Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIDS-related Kaposi sarcoma (AIDS-KS) is the most common malignancy associated with HIV infection, with an incidence of 10-30% of all AIDS patients. As such, there have been a large number of AIDS-KS cell strains isolated and numerous studies conducted to elucidate the mechanisms of malignancy in this disease. We have reported histological grade associated differences in the ability of AIDS-KS cell strains to proliferate under conditions of minimal growth factor supplementation, with strains derived from high grade lesions having enhanced proliferation potential. Furthermore, we found that this difference in in vitro growth characteristics was not attributed to grade associated differences in autologous growth factor release. These current investigations explored the hypothesis that grade associated growth differences could be attributed to differences in the expression of the components of the IL-6 receptor, or expression/inducibility of the pleotrophic transcription factor NF-kappa B. We determined there were no significant grade associated differences in the expression of either component (IL-6R alpha chain or gpl30) of the IL-6 receptor. However, non-lesional oral derived cell strain lysates from AIDS-KS patients (n = 4) contained significantly lower concentrations of both components of the IL-6 receptor than AIDS-KS strains (n = 8) and lower concentrations of gp-130 than normal human oral derived fibroblasts (n = 2). Comparative analysis of sera concentrations of soluble components of the IL-6 receptor did not demonstrate significant differences between HIV+/KS+ (n = 7), HIV+/KS- (n = 9) and normal (HIV-/KS-) (n = 4) populations. Further, no differences were detected in the expression of NF-kappa B in AIDS-KS cell strains (n = 5) derived from both high and low histological grade lesions as compared to nonlesional AIDS-KS cell stain (n = 1) and normal human oral derived fibroblasts (n = 2) under conditions of: constitutive/proliferative growth, sera starvation, oxidative stress, and mitogen reintroduction after sera starvation. In conclusion, these investigations have eliminated two explanations for histological grade associated differences for in vitro growth potential of AIDS-related KS cell strains and further substantiated the lack of systemic paracrine cytokine/cytokine receptor effects in AIDS-KS pathogenesis.
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PMID:Expression of interleukin-6 receptors and NF-kappa B in AIDS-related Kaposi sarcoma cell strains. 921 76

Retinoblastoma tumor suppressor protein (pRB) inhibition by tumor virus oncoproteins has been attributed to the need for these viruses to promote lytic viral nucleic acid synthesis by unscheduled entry into the S phase of the cell cycle. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a functional cyclin (vCYC) which is expressed during latency and can direct phosphorylation of pRB. We mapped the two major latent transcripts encoding vCYC, latent transcript 1 (LT1) and LT2, by cDNA sequencing, 5' rapid amplification of cDNA ends, and primer extension analyses. Both LT1 and LT2 transcripts are spliced, originate from the same start site, and encode ORF K13 (vFLIP) as well as ORF72 (vCYC). The latency-associated nuclear antigen (LANA, ORF73) is encoded by LT1 but spliced from LT2. While differential expression of the two transcripts was not found, the promoter controlling LT1/LT2 transcription is regulated in a cell cycle-dependent manner. Activities of both KSHV LT1/LT2 and huCYC D1 luciferase promoter reporters transfected into NIH 3T3 cells increase 11- and 4-fold, respectively, after release from cell cycle arrest by serum starvation. Further, vCYC and huCYC D2 mRNA levels are low in naturally infected BCBL-1 cells arrested in late G1 with L-mimosine but increase in parallel during a 24-h period after release from cell cycle arrest. Cell cycle regulation of KSHV vCYC expression mimics cellular D cyclin regulation and may maintain infected cell cycling. This is consistent with an alternative hypothesis that tumor viruses have developed specific responses to innate cellular defenses against latent virus infection that include pRB-induced cell cycle arrest.
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PMID:Characterization and cell cycle regulation of the major Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) latent genes and their promoter. 988 49

Several sexually transmitted viruses have been associated with the development of Kaposi's sarcoma (KS), a highly vascularized multi-focal neoplasm, characterized by the presence of spindle-shaped and endothelial cells, fibroblasts and macrophages. As BK virus (BKV) sequences were found in 100% of primary KS and 75% of KS cell lines, we established an experimental model to test whether BKV may be involved in the pathogenesis of KS. For this purpose, we transformed primary and spontaneously immortalized murine endothelial cells with BKV or with a plasmid containing BKV early region, which encodes BKV T antigen. Murine endothelial cells lost endothelial markers after transformation by BKV and, when inoculated s.c. in nude mice, induced tumors which regressed 7-30 days after onset, whereas spontaneously immortalized murine endothelial MHE cells induced progressing tumors, which brought the animals to death. Histologic examination showed an initial formation of vessels around the tumors, followed by the appearance of a dense population of fibroblasts and mononuclear cells in the peritumoral tissue. Subsequently, tumors appeared to be infiltrated by mononuclear cells and surrounded by a thick fibrous wall with scattered fibroblasts and without vessels. Areas of necrosis developed in the tumor mass and finally the neoplastic tissue completely degenerated. The medium conditioned by BKV-transformed cells induced proliferation and migration of human fibroblasts and NIH3T3 cells. These effects were inhibited by an anti-transforming growth factor-beta1 (TGF-beta1) antibody. Northern blot analysis revealed that BKV-transformed cells express a greater amount of TGF-beta1 RNA than normal murine endothelial cells. Besides, TGF-beta1 was not expressed in progressing tumors induced by spontaneously immortalized endothelial MHE cells, whereas it was highly expressed during the regression of tumors induced by BKV-transformed MHE and primary endothelial cells. Over-expression of TGF-beta1 may be responsible for the mononuclear cell infiltration, inhibition of angiogenesis and formation of the fibrotic wall around tumors, inducing tumor regression through tumor cell necrosis and nutritional starvation. These results prompt us to test whether production of TGF-beta1 is associated with spontaneous KS regression in human patients. In this case, KS regression could be induced or accelerated by any means that enhances TGF-beta1 production at the tumor site.
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PMID:Tumor-host interaction mediates the regression of BK virus-induced vascular tumors in mice: involvement of transforming growth factor-beta1. 1284 79

Primary Effusion Lymphoma (PEL) is a rare and aggressive B-lymphoma caused by Kaposi's sarcoma-associated herpes virus (KSHV) infection that occurs in immunocompromised patients. PEL patients have a poor prognosis. KSHV modulates various cellular signaling pathways to maintain latent infection, and causes malignant conversion of host cells. We previously reported that capsaicin suppressed extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling and induced apoptosis in PEL. Generally, cellular stress such as nutrient starvation, oxidation and virus infection induce CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) expression by activating transcription factor 4 (ATF4), however endoplasmic reticulum (ER) stress induces CHOP expression by both ATF4 and ATF6. CHOP is associated with apoptosis induction and upregulates growth arrest and DNA damage-inducible protein 34 (GADD34) and p53 up-regulated modulator of apoptosis (PUMA) mRNA expression. In this study, we found a new mechanism in which capsaicin induces apoptosis via ATF4-CHOP-PUMA. Capsaicin promoted transcriptional activation of CHOP, which increased mRNA expression of GADD34 and PUMA, resulting in PEL apoptosis. Furthermore, capsaicin increased ATF4 protein levels by promoting ATF4 translation, not transcription, and had no effect on ATF6-dependent transcriptional activation. In sum, capsaicin promotes ATF4 translation and transcriptional induction of CHOP, which results in PUMA expression and apoptosis in PEL cells.
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PMID:Capsaicin Induces ATF4 Translation with Upregulation of CHOP, GADD34 and PUMA. 3136 79