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

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Nebulous language, distrust, and dogma confound spiritual aspects of cancer care. However, existential well being is an important determinant of quality of life: finding meaning and purpose make suffering more tolerable. The case presented is of a patient who experienced "losing God" as a Hodgkin's disease survivor with metastatic prostate cancer and severe coronary artery disease. His caregivers were able to provide the sense of community in which he could re-establish his faith. Health care providers do not have to be religious in order to help patients to deal with a spiritual crisis. The clinical skills of compassion need to be deployed to diagnose and respond to spiritual suffering. Acknowledging and addressing anger or guilt, common sources of suffering, are essential to adjustment. Simply being there for the patient and being open to their hurt can help resolve their spiritual crisis, a responsibility that is shared by the whole health care team.
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PMID:Losing God. 1142 76

We report a case of a 49-year-old man who presented with symptoms related to his right eye. Subsequent workup revealed carcinoma of the prostate metastatic to the uvea. On ophthalmologic evaluation, choroidal metastasis was noted. His prostate was firm on digital rectal examination, and the serum prostate-specific antigen level was 124 ng/mL. Prostate biopsy was consistent with adenocarcinoma, Gleason score 9. The patient was treated with total androgen blockade and radiation to the eye. Although his ocular lesions disappeared, the patient died of hormone-refractory disease 32 months after the diagnosis. The first case of prostate cancer metastatic to the uvea was reported more than 1 century ago; however, only a few cases have been reported subsequently. To our knowledge, we present the first published report in the urological literature of a patient in whom ocular complaints were the presenting symptoms that led to the diagnosis of prostate cancer. The urologist should be cognizant of the distinct possibility of ocular metastasis if a patient with prostate cancer presents with complaints related to the eye.
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PMID:Metastatic adenocarcinoma of the prostate to the uvea as the initial presenting symptom in a 49-year-old man. 1144 97

Identification of genes involved in the transition from androgen-dependent to androgen-independent prostate cancer is important to extend our current knowledge of the disease. Using differential display RT-PCR analysis between androgen-dependent and androgen-independent prostate cancer cells, we have identified a novel gene, designated GC109. GC109 harbours a putative Cys-His cluster, a nuclear localisation signal, a leucine zipper and a ret finger protein (rfp)-like domain. GC109 mRNA expression in normal human tissues was found not to be restricted to the prostate. However, using a variety of 15 human cancer cell lines, GC109 mRNA was preferentially expressed in androgen-dependent LNCaP-FGC, compared with androgen-independent LNCaP-LNO, DU145 and PC3 human prostate cancer cells. Finally, the GC109 gene was mapped on human chromosome 2p24. Based on its protein domain structure and chromosomal localisation, we hypothesise that GC109 may be involved in chromosomal rearrangements in prostate cancer.
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PMID:A novel gene on human chromosome 2p24 is differentially expressed between androgen-dependent and androgen-independent prostate cancer cells. 1159 95

We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER-alpha) in human breast and prostate cancer cell lines but only weakly inhibits ER-alpha activity in cervical cancer cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999). We now report that the ability of BRCA1 to repress ER-alpha activity correlates with its ability to induce down-regulation of the cellular levels of the transcriptional coactivator p300 in breast and prostate, but not in cervical cancer cells. On the other hand, BRCA1 failed to alter the expression of the CREB binding protein (CBP), the structural and functional homologue of p300, in any of these cell types. Ectopic expression of either p300 or CBP "rescued" (i.e., reversed) the BRCA1 inhibition of ER-alpha activity, whereas two other nuclear receptor coactivators, the p300/CBP-associated factor (PCAF) and the glucocorticoid receptor-interacting protein-1 (GRIP1), failed to rescue the ER-alpha activity. The rescue function mapped to the cysteine-histidine rich domain CH3, a region of p300/CBP that we found to interact directly with the conserved COOH-terminal activation domain (AF-2) of ER-alpha. p300 and ER-alpha were also found to interact in vivo and to colocalize within the nucleus in breast cancer cells. These findings suggest that the cofactors p300 and CBP modulate the ability of the BRCA1 protein to inhibit ER-alpha signaling. They further suggest that the BRCA1 inhibition of ER-alpha activity may be attributable, at least in part, to the down-regulation of p300.
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PMID:p300 Modulates the BRCA1 inhibition of estrogen receptor activity. 1178 71

The authors describe a case of high-output cardiac failure in a patient with rapidly progressing prostate cancer for which no previously described cause could be found. His new onset and increasingly worsening heart failure corresponded to the rapid spread of his prostate cancer. The authors hypothesize that a cytokine released from the neoplastic cells or the bone was responsible for the high-output cardiac failure observed in this patient. (c)2001 CHF, Inc.
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PMID:High-output cardiac failure in a patient with prostate cancer. 1182 71

In a subset of endocrine therapy-resistant prostate cancers, amino acid substitutions H874Y, T877A and T877S, which broaden ligand specificity of the ligand binding domain (LBD) of the androgen receptor (AR), have been detected. To increase our knowledge of the role of amino acid substitutions at these specific positions in prostate cancer, codons 874 and 877 were subjected to random mutagenesis. AR mutants were screened in a yeast readout system for responsiveness to 5 alpha-dihydrotestosterone, progesterone and dehydroepiandrosterone. At position 874, only the histidine to tyrosine substitution could broaden AR ligand specificity. At position 877, 4 ligand specificity broadening substitutions were found: T877A, T877S, T877C and T877G. The latter 2 were not found in prostate cancer. The AR mutants were tested in mammalian (Hep3B) cells for responsiveness to 13 different ligands. All mutants displayed their own ligand specificity spectrum. Importantly, AR(H874Y) and AR(T877A) could be activated by cortisol. According to the 3-dimensional structure of the AR LBD, T877 interacts directly with the 17 beta-hydroxyl group of androgens. All amino acid substitutions identified at position 877 had smaller side chains than the threonine in the wild-type receptor, indicating that increased space in the ligand binding pocket is important in broadened ligand specificity. Because H874 does not interact directly with the ligand, its substitution by a tyrosine is expected to change the ligand binding pocket conformation indirectly. For T877C and T877G substitutions, 2-point mutations are required, and for H874Y, T877A and T877S substitutions, only a 1-point mutation is sufficient. This most likely explains that the latter 3 have been found in prostate cancer.
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PMID:Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancer. 1211 46

Androgen blockage, with either orchiectomy or luteinizing hormone releasing hormone (LHRH) analogs combined with an antiandrogen drug, is the standard treatment for metastatic prostate cancer. Flutamide is a non-steroidal antiandrogen drug that is frequently used for total androgen blockage. We report on a 54-yr-old man with metastatic prostate cancer who developed nonoliguric acute renal failure (ARF) during treatment with flutamide. Following discontinuation of flutamide therapy, his renal functions returned to normal limits within 4 wk. After a rechallenge with flutamide, serum levels of BUN and creatinine increased again. His renal function recovered completely after the cessation of the drug for the second time. This observation confirm that ARF may be clearly attributed to flutamide therapy. Although very rare, flutamide-induced ARF should be considered.
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PMID:Flutamide-induced acute renal failure in a patient with metastatic prostate cancer. 1218 Apr 80

The androgen receptor (AR) is a ligand-dependent transcription factor that has an essential role in the normal growth, development, and maintenance of the prostate gland. The AR is part of a large family of steroid receptors that also includes the glucocorticoid, progesterone, and mineralocorticoid receptors. Steroid receptor family members share significant homology at their DNA and ligand-binding domains. However, these receptors exhibit a high degree of sequence variability at their NH(2)-terminal domain, which suggests the possibility of receptor-specific interactions with co-regulator proteins. Transcriptional co-regulators that interact with the AR may have a role in defining AR activity and may be involved in directing AR-specific responses. Here we have identified Ran-binding protein in the microtubule-organizing center (RanBPM) to be a novel AR-interacting protein by yeast two-hybrid assay and have confirmed this interaction by glutathione S-transferase- and His-tagged pull-down assays. In addition, transient overexpression of RanBPM in prostate cancer cell lines resulted in enhanced AR activity in a ligand-dependent fashion. Glucocorticoid receptor activity was also enhanced when RanBPM was overexpressed, whereas estrogen receptor activity remained unchanged. These data demonstrate that RanBPM interacts with steroid receptors to selectively modify their activity.
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PMID:RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor. 1236 45

The differential display-polymerase chain reaction technique was employed to obtain a prostate-specific approximately 300-bp cDNA fragment. On screening the human prostate-lambdagt10 library with this fragment, a full-length approximately 1.5-kb cDNA encoding for a prostate antigen, designated as human novel prostate-specific antigen (hNPSA), was found. Extensive database searches revealed that the hNPSA cDNA is a novel sequence. It has an open reading frame (ORF) of 735-bp encoding for 245 amino acids (aa), with a calculated molecular mass of approximately 27kDa. Hydrophilicity analysis of the deduced aa sequence indicated that hNPSA is a membrane-anchored peptide. Analysis for tissue-specificity by Northern blot and RT-PCR-Southern blot procedures indicated that hNPSA is specifically expressed only in human prostate. The hNPSA (ORF) was subcloned into pET22b(+) vector and expressed using the histidine-tagged gene fusion system. The recombinant (r) protein of approximately 27kDa was purified and antibodies (Ab) were raised in rabbits. The rhNPSA Ab recognized a specific protein band of approximately 35kDa in solubilized human prostate tissue and not in any of the other 10 human tissues tested in the Western blot procedure. The hNPSA expression is upregulated 2.5- to 3-fold, both at the mRNA and protein levels in androgen-dependent LNCaP cells, as compared to normal whole prostate tissue. Antisense, but not the sense, phosphothiorate-conjugated oligonucleotides based on the hNPSA cDNA sequence significantly (p<0.001) inhibited proliferation of LNCaP cells in a concentration-dependent manner. Thus, the novel hNPSA, which has prostate-specific expression and seems to be involved in carcinogenesis, may have applications in the specific diagnosis and treatment of prostate cancer.
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PMID:Novel human prostate-specific cDNA: molecular cloning, expression, and immunobiology of the recombinant protein. 1237 95

Grape seed extract (GSE), rich in the bioflavonoids commonly known as procyanidins, is one of the most commonly consumed dietary supplements in the United States because of its several health benefits. Epidemiological studies show that many prostate cancer (PCA) patients use herbal extracts as dietary supplements in addition to their prescription drugs. Accordingly, in recent years, we have focused our attention on assessing the efficacy of GSE against PCA. Our studies showed that GSE inhibits growth and induces apoptotic death of human PCA cells in culture and in nude mice. Here, we performed detailed studies to define the molecular mechanism of GSE-induced apoptosis in advanced human PCA DU145 cells. GSE treatment of cells at various doses (50-200 micro g/ml) for 12-72 h resulted in a moderate to strong apoptotic death in a dose- and time-dependent manner. In the studies assessing the apoptotic-signaling pathway induced by GSE, we observed an increase in cleaved fragments of caspases 3, 7 and 9 as well as PARP in GSE-treated cells after 48 and 72 h of treatment. Pre-treatment of cells with general caspases inhibitor, z-Val-Ala-Asp(OMe)-FMK or caspase 3-like proteases inhibitor [z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-FMK], almost completely (approximately 90%) inhibited the GSE-induced apoptotic cell death. In a later case, GSE-induced caspase-3 activity was completely inhibited. Selective caspase 9 inhibitor [z-Leu-Glu(OMe)-His-Asp(OMe)-FMK] showed only partial inhibition of GSE-induced apoptosis whereas GSE-induced protease activity of caspase 9 was completely inhibited. Upstream of caspase cascade, GSE showed disappearance of mitochondrial membrane potential and an increase in cytochrome c release in cytosol. Together, these results suggest that GSE possibly causes mitochondrial damage leading to cytochrome c release in cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic death of human PCA DU145 cells. Furthermore, GSE-caused caspase 3-mediated apoptosis also involves other pathway(s) including caspase 9 activation.
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PMID:Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release. 1241 35


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