Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer remains a significant burden for human immunodeficiency virus (HIV)-infected individuals. Most cancers that are associated with HIV infection are driven by oncogenic viruses, such as Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus and human papillomavirus. Gaining insight into the epidemiology and mechanisms that underlie AIDS-related cancers has provided us with a better understanding of cancer immunity and viral oncogenesis.
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PMID:AIDS-related malignancies. 1204 13

The relationship between Epstein Barr Virus (EBV) and the human host is commonly benign, whereas the development of malignancy is most likely due to imbalance between the virus and host's immune system. The aim of this study was to analyze the association of EBV with pediatric lymphomas in human immunodeficiency virus (HIV) patients. Four consecutive patients with a histological and clinical diagnosis of lymphomas among 351 pediatric HIV-infected children prospectively followed up at our hospital since 1991 were studied. The cases included one diffuse fibrosis lymphocyte depletion subtype Hodgkin's lymphoma, 2 Burkitt's lymphomas, and one primary diffuse large B-cell lymphoma of the central nervous system. We assessed EBV presence by LMP-1 protein labeling by immunohistochemistry and in situ hybridization for EBERs in formalin-fixed and paraffin-embedded biopsies from all four cases. All HIV-associated lymphomas studied were found to be associated with EBV. The lymphoproliferative action of EBV may induce oncogenesis by increasing the probability of genetic alterations and/or by expanding an already malignant clone. As an oncogenic protein, LMP-1 expression by tumor cells supports the involvement of EBV in disease pathogenesis.
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PMID:Epstein Barr virus-associated lymphoma in HIV-infected children. 1209 68

DNA methylation regulates important biological processes and is involved in tumorigenesis and several human diseases, such as Rett and immunodeficiency, centromeric instability and facial anomalies (ICF). The major objective of our research is to investigate the roles of DNA methylation in mammals through genetic analysis of DNA methyltransferase genes in mouse and human. Previously, we found that Dnmt1 knockout embryonic stem (ES) cells are capable of methylating retroviral DNA de novo. In search of enzymes responsible for de novo methylation, we have cloned a novel family of mammalian DNA methyltransferase genes, Dnmt3a and Dnmt3b. Although extensive sequence similarity was found between Dnmt3a and Dnmt3b, little homology was observed between Dnmt1 and Dnmt3a/3b in the catalytic domain as well as in the N-terminal domain. Additionally, biochemical analysis revealed that, unlike Dnmt1, neither Dnmt3a nor Dnmt3b had a strong preference to hemimethylated DNA substrates. Genetic analysis demonstrated that Dnmt3a and Dnmt3b were required for de novo methylation activities in ES cells and during early embryogenesis and were essential for early development. Interestingly, phenotype analyses of single homozygous mice for either Dnmt3a or Dnmt3b suggested that the functions of Dnmt3a and Dnmt3b also were required at the late developmental stage and even at the adult stage.
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PMID:Genetic analyses of DNA methyltransferase genes in mouse model system. 1216 12

The Tat protein of the human immunodeficiency virus type 1 promotes survival and growth and inhibits apoptosis of different cell types. These effects of Tat are attributed to the induction of bcl-2 gene expression. In this study we show that the blocking of both intracellular and extracellular Tat correlates with a decrease of bcl-2 transcripts, leading in vitro to a lower growth rate and attenuation of the transformed phenotype and in vivo to a reduced angiogenic and oncogenic activity of Tat-expressing cells. These results support the notion that bcl-2 is an effector of Tat-induced angiogenesis and oncogenesis and indicate that the blocking of Tat functions by immunoprophylactic, pharmacological, and gene therapy approaches may help to control oncogenesis during AIDS.
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PMID:Inhibition of HIV-1 Tat activity correlates with down-regulation of bcl-2 and results in reduction of angiogenesis and oncogenicity. 1216 35

In this study we examined 21 cases of AIDS-related lymphomas for genomic organization and expression of RB2/p130 oncosuppressor gene and compared the results with the proliferative features of these neoplasms. We found no mutations in the RB2/p130 gene and unusually high percentages of cells expressing nuclear pRb2/p130 in tumors with a high proliferative activity, such as AIDS-related lymphomas. These findings might suggest that a molecular mechanism usually observed in viral-linked oncogenesis could be involved. We performed in vitro and in vivo binding assays to investigate whether the human immunodeficiency virus (HIV) gene product Tat and Rb2/p130 could interact. The results of these assays revealed that the HIV-1 Tat protein binds specifically to pRb2/p130. This may result in the inactivation of its oncosuppressive properties and the induction of genes needed to proceed through the cell cycle including p107, cyclin A, and cyclin B. Using single-cell polymerase chain reaction (PCR) assay, we found HIV-1 DNA in the neoplastic cells of only 2 of the 21 cases examined, whereas PCR on whole tissue revealed HIV-1 DNA in all of the cases. Furthermore, a diffuse and nuclear stain was observed in tissue sections with anti-Tat monoclonal antibody. These findings are in accordance with the notion that soluble Tat protein could function as a biologically active extracellular protein released by infected cells and taken up readily by uninfected B cells. In conclusion, our results seem to suggest that pRb2/p130 oncosuppressor protein may be a target in the interaction between the HIV-1 gene products and host proteins.
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PMID:Expression of RB2/p130 tumor-suppressor gene in AIDS-related non-Hodgkin's lymphomas: implications for disease pathogenesis. 1219 24

Kaposi sarcoma-associated herpesvirus (KSHV) is a recently discovered and characterized member of the herpesvirus family. It is one of a few viruses proved to be associated with tumorigenesis in humans. Its causal association with 4 clinical and epidemiologic variants of Kaposi sarcoma (classic, endemic, iatrogenic, and acquired immunodeficiency virus-associated) as well as with several lymphoproliferative disorders (notably primary effusion lymphoma and multicentric Castleman disease) is reviewed critically. Issues related to the epidemiology, transmission, and molecular and serologic diagnosis are discussed. Several intriguing oncogenic mechanisms of KSHV infection have been identified. These are often dependent on the interaction of KSHV with other viruses, such as human immunodeficiency virus, Epstein-Barr virus, or both. However, important problems remain and once resolved will substantially enhance our understanding of oncogenesis in general and viral-induced oncogenesis in particular. This may also translate into improved treatment and perhaps prevention of this common and intriguing viral infection.
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PMID:Virology, pathogenetic mechanisms, and associated diseases of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8). 1223 27

Central nervous system leiomyosarcomas are extremely rare, however, they became more frequent among immunodeficient patients, either in a patients infected with human immunodeficiency virus (HIV), or after organ transplantation. The data of the literature indicate that the infection by Epstein-Barr virus (EBV) plays a causal role in the development of these tumours but its precise role in the oncogenesis remains unresolved. We report a new case of EBV associated leiomyosarcoma of the left cavernous sinus occurring after renal transplantation. The epidemiological, clinical, pathological and therapeutic characteristics of these tumours are discussed.
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PMID:[Epstein-Barr virus associated central nervous system leiomyosarcoma occurring after renal transplantation: case report and review of the literature]. 1452 51

The human immunodeficiency virus type 1 (HIV-1) Tat protein stimulates cell proliferation, inhibits apoptosis, displays angiogenic functions and is believed to be involved in the pathogenesis of Kaposi's sarcoma (KS) and other tumours arising in AIDS patients. Tat-transgenic (TT) mice, which constitutively express Tat in all tissues and organs, may therefore be predisposed to tumorigenesis. To test this hypothesis, we treated TT mice with urethane, a general carcinogen inducing tumours of various organs. The results indicate that, after injection of urethane, the incidence of lung tumours and lymphomas is not significantly different in the TT and control (CC) mice, whereas liver preneoplastic lesions and tumours show a significantly greater incidence in TT than in CC mice. This remarkable carcinogenic effect of urethane for the liver may be due to a tat-induced predisposition, manifested as a liver cell dysplasia (LCD), spontaneously affecting most of the TT mice. LCD may exert a promoting effect by stimulating proliferation of cell clones initiated by the mutagenic effect of urethane. In addition, LCD, which is associated with aneuploidy and chromosome instability, may enhance the progression to malignancy of the preneoplastic lesions induced by urethane. Interestingly, a significantly greater incidence of vascular ectasias and haemangiomas was detected in the liver of urethane-treated TT mice, most likely due to the marked angiogenic properties of Tat. This study suggests a role for Tat in the promotion and progression of tumours initiated by exogenous and endogenous carcinogens in HIV-1-infected patients, thereby contributing to the tumorigenesis in the course of AIDS.
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PMID:Prevalence of liver tumours in HIV-1 tat-transgenic mice treated with urethane. 1472 43

The importance of the IkappaB kinase (IKK)/NF-kappaB signaling pathway in immunoregulatory functions is well accepted. However, the relevance of IKK and NF-kappaB in tumor maintenance, tumor promotion and possibly even in tumor initiation is becoming more evident. Activation of the IKK/NF-kappaB signaling pathway leads to the induction of target genes that can interfere with apoptosis, cell cycle regulation, cell invasion and metastatic growth as well as radio- and chemotherapy. By possibly bridging inflammation and cancer NF-kappaB might also contribute to tumorigenesis. Several natural compounds and synthetic drugs that are able to inhibit the IKK/NF-kappaB activation pathway have been shown to either prevent cancer or to inhibit cell growth in animal models. However, these compounds do not selectively inhibit any of the NF-kappaB activation pathways. Furthermore, general inhibition of NF-kappaB might lead to immunodeficiency. The investigation of the different NF-kappaB signaling pathways in different cell types and their role in certain diseases is therefore needed to evaluate the most successful therapeutic strategies.
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PMID:The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer. 1501 24

ATM protein anticipates in the initiation of the DNA repair signal pathway and also mediates cell cycle arrest and repair. ATM deficiency predictably results in radiosensitivity, germ cell degeneration, chromosomal instability, immunodeficiency, and an extreme predisposition to tumors. Moreover, studies found that ATM is the upstream gene of the p53 pathway and would phosphorylate p53 directly after DNA damage, which would suppress tumorigenesis. Expression of ATM and p53 in 167 pancreatic cancer and 101 control specimens, benign lesions, and normal pancreata were detected by high-throughput tissue microarray and immunohistochemistry while seeking the role of ATM in the initiation and development of pancreatic carcinoma as well as its relationship with p53. We found that the positive rates of ATM and p53 expression in pancreatic carcinoma and its relative control specimen were 67.7% (113/167) and 82.2% (83/101) (P < 0.05) and 57.5% (96/167) and 5.0% (5/101) (P < 0.01), respectively. ATM positive staining is significantly relative to age and infiltration (P < 0.05), while the expression of p53 was significantly associated with tumor differentiation, lymph node metastasis, and nerve infiltration (P < 0.05). Expression of ATM and p53 was positively correlated. These findings suggest that expression of ATM deficiency may increase the transformative ability of pancreatic cancer cells. ATM may also cooperate with p53 in the repair of cell damage.
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PMID:Expression of ATM protein and its relationship with p53 in pancreatic carcinoma with tissue array. 1509 60


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