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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the advent of Highly-Active-Anti-Retroviral-Therapy (HAART), HIV patients can expect to live beyond 10-15 years following diagnosis. An unexpected result of increased survival is the emergence of opportunistic, oncogenic virus-associated cancers such as Burkitt's lymphoma (Epstein-Barr Virus), cervical cancer (Human Papilloma Virus) and Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus) in this immuno-compromised population. Furthermore, there are reports of colorectal cancers (CRC) in long-term HIV-AIDS survivors. Compared to the general, non-immuno-compromised population, long-term AIDS patients have 4 and 3.3-fold increased risk of developing colorectal and anorectal cancer respectively. Unlike oncogenic virus-associated cancers, CRC is not known to have a viral etiology. Our study aimed to investigate one aspect of HIV infection and colorectal carcinogenesis. We proposed that the HIV transactivator protein Tat; a protein with known oncogenic properties that is secreted and can re-enter non-infected cells may have a role in CRC. Using two CRC cell lines, LIM1215 and LIM2537 we found that Tat inhibits epithelial cyto-differentiation, blocks apoptosis in vitro and accelerates tumour formation in vivo. In addition, Tat significantly increases in vitro migration in the absence of foetal calf serum. These properties underpin CRC, and as HIV infection is initiated in the gut lymphoid system, these data provide a basis for the increased incidence of CRC in long term AIDS patients.
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PMID:Oncogenic properties of HIV-Tat in colorectal cancer cells. 1762 3

The skin is an organ in which direct contact with viruses, solar UV irradiation and increased susceptibility to immune suppression gather to support viral tumorigenesis. Viruses transform keratinocytes by activation of cancer-promoting genes. Viral proteins may directly act as oncogenes that drive cells to proliferate or generate inflammatory responses and cause regeneration of injured cells that eventually lead to malignant transformation. Accelerated viral carcinogenesis is observed in the immune-deficient host. Decreased T-cell reactivity and lower number of antigen-presenting cells in the skin assist in viral escape and emergence of skin tumors. Three pathogenic human viruses associated with skin neoplasms are described: human papilloma virus (HPV), Kaposi's sarcoma (KS)-associated herpesvirus and human T-cell leukemia virus type 1. HPV was linked to squamous cell carcinoma (SCC) of the skin after its role in SCC of the cervix has been discovered. In the rare autosomal recessive epidermodysplasia verruciformis, an increased susceptibility to specific HPV strains initially results in widespread wart infection and later in life in the development of SCC over the sun-exposed skin. The role of HPV in nonmelanoma skin cancer of immune competent hosts is more difficult to prove. The discovery of human herpesvirus 8 as the causative pathogen of KS was made following the AIDS epidemic, and its role in all clinical variants of this tumor was confirmed. KS-associated herpesvirus exerts its tumorigenic effect through a wide repertoire of genes that regulate angiogenesis, inflammation, and cell cycle. Human T-cell leukemia virus type 1 causes adult T-cell leukemia and is often associated with skin eruptions that share common features with cutaneous T-cell lymphoma. In summary, studies of oncogenic viruses shed light on molecular mechanisms leading to tumor formation and aid in recognition of new pathways of carcinogenesis.
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PMID:Viral carcinogenesis in skin cancer. 1764 89

Controversy is associated with the issue of cannabis and cannabinoids in clinical care in the United States. Recent research has demonstrated the underlying mechanisms of cannabinoid analgesia via endocannabinoids, an endogenous system of retrograde neuromodulatory messengers that work in tandem with endogenous opioids. Additional receptor and non-receptor mechanisms of cannabinoid drugs have pertinent activity, including anti-carcinogenesis and neuroprotection, that may be of key importance in aging and terminal patient populations. The results of clinical trials with synthetic and plant-based cannabinoids suggest that the role of formulation and delivery system is critical in optimizing the risk-benefit profile of cannabinoid products. Synergy between opioids and cannabinoids may produce opioid-sparing effects, as well as extend the duration of analgesia and reduce opioid tolerance and dependence. This article reviews the mechanism of action of cannabinoids, examines marketed agents and those in clinical trials, and addresses their role in treatment of chronic pain, cancer, neurodegenerative diseases, and HIV/ AIDS. The ability of cannabinoid medicines to treat pain, associated sleep disorders, appetite loss, muscle spasm and a wide variety of other symptoms suggests that such agents may in the future play an important role in palliative care.
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PMID:Cannabinoids:their role in pain and palliation. 1803 52

Recently, research of stem cells has garnered great attention and has shown promise by changing the view of traditional therapeutics, with broad impact on gene therapy, carcinogenesis, organ development, tissue injury, regeneration and almost all aspects of the life cycle and all living systems. A century's scientific progress has significantly improved controls for infectious diseases and many other disorders. However, many remaining problems (i.e. cancer, AIDS, diabetes, Parkinson's disease and Marburg infection) appear to be even harder than those that have already been solved. In particular, respiratory stem cell research has been less active and has moved more slowly than that of many other organs. This is probably due to the complexity of the lung and airway system, particularly owing to the many types of cells (>40), unique structures and functions, and technical difficulty in analyzing this system at the genetic, biochemical, molecular and cellular level. Compared with other epithelial cells (i.e., gastrointestinal epithelium), respiratory epithelia have a very low turnover rate and minimal regenerative activity. This review will discuss the current state of pulmonary stem cells, their origin, development, differentiation, and regenerative application, with a particular focus on potential impact on cancer development and lung injury repair.
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PMID:Respiratory stem cells and progenitors: overview, derivation, differentiation, carcinogenesis, regeneration and therapeutic application. 1822 Aug 52

The current incidence of human immunodeficiency virus (HIV-1)/AIDS affects around 7000 pregnant women in the United States. When given during pregnancy, the nucleoside analog 3'-azido-3'-deoxythymidine (AZT) significantly reduces maternal-fetal transmission. It has been previously shown that AZT is incorporated into DNA, where it causes mutations in the HPRT and TK genes. It also changes cell cycle gene expression, and induces S-phase arrest, micronuclei, chromosomal aberrations, sister chromatid exchanges, telomeric attrition, and other genotoxic effects in cultured cells. A predicted consequence of these events is genomic instability that together, with clastogenicity may contribute to the carcinogenic potency of AZT. Various aspects of genotoxicity are explored in this contribution seeking to understand the multiple effects of this antiretroviral agent in animal models and humans. This mini-review describes some of the experimental models used to elucidate the genotoxicity induced by antiretroviral therapy during human pregnancy. The use of diverse methods to detect biomarkers of exposure, such as an AZT-specific radioimmunoassay, micronuclei bearing intact chromosomes, and telomeric DNA attrition highlight the role of in vitro models to elucidate exposure and risk. The relevance of the in vitro models is followed by the introduction of the role of the nucleoside analogs in transplacental carcinogenesis along with the description of a transplacental perfusion model and a transplacental carcinogenesis rodent model. In a more direct clinical application the use of AZT-DNA incorporation as a biomarker of exposure, in experiments conducted in vivo in Erythrocebus patas monkeys and in humans, addresses the possibility of elucidation of potential cancer risk in those infants exposed in utero. Two relevant aspects of this contribution are the potential application of some of the models described in this mini-review, as diagnostic tools in antiretroviral-exposed populations, and the use of these models to understand the nature of the genotoxicities and minimize the undesirable side effects of the antiretroviral therapy.
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PMID:Relevance of experimental models for investigation of genotoxicity induced by antiretroviral therapy during human pregnancy. 1829 33

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis. This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.
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PMID:HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier? 1857 46

Cancer is one of the most common causes of morbidity and mortality today. It is estimated that around 43% of cancer deaths are due to tobacco use, unhealthy diets, alcohol consumption, inactive lifestyles and infection. Low-income and disadvantaged groups are generally more exposed to avoidable risk factors such as environmental carcinogens, alcohol, infectious agents, and tobacco use. These groups also have less access to the health services and health education that would empower them to make decisions to protect and improve their own health. Oro-pharyngeal cancer is significant component of the global burden of cancer. Tobacco and alcohol are regarded as the major risk factors for oral cancer. The population-attributable risks of smoking and alcohol consumption have been estimated to 80% for males, 61% for females, and 74% overall. The evidence that smokeless tobacco causes oral cancer was confirmed recently by the International Agency for Research on Cancer. Studies have shown that heavy intake of alcoholic beverages is associated with nutrient deficiency, which appears to contribute independently to oral carcinogenesis. Oral cancer is preventable through risk factors intervention. Prevention of HIV infection will also reduce the incidence of HIV/AIDS-related cancers such as Kaposi sarcoma and lymphoma. The WHO Global Oral Health Programme is committed to work for country capacity building in oral cancer prevention, inter-country exchange of information and experiences from integrated approaches in prevention and health promotion, and the development of global surveillance systems for oral cancer and risk factors. The WHO Global Oral Health Programme has established a global surveillance system of oral cavity cancer in order to assess risk factors and to help the planning of effective national intervention programmes. Epidemiological data on oral cancer (ICD-10: C00-C08) incidence and mortality are stored in the Global Oral Health Data Bank. In 2007, the World Health Assembly (WHA) passed a resolution on oral health for the first time in 25 years, which also considers oral cancer prevention. The resolution WHA60 A16 URGES Member states--To take steps to ensure that prevention of oral cancer is an integral part of national cancer-control programmes, and to involve oral-health professionals or primary health care personnel with relevant training in oral health in detection, early diagnosis and treatment;--The WHO Global Oral Health Programme will use this statement as the lead for its work for oral cancer control www.who.int/oral_health.
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PMID:Oral cancer prevention and control--the approach of the World Health Organization. 1880 12

Oral health is an integral component of general health and well being and a basic human right. Dental public health is probably the most challenging specialty of dentistry. Because of the lack of adequate resources among other factors, many people are likely to suffer from dental diseases. Despite great improvements in the oral health status of populations across the world, the burden and impact of dental diseases are still high. This is particularly true among underprivileged groups in both developed and developing communities. Oral diseases and conditions, including oral cancer, oral manifestations of HIV/AIDS, dental trauma, craniofacial anomalies, and noma, all have broad impacts on health and well-being. Oral cancer, the sixth most common cancer worldwide continues to be most prevalent cancer related to the consumption of tobacco, alcohol and other carcinogenic products. Nevertheless, significant reduction in mortality can be achieved by advances in early diagnosis and implementation of multidisciplinary treatment programs leading to improvement of survivorship and better quality of life. The present study was designed to evaluate the immunologic and biochemical markers in oral carcinogenesis using circulating immune complexes (CIC), copper, iron, and selenium concentrations as assessment endpoints. Study results indicated an increase in CIC and copper levels, and a decrease in iron and selenium concentrations in oral cancer patients compared to controls. The implications of these findings for public health are discussed.
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PMID:Immunological and biochemical markers in oral carcinogenesis: the public health perspective. 1915 37

Kaposi's sarcoma (KS) is the major AIDS-associated malignancy. It is characterized by the proliferation of spindle cells, inflammatory infiltrate, and aberrant angiogenesis caused by Kaposi's sarcoma herpesvirus (KSHV) infection. Small GTPase Rac1, an inflammatory signaling mediator triggering reactive oxygen species (ROS) production by NADPH-oxidases, is implicated in carcinogenesis and tumor angiogenesis. Here, we show that expression of a constitutively active Rac1 (RacCA) driven by the alpha-smooth muscle actin promoter in transgenic mice is sufficient to cause KS-like tumors through mechanisms involving ROS-driven proliferation, up-regulation of AKT signaling, and hypoxia-inducible factor 1-alpha-related angiogenesis. RacCA-induced tumors expressed KS phenotypic markers; displayed remarkable transcriptome overlap with KS lesions; and were, like KS, associated with male gender. The ROS scavenging agent N-acetyl-cysteine inhibited angiogenesis and completely abrogated transgenic RacCA tumor formation, indicating a causal role of ROS in tumorigenesis. Consistent with a pathogenic role in KS, immunohistochemical analysis revealed that Rac1 is overexpressed in KSHV(+) spindle cells of AIDS-KS biopsies. Our results demonstrate the direct oncogenicity of Rac1 and ROS and their contribution to a KS-like malignant phenotype, further underscoring the carcinogenic potential of oxidative stress in the context of chronic infection and inflammation. They define the RacCA transgenic mouse as a model suitable for studying the role of oxidative stress in the pathogenesis and therapy of KS, with relevance to other inflammation-related malignancies. Our findings suggest host and viral genes triggering Rac1 or ROS production as key determinants of KS onset and potential KS chemopreventive or therapeutic targets.
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PMID:Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. 1979 64

Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1) was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.
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PMID:Persistent exposure to Mycoplasma induces malignant transformation of human prostate cells. 1972 14


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