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

With rapid scientific advances in HIV pathogenesis and antiretroviral therapy, the oncologist is faced with new challenges in the treatment of patients with HIV infection and malignancy. HIV infection, by causing immune dysregulation and cytokine production, may alter the natural history of certain neoplasms. Treatment of cancer with chemotherapy can also affect the course of HIV disease. The use of combination antiretroviral agents, particularly the protease inhibitors, can maximally suppress replication of HIV. Improved clinical outcome is associated with more profound decreases in plasma HIV RNA, although development of resistant strains may hinder sustained antiretroviral activity. Antiretroviral therapy should be continued during chemotherapy with the goal of achieving plasma HIV-RNA levels below 500 copies/mL. Modifications in the regimen should be done when intolerable toxicity occurs or if viral load is increased. Although information regarding the use of newer antiretroviral agents with chemotherapy is limited, the use of several reverse transcriptase inhibitors has been well tolerated in patients with AIDS-related malignancies such as Kaposi's sarcoma and lymphoma.
 ...
PMID:The use of new antiretroviral therapy in combination with chemotherapy. 932 24

Considerable progress has recently been achieved in understanding the pathogenesis of human immunodeficiency virus type 1 (HIV-1), and in improving the efficacy of antiretroviral therapies for the treatment of patients with the acquired immunodeficiency syndrome (AIDS). The pharmacological properties of new drugs are very effective in establishing a long-term suppression of HIV-1 replication, and have remarkably increased the survival period of patients with AIDS. However, current antiretroviral therapies are still far from eradicating HIV-1 from patients, and do not prevent the development of AIDS-related malignancies, which affect 40% of individuals infected by HIV-1. The malignancies that are considered AIDS-related are: Kaposi's sarcoma, non-Hodgkin lymphoma, intraepithelial cervical carcinoma and anal neoplasia. Their incidence is expected to increase as the survival period of patients with AIDS lengthens. Also, the cost of antiretroviral therapies poses a limit to the development of successful global intervention to tackle the worldwide spreading of AIDS, that, by the year 2000, will affect 40 million individuals. Some 90% of these new infections are occurring in developing countries, which can not afford the cost of antiretroviral therapies, and are not able to ensure a proper follow up of patients with AIDS. In addition, cultural and ethical problems make difficult the achievement of an adequate education of how to prevent the spreading of AIDS among populations of poorer countries. On these grounds, the field of AIDS research is evaluating alternative therapeutic approaches for the treatment and prevention of AIDS.
 ...
PMID:The standpoint of AIDS research and therapy programs. 971 60

In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.
 ...
PMID:AIDS-related malignancies. 978 31

Vpr, an accessory gene of HIV-1, induces cell cycle abnormality with accumulation at G2/M phase and increased ploidy. Since abnormality of mitotic checkpoint control provides a molecular basis of genomic instability, we studied the effects of Vpr on genetic integrity using a stable clone, named MIT-23, in which Vpr expression is controlled by the tetracycline-responsive promoter. Treatment of MIT-23 cells with doxycycline (DOX) induced Vpr expression with a giant multinuclear cell formation. Increased micronuclei (MIN) formation was also detected in these cells. Abolishment of Vpr expression by DOX removal induced numerous asynchronous cytokinesis in the multinuclear cells with leaving MIN in cytoplasm, suggesting that the transient Vpr expression could cause genetic unbalance. Consistent with this expectation, MIT-23 cells, originally pseudodiploid cells, became aneuploid after repeated expression of Vpr. Experiments using deletion mutants of Vpr revealed that the domain inducing MIN formation as well as multinucleation was located in the carboxy-terminal region of Vpr protein. These results suggest that Vpr induces genomic instability, implicating the possible role in the development of AIDS-related malignancies.
 ...
PMID:Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1. 1009 23

We evaluated recent trends in the incidence of AIDS-related malignancies using Cox proportional hazards analysis in 622 men with well-characterized dates of HIV seroconversion in the San Francisco City Clinic cohort. By the end of 1996, 182 men had been diagnosed with Kaposi's sarcoma (KS), and 45 men had been diagnosed with lymphoma. The incidence of KS dropped from 3.5 to 0 per 100 person-years between 1993 through 1995 and 1996 (p = .07), whereas lymphoma incidence remained stable between these periods (1.4-1.8, p = .2). Combination antiretroviral therapy increased from 13% to 23% in 1993 through 1995 to 49% in 1996 and 79% in 1997. The decline in KS cannot be explained by earlier declines in HIV incidence, and concurrent increases in antiretroviral therapy suggests that control of viral replication may lead to a direct or indirect effect on KS pathogenesis. Failure to see such a trend for AIDS-related lymphoma may reflect inadequate follow-up time after widespread use of therapy or a need to treat earlier in the course of HIV infection to prevent HIV-associated lymphomagenesis.
 ...
PMID:Combination antiretroviral therapy and incidence of AIDS-related malignancies. 1043 Feb 14

Combination anti-retroviral therapy for HIV disease has profoundly altered the nature of the AIDS epidemic. Mitigating the impact of an uncontrollable decline in immune function is no longer the focal point for AIDS therapy, but has evolved to an emphasis on maximizing the potential for immune regeneration. Improved control of HIV replication has diminished, albeit unevenly, the frequency of AIDS-related malignancies and has altered the focus of hematologic and oncologic interventions in HIV disease. Now, with adoptive cellular therapies and the genetic engineering of cells in the clinical arena, the potential for cellular therapeutics in enhancing immune restoration is being tested. These approaches are based on better understanding of the immunobiology of HIV and its impact on hematopoietic tissues.
 ...
PMID:Immune reconstitution in AIDS: oncologic implications and hematologic approaches. 1055 15

Productive high-titer infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile reverse transcripts and lack of viral progeny formation. An interplay between Tat and p53 has previously been reported, where Tat inhibited the transcription of the p53 gene, which may aid in the development of AIDS-related malignancies, and p53 expression inhibited HIV-1 long terminal repeat transcription. Here, by using a well-defined and -characterized stress signal, gamma irradiation, we find that upon gamma irradiation, HIV-1-infected cells lose their G(1)/S checkpoints, enter the S phase inappropriately, and eventually apoptose. The loss of the G(1)/S checkpoint is associated with a loss of p21/Waf1 protein and increased activity of a major G(1)/S kinase, namely, cyclin E/cdk2. The p21/Waf1 protein, a known cyclin-dependent kinase inhibitor, interacts with the cdk2/cyclin E complex and inhibits progression of cells into S phase. We find that loss of the G(1)/S checkpoint in HIV-1-infected cells may in part be due to Tat's ability to bind p53 (a known activator of the p21/Waf1 promoter) and sequester its transactivation activity, as seen in both in vivo and in vitro transcription assays. The loss of p21/Waf1 in HIV-1-infected cells was specific to p21/Waf1 and did not occur with other KIP family members, such as p27 (KIP1) and p57 (KIP2). Finally, the advantage of a loss of the G(1)/S checkpoint for HIV-1 per se may be that it pushes the host cell into the S phase, which may then allow subsequent virus-associated processes, such as RNA splicing, transport, translation, and packaging of virion-specific genes, to occur.
 ...
PMID:Loss of G(1)/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1. 1079 78

AIDS-related Kaposi's sarcoma (AIDS-KS), the most prevalent HIV-associated malignancy, is a debilitating, potentially fatal disease. Currently, there is a need for development of AIDS-KS therapies that are not only well tolerated, but also capable of providing sustained remission. Preclinical assessment of pharmacological parameters and therapeutic efficacies are dependent upon in vivo parameters. However, there are currently no animal KS models and mucocutaneous KS cell isolates have proved to be non-tumorigenic in animal hosts. This report describes the development of a murine model that enables in vivo transplantation of 'native' low population doubling level AIDS-KS cells from biopsy-confirmed mucocutaneous lesions. The angiogenic phenotype of in situ AIDS-KS lesions is reconstituted via controlled release of a complete angiogenic peptide, recombinant human basic fibroblast growth factor (bFGF), from locally injectable, biodegradable polylactide-co-glycolide implants. Consequential to the sustained local release of bioactive bFGF, a murine vascular network is established, which facilitates the in vivo transplantation of AIDS-KS cells. Desirable aspects of this model include: low cost murine species, transplantation of non-selected patient cells and use of animal hosts that are T cell-deficient. The transplanted human AIDS-KS cells and extensive murine vascular network create lesions that retain a striking resemblance, at both the gross and microscopic levels, to in situ AIDS-KS tumors. Because the bFGF-induced murine vascular network is analogous to the abundant vascularity present in AIDS-KS lesions, this murine model should provide an excellent vehicle for numerous clinically relevant studies, such as assessment of drug clearance at AIDS-KS lesional sites. Finally, applicability of this method is not restricted to AIDS-related malignancies. Establishment and maintenance of an extensive host vascular network should augment success rates for in vivo transplantation of numerous other human cell strains or lines.
 ...
PMID:Sustained angiogenesis enables in vivo transplantation of mucocutaneous derived AIDS-related Kaposi's sarcoma cells in murine hosts. 1096 95

AIDS-related cancer research may also lead to advances in cancer treatment in HIV-negative people. Significant findings in the treatment of AIDS-related cancers were presented at the American Society of Clinical Oncology meeting. Researchers at the Center for AIDS Research at the University of California, San Diego, found that granulocyte-colony stimulating factor (G-CSF/Neupogen) was well-tolerated when administered to patients with AIDS. G-CSF could be administered to enhance the immune system rather than having patients undergo bone marrow transplantation. Vinorelbine (Navelbine), a chemotherapeutic agent, could be effective for the treatment of HIV-positive patients with previously-treated Kaposi's sarcoma (KS), according to Dr. Domenico Erranto of the Centro Di Riferimento Oncologia, Italy. The effects of commonly-used medications, particularly immunosupressive chemotherapy agents, on HIV viral replication are unknown. Preliminary findings from the AIDS Malignancy Program at the Illinois Masonic Cancer Center in Chicago suggest that standard chemotherapeutic agents do not significantly affect HIV activity when used in combination with anti-HIV drug therapies.
 ...
PMID:New discoveries in the treatment of AIDS-related cancers. 1136 84

The first National AIDS Malignancy Conference was held sixteen years after the first outbreak of Kaposi's sarcoma (KS) was noted in the medical press. The conference was devoted to the spectrum of malignancies that occur with AIDS. Researchers were divided on whether KS is tumorigenic or not. Other controversial topics included the use of standard-dose chemotherapy in patients with late-stage HIV infection, screening and aggressive treatments used for precancerous cervical changes, the management of AIDS-related malignancies in patients who are responding well to HIV treatments, and whether some AIDS-related malignancies will be classified as AIDS-defining conditions. The Centers for Disease Control and Prevention (CDC) currently considers KS, lymphoma, and cervical cancer as AIDS-defining malignancies. Specific sections of the conference dealt with pediatric cancers, squamous cell carcinoma, testicular cancer, lung cancer, and Hodgkin's disease.
 ...
PMID:AIDS cancers: conundrums and controversies. 1136 11


<< Previous 1 2 3 4 5 6 Next >>