Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral candidiasis (OC) is a frequent oral manifestation of HIV infection, is a marker disease and occurs as a pseudomembranous, erythematous or rarely hyperplastic variant; angular cheilitis is also seen. Candida albicans is frequently isolated but other species such as C. krusei and C. dublienensis are emerging. Resistance against fluconazole is common. Bacterial oral infections are comparatively rare and are predominantly localized to the gingiva and periodontium. Linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis have been described in HIV-infected patients. Initially, these diseases were considered specific for HIV infection. In recent years, however, it has become apparent that gingivitis and periodontitis in HIV-infected patients do not differ from those in immunocompetent individuals. AIDS-associated Kaposi's sarcoma (KS) predominantly occurs at the palate, the gingiva and the dorsum of the tongue. Histopathologically, oral KS is identical to classical KS. Oral KS has been treated surgically, using laser, radiotherapy and intralesional injections with chemo- and immunotherapy. After introduction of highly active antiretroviral therapy (HAART) oral manifestations, such as OC, gingivo-periodontitis and KS are rarely seen.
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PMID:Oral manifestations in HIV infection: fungal and bacterial infections, Kaposi's sarcoma. 1268 60

AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents, we have discovered that AIDS-KS cells express high-affinity receptors for interleukin-4 (IL-4), a pleiotropic immune regulatory cytokine. Molecular studies have revealed that AIDS-KS cells express type II IL-4 receptors, in which IL-4 forms a productive complex with primary IL-4 binding protein (IL-4R beta, also known as IL-4R alpha) and a shared subunit between IL-4 and IL-13R systems (IL-13R alpha', also known as IL-13R alpha 1). A recombinant fusion protein composed of IL-4 and a mutated form of a powerful bacterial toxin called Pseudomonas exotoxin (PE)--the fusion protein is termed IL4(3837)-PE38KDEL or cpIL4-PE--was found to be highly and specifically cytotoxic to AIDS-KS cells in vitro. Normal human immune cells (e.g., resting T and B cells and monocytes) or endothelial cells, a possible precursor of AIDS-KS, expressed low numbers of IL-4R and showed little or no sensitivity to cpIL4-PE. Administration of cpIL4-PE in nude mice with established subcutaneously growing AIDS-KS tumors produced remarkable antitumor activity in a dose-dependent manner with the highest dose exhibiting complete responses without any visible toxicity. KS tumors produced metabolic changes including cachexia, hypoglycemia and lymphopenia, all of which were prevented by cpIL4-PE treatment. These studies indicate that cpIL4-PE is a promising experimental therapeutic agent for treatment of AIDS-KS.
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PMID:IL-4 receptor-directed cytotoxin for therapy of AIDS-associated KS tumors. 1293 11

Infection with HIV-1 is known to impair B cell function. To further elucidate the role of B cells during infection and tumorigenesis, we studied their numbers in cases of AIDS-related Kaposi's sarcoma (KS) during the HAART era. Patients with AIDS-related KS were identified from a database of 4,480 HIV-1 positive individuals and the incidence of KS and rate ratio was stratified according to nadir number of B cells, measured as the CD19 count. In an unadjusted model, we observed that lower B cell counts were associated with a statistically significant increased risk of KS development (p < 0.001). We also observed a trend toward increased counts during KS resolution. When adjusted for nadir CD4 count in a multi-variable model, higher B cell counts were protective against KS development (p = 0.015). These data highlight a potential role for B cells and therefore the humoral immune system in KS aetiopathogenesis.
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PMID:Nadir B cell counts are significantly correlated with the risk of Kaposi's sarcoma. 1464 16

Kaposi's sarcoma is currently the most common tumor in Zimbabwe. The purpose of our study is to compare the effectiveness of supportive care vs. 3 intervention approaches, namely oral Etoposide, a 3-drug combination, and radiotherapy using quality of life (QOL) as the primary measure of success. In addition, our study was to determine whether a disease-specific module has greater sensitivity to group differences than a generic QOL questionnaire and to determine the most pragmatic approach to treating epidemic Kaposi's sarcoma (EKS) in Zimbabwe. Histologically confirmed HIV-positive patients with Kaposi's sarcoma were randomized to receive supportive care only or supportive care plus either radiotherapy, oral Etoposide or a 3-drug combination consisting of actinomycin-D, vincristine and bleomycin. No patient received antiretroviral therapy. The primary outcome was QOL measured by the functional living index-cancer (FLI-C) and supplemented by the Kaposi's sarcoma module (KSM). From 1994-1999, 495 EKS patients were accrued, and 470 were evaluable. Of these, 433 are known to be dead, 26 are lost to follow-up and 11 are still alive. The group treated with oral Etoposide had a significantly better QOL than the radiotherapy group for the total FLI-C score (adjusted mean plus standard error at 3-months 89 +/- 3 vs. 76 +/- 3; p = 0.004) and for the hardship (11 +/- 0.4 vs. 9 +/- 0.4; p = 0.001); social (10 +/- 0.4 vs. 8 +/- 0.4; p = 0.001) and nausea (9 +/- 0.4 vs. 8 +/- 0.4; p = 0.002) subscales. In addition, on the physical and psychological subscales, the Etoposide group had a significantly better QOL than the other 3 treatment groups (p < 0.04). The 3-drug combination, supportive care and radiotherapy groups did not differ significantly from each other with respect to the total FLI-C score or its subscales. There were no group differences with respect to survival. Oral Etoposide therapy resulted in better total FLI-C QOL score than radiotherapy. As well, Etoposide resulted in better physical and psychological subscale scores than radiotherapy, 3-drugs and supportive care. Thus, funds permitting, oral Etoposide is a pragmatic approach to treating EKS in an environment where antiretroviral drugs are not universally available. The study underscores the value of undertaking studies in areas of disease prevalence and the necessity of selecting appropriate outcome measures.
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PMID:Treatment of AIDS-associated Kaposi's sarcoma in Zimbabwe: results of a randomized quality of life focused clinical trial. 1547 10

Comprehensive data describing epidemiological characteristics of the human herpesvirus-8 or Kaposi's sarcoma-associated herpesvirus (HHV-8 or KSHV) infection among pregnant women in a central sub-Saharan Africa are not available. This study determined virus prevalence estimates and the risk factors associated with HHV-8 infection. Cross-sectional, enrollment visit data were analyzed from a prospective cohort study of perinatal transmission of HHV-8 in Lusaka, Zambia. Exposure data were obtained via structured interview, physical examination, medical chart review, and laboratory testing. Among 3,160 antenatal women serologically screened for HHV-8 between September 1998 and October 2000, 40.2% were seropositive. The HHV-8 positive women were more likely to be co-infected with HIV-1 than those who were HHV-8 negative (34% vs. 26%; P < 0.0001). Of 154 variables evaluated by logistic regression analyses, only three risk factors, have emerged as independent predictors of HHV-8 positive serology: diagnosis of genital warts, HIV-1 co-infection and primary education. The association of HHV-8 infection with genital warts and HIV-1 co-infection suggests heterosexual transmission of HHV-8. HIV-1 infection may also act as a marker for particular behaviors, which could be sexual in nature, that are associated with both HIV-1 and HHV-8 transmission. Since HHV-8 facilitates development of AIDS-related Kaposi's sarcoma (KS), the results of this study could be utilized to identify specific population groups of pregnant women who are at increased risk for this disease.
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PMID:Epidemiological characteristics of human herpesvirus-8 infection in a large population of antenatal women in Zambia. 1554 82

The introduction of highly active antiretroviral therapy (HAART) has changed the natural history of AIDS-associated Kaposi's sarcoma (KS). Although the use of HAART remains limited in low-resource settings, there are global initiatives to make these drugs available to several millions of HIV-infected persons. While there are multiple reports of KS regression during HAART with or without chemotherapy, there is little documentation on KS management in resource-limited settings. In this paper we review current KS treatments available worldwide and discuss the implications of the increased access to antiretrovirals for KS treatment strategies in resource-limited settings.
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PMID:Management of Kaposi's sarcoma in resource-limited settings in the era of HAART. 1587 57

The aggressive and malignant nature of AIDS-associated Kaposi's sarcoma (KS) lesions have largely been ascribed to Tat, the HIV-1 transactivator protein. Among other activities, HIV-Tat induces the migration and invasion of KS and endothelial cells. Since cell invasion is strictly correlated to the activity of lytic enzymes, we elucidated the role of the cell-associated plasminogen activation system in Tat-dependent and in constitutive invasion and proliferation of KS and of microvascular endothelial cells (MVEC). We demonstrate that KS cells and MVEC express the u-PA receptor (u-PAR) and release plasminogen activators and plasminogen activator inhibitor type-1 (PAI-1). The urokinase-type plasminogen activator (u-PA) is chemotactic, chemoinvasive and mitogenic for KS cells and for MVEC. Conditioned medium from KS cells induced invasion and proliferation of MVEC through the u-PA/u-PAR system. Tat is motogenic and mitogenic on KS cells and MVEC, and stimulates morphogenesis of MVEC. These activities were inhibited following antagonization of u-PA and u-PAR, which also reduced constitutive proliferation and invasion of KS cells and MVEC. These data indicate that the u-PA/u-PAR/PAI-1 system is involved in KS-induced endothelial cell invasion, proliferation, and differentiation. Further, exogenous Tat protein could up-regulate the fibrinolytic system, increasing its influence on KS and endothelial cell proliferation and migration, potentially promoting KS progression. These observations suggest the potential for application of u-PA/u-PAR system inhibitors for control of AIDS-associated KS, that has a high risk of recurrence with highly active antiretroviral therapy failure, and of other KS forms.
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PMID:The urokinase-type plasminogen activator, its receptor and u-PA inhibitor type-1 affect in vitro growth and invasion of Kaposi's sarcoma and capillary endothelial cells: role of HIV-Tat protein. 1594 64

AIDS-related Kaposi's sarcoma (KS) is a neoplasm that results from the co-infection of HIV and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8). Targeting HIV with highly active antiretroviral therapy has attenuated the natural history of this disease. Recent discoveries have elucidated the role of multiple signaling pathways in the pathogenesis of AIDS-related KS. In particular, KSHV/HHV8-specific gene products, including a G-protein-coupled receptor (vGPCR) and a homolog of human IL-6 (vIL-6), have been implicated in the development of tumorigenesis and angiogenesis. In addition, KSHV/HHV8 can modulate cellular growth and angiogenic pathways to augment malignant transformation and potentiate growth. This article discusses the main signaling pathways that are implicated in the pathogenesis of AIDS-related KS, reviews recently completed clinical trials and anticipates the future direction of molecularly targeted agents in this disease.
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PMID:Investigational agents for treatment of AIDS-related Kaposi's sarcoma. 1737 Nov 97

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

Kaposi's sarcoma is a vascular tumor of skin and viscera first described in 1872. Prior to the 1980s, this disease was rarely seen in the Western world, but was quite prevalent in Sub-Saharan African countries. Since the onset of the HIV pandemic in the 1980s, the incidence of Kaposi's sarcoma has increased markedly in Africa and continues to be a significant problem in association with AIDS in Western countries. Many therapies have been demonstrated to be effective in the treatment of HIV-related Kaposi's sarcoma, including alitretinoin gel, interferon alpha, and various forms of cytotoxic chemotherapy. Antiretroviral therapy combined with cytotoxic agents has yielded significantly greater efficacy than chemotherapy alone. However, as reviewed in this report, pegylated liposomal doxorubicin has been established as the treatment of choice for patients with AIDS-associated Kaposi's sarcoma in Western countries. Compelling preclinical and clinical evidence, reviewed herein, has demonstrated that the nanoparticle (pegylated liposome) delivery system of this formulation leads to greater tumor localization of doxorubicin and consequent improved efficacy, as well as reduced toxicity.
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PMID:Pegylated liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma. 1801 33


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