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)

The standard therapy for advanced prostate cancer is androgen ablation. Despite transitory responses, hormonally treated patients ultimately relapse with androgen-independent disease that is resistant to further hormonal manipulation and cytotoxic chemotherapy. To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines. We report here that elevation of intracellular cAMP markedly inhibits the growth of the hormone-refractory cell line PC-3. To examine the mechanism of cAMP action in PC-3 cells, we tested the effect of the cAMP analog dibutyryl cAMP (Bt2-cAMP) on the regulation of the potent negative growth factor transforming growth factor beta (TGF-beta). Bt2-cAMP selectively induced the secretion of TGF-beta 2 and not TGF-beta 1 by PC-3 cells. This TGF-beta 2 was shown to be bioactive by using the CCL-64 mink lung cell assay. TGF-beta 1 was not activated despite being present at 3-fold higher concentrations than TGF-beta 2. Northern analysis showed that Bt2-cAMP induced an increase in the five characteristic TGF-beta 2 transcripts and had no effect on the level of TGF-beta 1 or TGF-beta 3 transcripts. TGF-beta 2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces the expression of active TGF-beta 2 by PC-3 prostate carcinoma cells, suggesting a new approach to the treatment of prostate cancer and a new molecular mechanism of cAMP action.
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PMID:Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3. 137 3

Shortening of telomeres along with an up-regulation of telomerase is implicated in the immortality of tumor cells. Targeting either telomeres or telomerase with specific compounds has been proposed as an anticancer strategy. Because telomerase activity and telomeres are found in normal cells, telomere or telomerase targeting agents could induce side effects in normal tissues. We evaluated the effects of telomere and telomerase interactive agents in human tumor and normal cell lines to try to determine the potential side effects those agents might induce in patients. Toxicity of the G-quadruplex interactive porphyrins (TMPyP4, TMPyP2) and azidothymidine (AZT) were tested using a cell-counting technique against normal human cell lines (CRL-2115 and CRL-2120, fibroblasts; NHEK-Ad, adult keratinocytes; CCL-241, small intestinal cells; NCM 460, colonic mucosal epithelial cells) and human tumor cell lines (MDA-MB 231 and Hs 578T, breast cancer; SK-N-FI, neuroblastoma; HeLa, cervix cancer; MIA PaCa-2, pancreatic cancer; HT-29 and HCT-116, colon cancer; DU 145, prostatic cancer cell line). Telomerase activity of these cell lines was measured by a non-PCR-based conventional assay. The effects of TMPgammaP2, TMPyP4, and AZT were also evaluated against normal human bone marrow specimens, using a granulocyte-macrophage colony-forming assay (CFU-GM). AZT showed very low cytotoxic effects against normal and tumor cell lines, with the IC50 values above 200 microM. The IC50 values for TMPyP2 and TMPyP4 in normal human cell lines were in the range of 2.9-48.3 microM and 1.7-15.5 microM, respectively, whereas in tumor cell lines the IC50 values were 11.4-53 microM and 9.0-28.2 microM, respectively. Within the tissue types, keratinocytes were more sensitive to TMPyP4 than fibroblasts, and small intestinal cells were more sensitive than colonic mucosal epithelial cells. The IC50 for TMPyP2 and TMPyP4 in the normal marrow colony-forming assays were 19.3 +/- 5.1 microM and 47.9 +/-1.0 microM, respectively. In conclusion, the in vitro cytotoxicity of the telomere interactive agent TMPyP4 is comparable in human tumor and normal cell lines, which indicates that TMPyP4 could have effects on normal tissues.
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PMID:Effect of telomere and telomerase interactive agents on human tumor and normal cell lines. 1074 25

There have been no calls for reversal surgery in the aftermath of studies which point to a connection between vasectomy and increased risk of prostate cancer. Instead, doctors have been advised to continue to perform the procedure while further research takes place. 2 of the studies which identified the risk were published in 1990 in the same journal. In the first, the authors found an "unexpected" association between vasectomy and prostate cancer (a 3.5-5.3 times greater risk for vasectomized men) but postulated that an undetected bias might be the cause. In the second, a case control study of 614 men with prostate cancer revealed a 1.7 times higher overall risk which began 12 years after the surgery and increased to 2.2 times between 13 and 18 years postvasectomy. The third and fourth studies were published in the same journal in 1993. The third report, of a prospective study, followed 10,055 cancer-free vasectomized men and 37,000 similar controls for 4 years and found a 1.6 times greater risk of prostate cancer in vasectomized men which increased with age to a 1.85 times relative risk 22 years after the procedure. The fourth report, a retrospective analysis, investigated 13,124 vasectomized men and 12,392 controls and found an elevated risk of 1.56 after 10 years postvasectomy which increased to 1.89 at 20 years. Vasectomy affects the prostate gland by interrupting the normal flow of fluid from the testes through the prostate gland via the ejaculatory ducts. After vasectomy (and with aging), the prostate itself also secretes less fluid. In addition, vasectomy alters immune function which may, in turn, enhance tumor growth. It is possible that reversal surgery will prove to reduce this risk of prostate cancer.
CCL Family Found
PMID:Update on vasectomy. 1234 48

Immune thrombocytopenic purpura (ITP) occurs in 2-3% of chronic lymphocytic leukemia (CLL) patients, whereas autoimmune thrombocytopenia is very rare before the diagnosis of lymphoma. A 67-year-old patient, was admitted to our Department because of purpura on his inferior limbs. Family history revealed arterial hypertension, a previous presence of hepatitis C virus (HCV) antibodies, with no sign of liver damage. Physical examination showed purpura of inferior limbs. Laboratory analysis revealed: marked thrombocytopenia (platelet count 5000/microL); hypogammaglobulinemia (9%, immunoglobulin-IgG 634 mg/dL); presence of HCV antibody (negative HCV-RNA); low-titer anti-nuclear antibody and anti-smooth muscle antibody (1:80); positive cryoglobulin (polycolonal, IgG-IgM, cryocrit 0.5%). Abdomen ultrasound revealed a mild liver steatosis and bone marrow aspirate megakaryocytic hyperplasia. Platelet kinetics study showed a markedly reduced platelet half-life (<1 day) with evident splenic uptake. The patient was treated with steroids, intravenous Ig and immunosuppressive agent (cyclophosphamide) with only temporary effect; a splenectomy was therefore performed with a subsequent durable increase in the platelet count. Two years later, the patient underwent a prostatectomy for prostate cancer and within the pelvic nodal screening the histological examination unexpectedly revealed features of B-cell non-Hodgkin's lymphoma, type CCL/small lymphocytic lymphoma; a bone marrow aspirate showed a monotypic CD5+, CD19+, CD23+ B-cell proliferation confirming the diagnosis of CLL. Six months later, a computed tomography scan revealed multiple pathological node enlargements (1.5-3 cm), compatible with a malignant lymphoma. The marked thrombocytopenia may have been an early expression of the lymphoproliferative disease. Otherwise, the association between CLL and ITP might reflect the underlying role of HCV infection causing an immune dysregulation responsible for both pathologies.
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PMID:Association between immune thrombocytopenic purpura and chronic lymphocytic leukemia in a patient carrier of anti-hepatitis C virus antibodies. 1625 Jan 87

Inflammation has a role in prostate tumorigenesis. Recruitment of inflammatory monocytes to the tumor site is mediated by C-C chemokine ligand 2 (CCL2) through binding to its receptor CCR2. We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells and thereby promote recruitment of monocytes. Given the inhibitory effect of broccoli-derived compounds indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) on androgen-dependent pathways, we also reasoned that I3C and DIM could modulate the effect of androgen on CCL2-mediated pathways. Dihydrotestosterone was found to induce a time-dependent (0-72 hours) and concentration-dependent (0-1 nmol/L) increase in CCL2 mRNA levels in androgen-responsive human prostate cancer cells (LNCaP). This increase in CCL2 mRNA corresponded with increased secretion of CCL2 protein. The effect of dihydrotestosterone was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction of CCL2. Although dihydrotestosterone also induced TWIST1 mRNA, an epithelial-mesenchymal transition-related factor, and purported inducer of CCL2, blocking its expression with small inhibitor RNA did not inhibit dihydrotestosterone induction of CCL2 mRNA. Moreover, conditioned media from androgen-treated cells promoted human monocyte THP-1 cell migration and this effect was blocked by antibody against CCL-2. Both I3C and DIM inhibited promotional effects of dihydrotestosterone on CCL2 and migration. These results show that androgen may regulate CCL2 and promote inflammatory microenvironment in prostate tumors and that this process can be blocked by broccoli-derived compounds.
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PMID:Indole-3-carbinol and 3',3'-diindolylmethane modulate androgen's effect on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells. 2358 26

A series of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives 5, 6 and 7 were prepared starting from 6-phenyl-4-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-3-amine 3 via selective N-alkylation, followed by reaction with different primary aliphatic amines, cyclic secondary amines or l-amino acids under different set of conditions. All the synthesized compounds 5, 6 and 7 were screened for anticancer activity against four cancer cell lines such as A549-Lung cancer (CCL-185), MCF7-Breast cancer (HTB-22), DU145-Prostate cancer (HTB-81) and HeLa-Cervical cancer (CCL-2). The compounds 5i and 6e are found to have promising bioactivity at micro molar concentration.
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PMID:Synthesis and biological evaluation of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. 2406 Apr 86

Prostate cancer (PCa) is the second leading cause of cancer-related death in men globally. However, there are few sensitive biomarkers for PCa, especially those which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody microarrays allow for high-throughput and high-sensitivity detection of multiple proteins simultaneously, providing a powerful tool for biomarker screening. Here, we selected 46 patients with PCa and 42 controls with BPH, and compared the serum levels of different cytokines in PCa and BPH patients using antibody microarrays. The results indicated that serum levels of macrophage colony-stimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa pathogenesis, and thus were used as positive controls in the present study. CCL-18 is a chemokine primarily involved in recruitment of the adaptive immune system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells. Serum levels of these four cytokines could distinguish PCa from BPH with high sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC) was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as new potential serum biomarkers for PCa.
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PMID:CC chemokine ligand 18 and IGF-binding protein 6 as potential serum biomarkers for prostate cancer. 2474 38

A library of diversely stereo-oriented, highly substituted 2,6-cis piperidine derivatives were synthesized, and evaluated for their anticancer activity in cancer cells that included A549 (lung cancer, CCL-185), MCF7 (breast cancer (HTB-22), DU145 (prostate cancer (HTB-81), and HeLa (cervical cancer, CCL-2). One stereo-variant emerged as a promising candidate for further design based structure-activity studies.
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PMID:A concise diastereoselective approach to enantioenriched substituted piperidines and their in vitro cytotoxicity evaluation. 2517 18

Type 2 diabetes (T2D) is associated with worse prognosis of prostate cancer (PCa). The molecular mechanisms behind this association are still not fully understood. The aim of this study was to identify key factors, which contribute to the more aggressive PCa phenotype in patients with concurrent T2D. Therefore, we investigated benign and PCa tissue of PCa patients with and without diabetes using real time qPCR. Compared to patients without diabetes, patients with T2D showed a decreased E-cadherin/N-cadherin (CDH1/CDH2) ratio in prostate tissue, indicating a switch of epithelial-mesenchymal transition (EMT), which is a pivotal process in carcinogenesis. In addition, the gene expression levels of matrix metalloproteinases (MMPs) and CC chemokine ligands (CCLs) were higher in prostate samples of T2D patients. Next, prostate adenocarcinoma PC3 cells were treated with increasing glucose concentrations to replicate hyperglycemia in vitro. In these cells, high glucose induced expressions of MMPs and CCLs, which showed significant positive associations with the proliferation marker proliferating cell nuclear antigen (PCNA). These results indicate that in prostate tissue of men with T2D, hyperglycemia may induce EMT, increase MMP and CCL gene expressions, which in turn activate invasion and inflammatory processes accelerating the progression of PCa.
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PMID:Increased Expressions of Matrix Metalloproteinases (MMPs) in Prostate Cancer Tissues of Men with Type 2 Diabetes. 3320 9