Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly active anti-retroviral treatment (HAART) is currently the most effective treatment for HIV/AIDS. Additionally, HIV positive patients receiving HAART have a better health-related quality of life (HRQoL). Cancers previously associated with HIV/AIDS also known as the AIDS defining cancers (ADCs), such as Kaposi's sarcoma and non-Hodgkin's lymphoma have been on the decline since the introduction of HAART. However, non-AIDS defining cancers (NADCs), in particular, lung cancers have been documented to be on the rise. The association between the use of HAART components and lung carcinogenesis is poorly understood. This study aimed at elucidating the effects of two HAART components [efavirenz (EFV), and lopinavir/ritonavir (LPV/r)] on lung cancer. This was achieved through the use of in vitro cell biological approaches to assess cell health, including cell viability, Real Time Cell Analysis (RTCA) growth monitoring, evaluation of the cell cycle, and progression to apoptosis, following on drug treatments. At plasma level concentrations, both EFV and LPV/r induced S-phase arrest, while at lower concentrations both drugs promoted the progression of cells into G2/M phase following cell cycle FACS analysis. At higher concentrations although cell viability assays reflected anti-proliferative effects of the drugs, this was not statistically significant. RTCA showed a significant decline in cell viability in response to the highest dose of LPV/r. Dual staining by Annexin V-FITC and PI confirmed significant pro-apoptotic effects were promoted by LPV/r. Both EFV and LPV/r exert double-edged oncogenic effects on MRC-5 and A549 lung cells, acting to either promote cell proliferation or to enhance apoptosis. This is affected by EFV and LPV/r altering cell cycle progression, with a significant S-phase arrest, this being an indication of cellular stress, cytotoxicity, and DNA damage within the cell.
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PMID:Efavirenz and Lopinavir/Ritonavir Alter Cell Cycle Regulation in Lung Cancer. 3298 47

Inflammation triggered by innate immunity promotes carcinogenesis in cancer. Kaposi's sarcoma (KS), a hyperproliferative and inflammatory tumor caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection, is the most common cancer in AIDS patients. KSHV infection sensitizes cells to pathogen-associated molecular patterns (PAMPs). We examined the role of Pseudomonas aeruginosa, an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. P. aeruginosa stimulation increased cell proliferation and efficiency of colony formation in soft agar of KSHV-transformed rat primary mesenchymal precursor (KMM) cells but had no significant effect on the untransformed (MM) cells. P. aeruginosa stimulation also increased cell proliferation of KSHV-infected human B cells, BJAB, but not the uninfected cells. Mechanistically, P. aeruginosa stimulation resulted in increased inflammatory cytokines and activation of p38, ERK1/2, and JNK mitogen-activated protein kinase (MAPK) pathways in KMM cells while having no obvious effect on MM cells. P. aeruginosa induction of inflammation and MAPKs was observed with and without inhibition of the Toll-like receptor 4 (TLR4) pathway, while a flagellin-deleted mutant of P. aeruginosa required a functional TLR4 pathway to induce inflammation and MAPKs. Furthermore, treatment with either lipopolysaccharide (LPS) or flagellin alone was sufficient to induce inflammatory cytokines, activate MAPKs, and increase cell proliferation and efficiency of colony formation in soft agar of KMM cells. These results demonstrate that both LPS and flagellin are PAMPs that contribute to P. aeruginosa induction of inflammation in KSHV-transformed cells. Because AIDS-KS patients are susceptible to P. aeruginosa infection, our work highlights the preventive and therapeutic potential of targeting P. aeruginosa infection in these patients.IMPORTANCE Kaposi's sarcoma (KS), caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV), is one of the most common cancers in AIDS patients. KS is a highly inflammatory tumor, but how KSHV infection induces inflammation remains unclear. We have previously shown that KSHV infection upregulates Toll-like receptor 4 (TLR4), sensitizing cells to lipopolysaccharide (LPS) and Escherichia coli In the current study, we examined the role of Pseudomonas aeruginosa, an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. P. aeruginosa stimulation increased cell proliferation, inflammatory cytokines, and activation of growth and survival pathways in KSHV-transformed cells through two pathogen-associated molecular patterns, LPS and flagellin. Because AIDS-KS patients are susceptible to P. aeruginosa infection, our work highlights the preventive and therapeutic potential of targeting P. aeruginosa infection in these patients.
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PMID:Pseudomonas aeruginosa Stimulates Inflammation and Enhances Kaposi's Sarcoma Herpesvirus-Induced Cell Proliferation and Cellular Transformation through both Lipopolysaccharide and Flagellin. 3317 8


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