Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-interferon (IFN)-alpha antibodies were determined in the serum of 28 patients treated with high-dose human recombinant IFN-alpha-2a for AIDS-associated Kaposi's sarcoma. After a median treatment duration of 3 months, 3 patients developed anti-IFN-alpha antibodies, of whom 2 showed a long lasting tumour response despite the development of these antibodies. None of 3 patients with tumour progression after an initial treatment response had developed IFN-alpha neutralizing antibodies. In conclusion, a low incidence of anti-IFN-alpha antibodies during treatment with high dose IFN-alpha was found, but the appearance had no detrimental effect on the duration of tumour responses in a small number of patients.
Int J STD AIDS 1990 Jul
PMID:Low incidence of anti-interferon-alpha antibodies in patients treated with interferon-alpha-2a for AIDS-associated Kaposi's sarcoma. 208 34

AIDS-associated Kaposi's sarcoma (KS) is much more frequent in patients acquiring HIV infection via the sexual route. Epidemiological studies have confirmed the likely involvement of a sexually acquired cofactor in the pathogenesis of this form of KS. We have formulated a set of postulates, epidemiological and experimental, to fit a single unifying hypothetical agent. Chlamydia trachomatis is one of 3 agents to fit the epidemiological criteria. Our data suggest a possible association between increased IgG serum antibody to C. trachomatis and the occurrence of KS. Conversely, higher titres of IgG serum antibody to C. pneumoniae were associated with the absence of KS. We feel that it is important to study further the relationship between C. trachomatis and KS.
Int J STD AIDS
PMID:Chlamydia trachomatis as a possible cofactor for Kaposi's sarcoma in AIDS. 884

A phase II study of thalidomide was conducted to evaluate its efficacy and toxicity in the treatment of cutaneous AIDS-related Kaposi's sarcoma (AIDS-KS). To evaluate whether clinical response is correlated with titre of human herpesvirus 8 (HHV8) DNA in peripheral blood, levels were determined by serial end-point dilution at enrolment and 4-6 weeks later. Seventeen male HIV-seropositive patients with histopathologically diagnosed KS were treated with thalidomide 100mg orally once nightly for 8 weeks. Response evaluation was performed using AIDS Clinical Trials Group (ACTG) criteria and analysis was by intention to treat. Six of 17 patients achieved a partial response (35%: 95% confidence interval 10-61%). Eight patients withdrew (6 owing to toxicity, one to early progression and one to non-compliance). HHV8 DNA load decreased by at least 3log10 to undetectable levels in 3 of the 5 virologically assessable partial responders. This preliminary study demonstrates that thalidomide has activity in the treatment of AIDS-KS and that clinical response is associated with a reduction of HHV8 DNA titre in peripheral blood.
Int J STD AIDS 1998 Dec
PMID:Activity of thalidomide in AIDS-related Kaposi's sarcoma and correlation with HHV8 titre. 987 23

The efficacy and toxicity of interferon-alpha2a (9MU/d) and bleomycin (15 mg every 2 weeks), each combined with zidovudine (2x250 mg/d), was compared in a randomized study in 26 men with progressing AIDS-related Kaposi's sarcoma (KS). The median CD4 count was 113/microl. Complete or partial response was achieved in one (8%) of 12 evaluable patients on interferon and in 2 (20%) of 10 patients on bleomycin (P = 0.43) during 4.7 and 5.3 months of treatment, respectively. The tolerability was comparable. During extended follow up, survival time was 24 and 13 months in the interferon and bleomycin arm, respectively. In a multivariate Cox regression analysis, CD4 lymphocytes <200/microl (relative risk 3.74; 95% CI: 1.30-10.8) and randomization to interferon (relative risk 0.37; 95% CI: 0.15-0.90) were significantly predictive of mortality. New AIDS-related events occurred more frequently in patients who had received bleomycin. The antiviral activity of interferon-alpha or the chemotherapy-mediated increase in the risk for opportunistic infections may explain these differences.
Int J STD AIDS 1999 Jun
PMID:A randomized trial of interferon-alpha2a and zidovudine versus bleomycin and zidovudine for AIDS-related Kaposi's sarcoma. Swiss HIV Cohort Study. 1041 79

Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released from KS and host cells and HIV viral products-the protein Tat are reported to be involved in angiogenesis. Mounting evidence further suggests that multiple angiogenic activities of Tat contribute to AIDS-associated Kaposi's sarcoma (AIDS-KS). Herein, we report that sulfated polymannuroguluronate (SPMG), a novel anti-AIDS drug candidate now undergoing phase II clinical trial, significantly eliminated Tat-induced angiogenesis in SLK cells both in vitro and in vivo. SPMG significantly and dose-dependently inhibits proliferation, migration, and tube formation by SLK cells. SPMG also dramatically arrested Tat-driven KDR phosphorylation and blocked the interaction between Tat and integrin beta1, thus inhibiting the phosphorylation of the downstream kinases of FAK, paxillin and MAPKs. In addition, SPMG was noted to block the release of bFGF and VEGF from ECM. All these collectively favor an issue that SPMG functions as a promising therapeutic against Tat-induced angiogenesis and pathologic events relevant to AIDS-KS, which adds novel mechanistic profiling to the anti-AIDS action of SPMG.
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PMID:Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits HIV-1 Tat-induced angiogenesis in Kaposi's sarcoma cells. 1786 50

AIDS-related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe the pattern of presentation and survival in Jos, Nigeria. We identified 48 HIV-positive patients with AIDS-KS and matched them for age and sex with an equal number of HIV-positive patients without AIDS-KS. We compared their clinical, immunological, virological characteristics and survival. They were similar in age and body mass index profile but patients with AIDS-KS had more tuberculosis co-infection (P, 0.02), lower median CD4 count (P, 0.003) and higher mortality (P, 0.002). Surprisingly, patients with AIDS-KS had lower levels of median viral load (29,347 copies/mL) compared with controls (80,533 copies/mL). We recommend specific AIDS-KS therapy in addition to highly active antiretroviral therapy in order to improve survival.
Int J STD AIDS 2009 Jun
PMID:Presentation and survival of patients with AIDS-related Kaposi's sarcoma in Jos, Nigeria. 1945 27

Roll-out of combination antiretroviral therapy (cART) in South Africa should impact on AIDS-associated Kaposi's sarcoma (KS). Government provision began in 2003, with 23% coverage for World Health Organization (WHO) stage IV AIDS in 2006. To assess the effect of cART availability on KS management, we evaluated records from 701 KS patients seen at a tertiary oncology centre in KwaZulu-Natal, South Africa, from 1995 to 2006. Associations between cART use and measures of KS care were evaluated. cART availability was 0% prior to 2001, 9.6% (2001-2003) and 44% (2004-2006). Documentation of HIV status increased incrementally from 65% to 92%. cART was associated with chemotherapy administration: 56% on cART versus 17% not on cART (P < 0.001); and less loss to follow-up, 13% on cART versus 38% not on cART (P < 0.001). cART availability improves the care of AIDS-associated KS. Further increases in cART availability for this population are needed in South Africa.
Int J STD AIDS 2011 Nov
PMID:An evaluation of the early effects of a combination antiretroviral therapy programme on the management of AIDS-associated Kaposi's sarcoma in KwaZulu-Natal, South Africa. 2209 54

Conjunctival involvement by AIDS-associated Kaposi's sarcoma (KS) is rare, more so in women. We present a case of a 34-year-old African-American woman with AIDS, who was admitted to our hospital and diagnosed with KS of the conjunctiva. To date there are only a few reported cases of AIDS-associated conjunctival KS in the literature. This case is the first case of AIDS-associated conjunctival KS in an African-American woman and emphasizes the importance of considering KS as a differential diagnosis of the conjunctival mass in HIV-positive patients.
Int J STD AIDS 2012 Mar
PMID:AIDS-associated Kaposi's sarcoma of the conjunctiva in a woman. 2258 81

Epidemic Kaposi's sarcoma remains the most common cancer in patients with human immunodeficiency virus and is associated with significant morbidity and mortality in AIDS patients. Primary visceral Kaposi's sarcoma (Kaposi's sarcoma without cutaneous lesions) presenting with lower gastrointestinal bleeding (LGIB) has rarely been reported. Though Kaposi's sarcoma can occur anywhere in gastrointestinal tract, gastrointestinal symptoms are often non-specific such as chronic blood loss anaemia, vomiting, diarrhoea, intestinal obstruction. In these patients, severe gastrointestinal bleeding requiring repeated blood transfusions is extremely rare. Clinicians should be aware of gastrointestinal tract Kaposi's sarcoma since visceral Kaposi's sarcoma can present in the absence of cutaneous involvement. Endoscopy with biopsy is useful in the diagnosis for severe LGIB in patients with AIDS. Furthermore, gastrointestinal Kaposi's sarcoma should be considered in the differential diagnosis of GI bleeding. We report a case of primary colonic KS who presented with recurrent GI bleeding which was eventually diagnosed by sigmoidoscopy and confirmed pathologically.
Int J STD AIDS 2013 Nov
PMID:Recurrent lower gastrointestinal bleeding due to primary colonic Kaposi's sarcoma in a patient with AIDS. 2397 Jun 16

Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), in addition to an MCD-related disorder involving systemic elevation of proinflammatory cytokines, including vIL-6 and human IL-6 (hIL-6). In these diseases, lytic (productive) replication, in addition to viral latency, is believed to play a critical role. Proreplication activity of vIL-6 has been identified experimentally in PEL and endothelial cells, but the relative contributions of different vIL-6 interactions have not been established. Productive interactions of vIL-6 with the IL-6 signal transducer, gp130, can occur within the ER, but vIL-6 also interacts in the ER with a nonsignaling receptor called vitamin K epoxide reductase complex subunit 1 variant 2 (VKORC1v2), calnexin, and VKORC1v2- and calnexin-associated proteins UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) and glucosidase II (GlucII). Here, we report the systematic characterization of interaction-altered vIL-6 variants and the lytic phenotypes of recombinant viruses expressing selected variants. Our data identify the critical importance of vIL-6 and its ER-localized activity via gp130 to productive replication in inducible SLK (epithelial) cells, absence of detectable involvement of vIL-6 interactions with VKORC1v2, GlucII, or UGGT1, and the insufficiency and lack of direct contributory effects of extracellular signaling by vIL-6 or hIL-6. These findings, obtained through genetics-based approaches, complement and extend previous analyses of vIL-6 activity.IMPORTANCE Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) was the first viral IL-6 homologue to be identified. Experimental and clinical evidence suggests that vIL-6 is important for the onset and/or progression of HHV-8-associated endothelial-cell and B-cell pathologies, including AIDS-associated Kaposi's sarcoma and multicentric Castleman's disease. The protein is unusual in its poor secretion from cells and its intracellular activity; it interacts, directly or indirectly, with a number of proteins beyond the IL-6 signal transducer, gp130, and can mediate activities through these interactions in the endoplasmic reticulum. Here, we report the characterization with respect to protein interactions and signal-transducing activity of a panel of vIL-6 variants and utilization of HHV-8 mutant viruses expressing selected variants in phenotypic analyses. Our findings establish the importance of vIL-6 in HHV-8 productive replication and the contributions of individual vIL-6-protein interactions to HHV-8 lytic biology. This work furthers understanding of the biological significance of vIL-6 and its unique intracellular interactions.
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PMID:Genetic Analyses of Contributions of Viral Interleukin-6 Interactions and Signaling to Human Herpesvirus 8 Productive Replication. 3266 40


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