD prevents pregnancy either by inhibiting implantation of a fertilized egg or by an inflammatory reaction of the endometrium resulting in a release of macrophages which may destroy sperm. The no-longer-produced Dalkon Shield IUD increased the risk of pelvic inflammatory disease and damaged the reputation of other IUDs. Rare IUD complications are uterine perforation, salpingitis, tubal scarring, pelvic inflammatory disease, and infertility. Diaphragms, cervical film, and condoms serve as barriers between the egg and sperm. The main problem with barrier methods is the increased risk of developing toxic shock syndrome. Spermicide increase the effectiveness of diaphragms, cervical caps, and condoms. Vasectomy keeps sperm from arriving at storage sites. Shortterm side effects are swelling, discomfort, and occasional rejoining of the cut ends of the vas. Research hints at a link between vasectomy and prostate cancer. Some complications of tubal ligation are urinary tract infections, accidental electrical burns, and pelvic infections. Natural family planning methods include withdrawal, the rhythm method, and the sypto-thermal method. Controversial injectable contraceptives are Depo-Provera (medroxyprogesterone acetate) and Noristerate (norethisterone enanthate).
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PMID:Birth control update for childbirth educators. 1234 29

We and others previously cloned and characterized vertebrate WNT11 orthologs, which are involved in gastrulation, neurulation, cardiogenesis, nephrogenesis, and chondrogenesis during fetal development. WNT11 orthologs activate both canonical and non-canonical WNT signaling cascades depending on the expression profile of WNT receptors, such as Frizzled family members, LRP6, ROR2, and RYK. Human WNT11 is expressed in breast cancer, gastric cancer, esophageal cancer, colorectal cancer, neuroblastoma, Ewing sarcoma, and prostate cancer. Canonical WNT signals and GATA family members are involved in WNT11 transcription during embryogenesis of model animals; however, precise mechanisms of WNT11 expression remain unclear. Here, refined integrative genomic analyses of WNT11 are carried out to elucidate the mechanisms of WNT11 transcription. The WNT11 gene was found to encode two isoforms by using alternative first exons. WNT11 isoform A (NM_004626.2 RefSeq) consists of exons 2, 3, 4, 5 and 6, whereas WNT11 isoform B consists of exons 1, 2, 3, 4, 5 and 6. We identified double TCF/LEF-binding sites within the proximal promoter regions -48-bp position from the TSS of human WNT11 isoform B and -43-bp position from the TSS of human WNT11 isoform A), and also double GATA-binding sites within intron 2 of human WNT11 gene (+933-bp and +5001-bp positions from TSS of human WNT11 isoform A). Double TCF/LEF- and double GATA-binding sites within the regulatory regions of human WNT11 gene were conserved in other mammalian WNT11 orthologs. These facts indicate that canonical WNT signals and GATA family members directly upregulate WNT11 transcription. Canonical WNT-induced WNT11 activates non-canonical WNT signaling cascades to induce cellular movement, and also activates the Ca2+-MAP3K7-NLK signaling cascade to break the canonical WNT signaling. Canonical WNT-to-WNT11 signaling loop is involved in cellular migration during embryogenesis as well as tumor invasion during carcinogenesis.
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PMID:Integrative genomic analyses of WNT11: transcriptional mechanisms based on canonical WNT signals and GATA transcription factors signaling. 1957 97

Rex1 (zfp42) was identified by our laboratory because of its reduced expression in F9 teratocarcinoma stem cells after retinoic acid (RA) treatment. The Rex1 (Zfp42) gene is currently widely used as a marker of embryonic stem cells. We compared the transcriptional regulation of the human Rex1 gene in NTera-2 (NT-2) human teratocarcinoma, normal human prostate epithelial cells (PrEC), and prostate cancer cells (PC-3) by promoter/luciferase analyses. Oct4, Sox2, Nanog, and Dax1 transcripts are expressed at higher levels in NT-2 and PrEC cells than in PC-3 cells. Co-transfection analyses showed that YY1 and Rex1 are positive regulators of hRex1 transcription in NT-2 and PrEC cells, whereas Nanog is not. Serial deletion constructs of the hRex1 promoter were created and analyzed, by which we identified a potential negative regulatory site that is located between -1 and -0.4 kb of the hRex1 promoter. We also delineated regions of the hRex1 promoter between -0.4 kb and the TSS that, when mutated, reduced transcriptional activation; these are putative Rex1 binding sites. Mutation of a putative Rex1 binding site in electrophoretic mobility shift assays (EMSA) resulted in reduced protein binding. Taken together, our results indicate that hRex1 binds to the hRex1 promoter region at -298 bp and positively regulates hRex1 transcription, but that this regulation is lost in PC-3 human prostate cancer cells. This lack of positive transcriptional regulation by the hRex1 protein may be responsible for the lack of Rex1 expression in PC-3 prostate cancer cells.
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PMID:Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells. 2023 20

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes' upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2'-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients.
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PMID:Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer. 2412 49

Aberrant DNA methylation at promoters is often linked to tumorigenesis. But many aspects of DNA methylation remain unexplored, including the individual roles of distal and gene body methylation, as well as their collaborative roles with promoter methylation. Here we performed a MBD-seq analysis on prostate specimens classified into low, high, and very high risk group based on Gleason score and TNM stages. We identified gene sets with differential methylation regions (DMRs) in Distal, TSS, gene body and TES. To understand the collaborative roles, TSS was compared with the other three DMRs, resulted in 12 groups of genes with collaborative differential methylation patterns (CDMPs). We found several groups of genes that show opposite methylation patterns in Distal and Genic regions compared to TSS region, and in general they are differentially expressed genes (DEGs) in tumors in TCGA RNA-seq data. IPA (Ingenuity Pathway Analysis) reveals AR/TP53 signaling network to be a major signaling pathway, and survival analysis indicates genes subsets significantly associated with prostate cancer recurrence. Our results suggest that DNA methylation in Distal and Genic regions also plays critical roles in contributing to prostate tumorigenesis, and may act either positively or negatively with TSSs to alter gene regulation in tumors.
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PMID:Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis. 2692 43

EMT (epithelial-mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/ paracrine manner.
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PMID:Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell. 2756 88