Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among patients with congenital and acquired immunodeficiencies, non-Hodgkin's lymphoma (NHLs ) are the most common tumors of the immune system. In the setting of human immunodeficiency virus (HIV) infection, as many as 10% to 20% of people ultimately developed NHLs. These tumors are clinically aggressive, frequently involve extranodal sites, and often exhibit unique features that distinguish them from NHL arising in individuals with other forms of immunosuppression. Important in the development of HIV-associated NHL are cytokines and other factors that induce B-cell proliferation and increase the likelihood of mutations of c-myc, bcl-6, and other tumor-suppressor genes with carcinogenic potential. Specific forms of HIV-associated NHL are linked to expression of Epstein-Barr virus (EBV)-latent proteins; the newly described DNA virus, Karposi's sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV-8); and perhaps HIV. Elucidation of the factors that contribute to the high incidence of NHL among patients infected with HIV provides insights into important elements of lymphomagenesis.
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PMID:Epidemiology and pathogenesis of AIDS-related lymphomas. 968 78

Kaposi's sarcoma (KS) is an angioproliferative disease occurring in 4 clinic-epidemiologic forms. Although the AIDS-associated KS (AIDS-KS) is the most aggressive, all forms of KS share the same immunological and histopathological features suggesting common etiological and pathogenic factors. Recent data indicate that at least in early stage KS is not a real sarcoma but an angiohyperplastic-inflammatory lesion mediated by inflammatory cytokines and angiogenic factors, that is triggered or amplified by infection with human herpesvirus-8. In addition, the human immunodeficiency virus type-1 Tat protein appears to be responsible for the higher grade of aggressiveness of AIDS-KS as compared to the other forms of KS. However, given time, reactive KS may progress to a sarcoma as suggested by evidence of monoclonality in late-nodular lesions.
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PMID:Kaposi's sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents. 972 Jul 57

A seroprevalence study of bovine lentivirus, known as bovine immunodeficiency virus (BIV), was conducted in 12 different dairy herds in Hokkaido, where some herds were a high prevalence of bovine leukemia virus (BLV) infection. Amongst 611 cattle, 28.6% of cattle were BLV-seropositive, and 11.7% of cattle were seropositive for BIV, while 4.2% of cattle were seropositive for both BIV and BLV. For the isolation of BIV, 19 samples of peripheral blood mononuclear cells (PBMC) and one sample of milk-derived leukocytes were prepared from BIV-seropositive cows. These PBMC and leukocyte preparations were then co-cultivated with cc81 cells, a cat cell line transformed by mouse sarcoma virus. BIV was isolated from 17 PBMC and one milk-derived leukocyte samples. The isolated viruses showed slow replication and syncytia formation. Major core antigen, p26 from these isolates were reacted with anti-BIV (American isolate R-29) serum. In addition, proviral DNA was detected in blood and milk samples by nested polymerase chain reaction and subsequent Southern blot hybridization. Nucleotide sequence analysis of the amplified pol gene products showed its 99.0 to 99.7% homology to that of BIV R-29. These results indicate that the Japanese BIV isolates appear to be antigenically and genetically similar to the American R-29. Since BIV was isolated from milk samples, BIV could possibly be transmitted through milk. This is the first report of BIV isolation in Japan.
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PMID:Seroprevalence and field isolation of bovine immunodeficiency virus. 985 99

The fluoroquinolone derivatives have been shown to inhibit human immunodeficiency virus (HIV) replication at the transcriptional level. We confirmed the anti-HIV activity of the most potent congener, 8-difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2- methoxyphenyl)-1-piperazinyl]-4-quinolone-3-carboxylic acid (K-12), in both acutely and chronically infected cells. K-12 was active against different strains of HIV-1 (including AZT- and ritonavir-resistant HIV-1 strains), HIV-2 and simian immunodeficiency virus, in MT-4, CEM, C8166 and peripheral blood mononuclear cells. In all of these antiviral assay systems, K-12 showed a similar activity (EC50 0.2-0.6 microM). K-12 inhibited Moloney murine sarcoma virus-induced transformation of C3H/3T3 cells with an EC50 of 6.9 microM. Also, K-12 proved inhibitory to herpesvirus saimiri, human cytomegalovirus, varicella-zoster virus and herpes simplex virus types 1 and 2 (in order of decreasing sensitivity), but was not inhibitory (at subtoxic concentrations) to human herpesvirus type 8 (as evaluated in BCBL-1 cells), vaccinia virus, Sindbis virus, vesicular stomatitis virus, respiratory syncytial virus, Coxsackie virus, Punta Toro virus, parainfluenza virus or reovirus. Time-of-addition experiments and quantitative transactivation bioassays indicated that K-12 inhibits the Tat-mediated transactivation process in HIV-infected cells.
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PMID:Broad-spectrum antiviral activity and mechanism of antiviral action of the fluoroquinolone derivative K-12. 987 93

The retroviral protease (PR) is absolutely essential for completion of human immunodeficiency virus multiplication cycle, and cannot be replaced by any cellular function. Thus PR, like reverse transcriptase, is an ideal target for the development of anti-AIDS therapy. A large number of human immunodeficiency virus type-1 (HIV-1) PR inhibitors have been developed, and several are currently used as anti-AIDS drugs. These inhibitors are mainly based on the natural PR cleavage sites within the viral Gag and Gag-Pol precursors. The major difficulty encountered while using anti-HIV therapeutic agents in patients has been the rapid emergence of drug-resistant viral strains. Most of the mutations which convert the PR into inhibitor-resistant are located within the substrate binding subsites of the enzyme. Recently, it has been shown that the HIV-1 auxiliary protein Vif, and especially the N-terminal half of Vif (N'-Vif) specifically interacts with the viral PR and inhibits its activity. We now show that efficient inhibition of HIV-1 PR activity can be achieved using Vif-derived peptides. Based on the above model we have performed peptide mapping of N'-Vif in order to find a small peptidic lead compound which inhibits PR activity. The screening revealed that peptides derived from two regions in Vif spanning from residues 30-65 and 78-98 inhibit PR activity in vitro, specifically bind HIV-PR and inhibit HIV-1 production in vivo. Further mapping of these regions revealed the lead compounds Vif81-88 and Vif88-98. These peptides specifically inhibit and bind HIV-1 PR, but do not affect pepsin and rous sarcoma virus protease. In contrast to other known PR inhibitors, these peptides are not substrate-based and their sequences do not resemble the sequences of the natural PR substrates (cleavage sites). Moreover, the Vif-derived peptides themselves are not cleaved by HIV-1 PR. Conversion of the lead peptides into small backbone cyclic peptidomimetics is taking place nowadays in order to turn these lead compounds into metabolically stable selective novel type of HIV-PR non-substrate-based inhibitors.
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PMID:Peptides derived from HIV-1 Vif: a non-substrate based novel type of HIV-1 protease inhibitors. 1007 9

Kaposi's sarcoma (KS) is a form of skin cancer, most commonly found in individuals suffering from acquired immunodeficiency syndrome, or AIDS. However, before the worldwide infection of human immunodeficiency virus (HIV), the rare occurrence of KS was confined to two distinct groups of individuals. In the Western world, the classical form of KS was often found in older men (60-70 years of age) from the Mediterranean area. Another form called endemic KS, was found in Equatorial Africa. Currently, the most common cases of KS are found in individuals suffering from AIDS. This is called AIDS-associated KS. Between 30 and 40% of male, homosexual AIDS patients suffer from AIDS-associated KS. KS is also occasionally diagnosed in transplant patients receiving immunosuppressive drugs (to keep their body from rejecting the foreign organ). As opposed to cases of classic and endemic KS, the KS in AIDS patients progresses very quickly, often with a fatal outcome. Human herpesvirus type 8 (HHV-8) has been implicated as the cause of Kaposi's sarcoma (KS), but the exact connection of the virus to the neoplasm is not known. The virus has been detected within the sarcoma skin lesions, but has additionally been seen in peripheral blood cells, semen samples, prostate tissue, and other types of soft tissue tumors. In this study, we evaluated HHV-8 within the skin lesion of KS as well as in semen specimens obtained from HIV-1 infected and uninfected specimens from HIV-1-seronegative individuals. Twenty-eight tissue samples representing AIDS-associated, endemic KS, and six non-KS patients were collected for observation from different centers throughout the world. The tissues were examined utilizing in situ polymerase chain reaction (ISPCR) and hybridization to identify and localize the herpesvirus within the KS lesions. With the use of the sensitive ISPCR technique, HHV-8 DNA was detected in the spindle cells within the nodular skin lesions, as well as in the microvascular endothelial cells which line small vessels within the lesions in all forms of KS. In addition, we analysed semen specimens from HIV-1 infected and uninfected men, our analyses revealed that HHV-8 was present in the significant proportions of the HIV-1-infected-individuals' sperm, as well as in the mononuclear cells of the semen specimens. HHV-8 DNA was demonstrated, by ISPCR, in KS lesions as well as in seminal mononuclear cells and sperm of significantly high proportion of HIV-1-infected men. What role the presence of HHV-8 in the sperm cells plays in the sexual transmission of this herpesvirus will require further study. However, the reports which demonstrate that KS lesions can develop in infants of only a few weeks of age, increases the possibility that this agent may be vertically transmitted. It can be suggested that HHV-8 is relatively ubiquitous and its frequency increases with the increasing immunosuppression.
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PMID:Localization of human herpesvirus type 8 (HHV-8) in the Kaposi's sarcoma tissues and the semen specimens of HIV-1 infected and uninfected individuals by utilizing in situ polymerase chain reaction. 1021 7

We constructed human immunodeficiency virus type 1 (HIV-1) vectors that will allow higher levels of gene expression in T cells. Gene expression under the control of an internal cytomegalovirus (CMV) immediate-early promoter in a self-inactivating lentiviral vector (CSCG) is 4- to 15-fold lower in T-cell lines (SUPT1 and CEMX174) than in non-lymphoid-cell lines (HeLa and 293T). This is in contrast to a Moloney murine leukemia virus (MoMLV)-based retrovirus vector (SRalphaLEGFP). We therefore replaced the internal CMV promoter of CSCG with three different murine oncoretroviral long terminal repeat (LTR) promoters-murine sarcoma virus (MSV), MoMLV (MLV), and the LTR (termed Rh-MLV) that is derived from the ampho-mink cell focus-forming (AMP/MCF) retrovirus in the serum of one rhesus macaque monkey that developed T-cell lymphoma following autologous transplantation of enriched bone marrow stem cells transduced with a retrovirus vector preparation containing replication-competent viruses (E. F. Vanin, M. Kaloss, C. Broscius, and A. W. Nienhuis, J. Virol. 68:4241-4250, 1994). We found that the combination of Rh-MLV LTR and a partial gag sequence of MoMLV (Deltagag(871-1612)) in CS-Rh-MLV-E gave the highest level of enhanced green fluorescent protein (EGFP) gene expression compared with MLV, MSV LTR, phosphoglycerate kinase, and CMV promoters in T-cell lines, as well as activated primary T cells. Interestingly, there was a further two- to threefold increase in EGFP expression (thus, 10-fold-higher expression than with CMV) when the Rh-MLV promoter and Deltagag(871-1612) were used in a self-inactivating-vector setting that has a further deletion in the U3 region of the HIV-1 LTR. These hybrid vectors should prove useful in gene therapy applications for T cells.
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PMID:A murine leukemia virus (MuLV) long terminal repeat derived from rhesus macaques in the context of a lentivirus vector and MuLV gag sequence results in high-level gene expression in human T lymphocytes. 1072 43

Chronic infection with hepatitis B virus (HBV) in humans is strongly linked to the development of hepatocellular carcinoma (HCC). Activation of growth-regulatory genes may play a crucial role in carcinogenesis. Proto-oncogene expression has been shown to be higher in HCC tissue with integrated HBV DNA than in the normal liver. Earlier, we showed that the 3' end of the HBV major surface gene (S) (426-855 nucleotides of the S region) is a transactivator of the X promoter-enhancer regulatory element in co-transfection experiments. This region expresses a truncated carboxy terminal S protein extending from amino acid residues 102 to 226. In this study, the truncated S protein (trc-S) was examined for its enhancing activity on several viral and cellular regulatory elements. The results indicate that trc-S activates rous sarcoma virus long terminal repeat (LTR), human T-lymphotropic virus 2 LTR, human immunodeficiency virus 1 LTR, and the c-jun and c-fos promoters. Electrophoretic mobility shift assays carried out to investigate its DNA-binding properties established that trc-S binds to HBV X promoter and oligonucleotides representing binding sites for the AP1 and TFIID transcription factors. The specificity of this interaction was confirmed by using competition experiments and supershift assays. These experiments suggest that trc-S is a transactivator of several cellular and viral promoters and that this activity is mediated by direct interaction with DNA.
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PMID:Hepatitis B virus surface (S) transactivator with DNA-binding properties. 1074 25

The human herpes virus 8 (HHV8) or Kaposi's sarcoma-associated herpes virus (KSHV) is present in all Kaposi's sarcoma, and the detection of the virus using polymerase chain reaction or in situ hybridization is a highly sensitive and specific diagnostic test for the diagnosis of this neoplasm. HHV8 is furthermore invariably present in primary effusion lymphoma (PEL) and has also been detected in patients with acquired immunodeficiency syndrome (AIDS)-associated multicentric Castleman's disease (MCD) as well as, to a lesser extent, in non-AIDS MCD. In contrast to Kaposi's sarcoma, in which the tumor cells show primarily latent HHV8 infection, a higher rate of lytically infected cells can be observed in MCD. Epidemiological surveys indicate that the seroprevalence for HHV8 parallels the risk of developing Kaposi's sarcoma--5-10% in the general population of the Western world but ranging up to 20-70% in homosexual human immunodeficiency virus (HIV)-infected patients, and the infection precedes the development of Kaposis's sarcoma. Finally, HHV8 has been reported in a number of other diseases, especially in multiple myeloma. However, the highly controversial role of HHV8 in these lesions has to be clarified. Based on the data available today, HHV8 can be assigned as a new human virus, associated with tumors.
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PMID:Human herpes virus 8: a new virus discloses its face. 1078 77

Kaposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus-8 (HHV-8), is a recently described gamma-herpes virus that has been etiologically linked to two different acquired immunodeficiency syndrome (AIDS)-related malignancies by strong epidemiologic and pathologic evidence. Infection been shown to precede and predict the development of Kapasi's sarcoma (KS) in human immunodeficiency virus (HIV)-infected patients, and viral DNA has been found in KS lesions of all types and stages. Furthermore, KSHV is a lymphotropic virus and is present in nearly all cases of primary effusion lymphoma, a rare malignancy disproportionately affecting HIV-infected individuals. KSHV is also thought to dramatically affect the incidence, type, and course of multicentric Castleman's disease, another lymphoproliferative disorder over-represented in people with AIDS. KSHV encodes many potentially oncogenic products, including several apparently pirated from the human genome. These include various chemokines, cell cycle regulatory proteins, and survival and proliferation factors. Knowledge is rapidly accumulating concerning the viral pathogenic mechanisms and host cofactors necessary for KSHV-mediated disease.
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PMID:Kaposi's sarcoma-associated herpes virus and acquired immunodeficiency syndrome-related malignancy. 1095 Mar 67


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