Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several tumor viruses, such as human T-cell leukemia virus (HTLV), human papilloma virus (HPV), human adenovirus, have high-oncogenic and low-oncogenic subtypes, and such subtype-specific oncogenesis is associated with the PDZ-domain binding motif (PBM) in their transforming proteins. HTLV-1, the causative agent of adult T-cell leukemia, encodes Tax1 with PBM as a transforming protein. The Tax1 PBM was substituted with those from other oncoviruses, and the transforming activity was examined. Tax1 mutants with PBM from either HPV-16 E6 or adenovirus type 9 E4ORF1 are fully active in the transformation of a mouse T-cell line from interleukin-2-dependent growth into independent growth. Interestingly, one such Tax1 PBM mutant had an extra amino acid insertion derived from E6 between PBM and the rest of Tax1, thus suggesting that the amino acid sequences of the peptides between PBM and the rest of Tax1 and the numbers only slightly affect the function of PBM in the transformation. Tax1 and Tax1 PBM mutants interacted with tumor suppressors Dlg1 and Scribble with PDZ-domains. Unlike E6, Tax1 PBM mutants as well as Tax1 did not or minimally induced the degradations of Dlg1 and Scribble, but instead induced their subcellular translocation from the detergent-soluble fraction into the insoluble fraction, thus suggesting that the inactivation mechanism of these tumor suppressor proteins is distinct. The present results suggest that PBMs of high-risk oncoviruses have a common function(s) required for these three tumor viruses to transform cells, which is likely associated with the subtype-specific oncogenesis of these tumor viruses.
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PMID:The PDZ domain binding motif (PBM) of human T-cell leukemia virus type 1 Tax can be substituted by heterologous PBMs from viral oncoproteins during T-cell transformation. 2006 50

Infectious agents are one of the factors which contribute to cancer development. Few examples include human papilloma virus in cervical cancer, hepatitis virus in hepatocellular carcinoma, herpes virus in Kaposi's sarcoma, Epstein-Barr virus in nasopharyngeal carcinoma, human T-cell lymphotropic virus type-1 (HTLV-1) in T-cell leukemia and lymphoma, Helicobacter pylori in gastric cancer. These agents cause genomic instability in the host and most of them affect host immune system. Infectious agents may integrate in the host genome although their sit of integration is not fixed. Expression of some infectious agents involves epigenetic regulation by DNA methylation, histone modification, miRNA level alteration, and chromatin condensation. This chapter provides examples where epigenetic regulation has been reported in cancer-associated infectious agents. Epigenetic inhibitors and their potential in cancer control and treatment are also discussed.
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PMID:Cancer-associated infectious agents and epigenetic regulation. 2542 69

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.
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PMID:Natural history of GATA2 deficiency in a survey of 79 French and Belgian patients. 2972 3

There remains today a critical need for new antiviral agents, particularly in view of the alarming increase in drug resistance and associated issues. The marine environment has been a prolific contributor towards the identification of novel therapeutic agents in the recent few decades. Added to this, glycans (or carbohydrate- or sugar-based compounds) have in very recent decades made outstanding contributions to the development of novel therapeutics. This review brings together these significant facets of modern drug discovery by presenting the reported literature on glycans derived from marine organisms that possess antiviral activity.The glycans have been grouped together based on the marine organism they were isolated from, namely, (1) bacteria, (2) chromists, (3) plants and (4) animals. For chromists, glycans are further subsectioned into Ochrophyta (brown algae), Miozoa (according to www.algaebase.org ; also called Myzozoa according to WoRMS, www.marinespecies.org ) (dinoflagellates) and Bacillariophyta (diatoms). For plants, glycans are further subsectioned into Chlorophyta, Rhodophyta and Tracheophyta. Glycans isolated to date are reported as alginates, chitosan, extracellular polysaccharides, fucans (e.g. fucoidans), galactans (e.g. carrageenans), glycolipids, glycosaminoglycans, glycosides, glycosylated haemocyanin, laminarans, mannans, polysaccharides (not defined), rhamnans and xylomannans. Interestingly, many of the glycans displaying antiviral properties are sulfated.Reports indicate that marine-sourced glycans have exhibited antiviral activity against African swine fever virus, cytomegalovirus, dengue virus, Epstein-Barr virus, encephalomyocarditis virus, human immunodeficiency virus, hepatitis C virus, herpes simplex virus, human cytomegalovirus, human papilloma virus, human rhino virus, influenza virus, Japanese encephalitis virus, murine leukaemia virus, murine sarcoma virus, Newcastle disease virus, parainfluenza virus, respiratory syncytial virus, Semliki Forest virus, tobacco mosaic virus, vaccinia virus, varicella zoster virus, viral haemorrhagic septicaemia virus and vesicular stomatitis virus. Selected representative glycan structures are presented in Fig. 20.1.
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PMID:Glycans with Antiviral Activity from Marine Organisms. 3008 31

Most chronic viruses evade T-cell and natural killer (NK) immunity through downregulation of immune surface markers. Previously we showed that Pomalidomide (Pom) increases surface expression of major histocompatibility complex class I (MHC-I) in Kaposi sarcoma-associated herpesvirus-infected latent and lytic cells and restores ICAM-1 and B7-2 in latent cells. We explored the ability of Pom to increase immune surface marker expression in cells infected by other chronic viruses, including human T-cell leukemia virus type-1 (HTLV-1), Epstein-Barr virus (EBV), human papilloma virus (HPV), Merkel cell polyoma virus (MCV), and human immunodeficiency virus type-1 (HIV-1). Pom increased MHC-1, ICAM-1, and B7-2/CD86 in immortalized T-cell lines productively infected with HTLV-1 and also significantly increased their susceptibility to NK cell-mediated cytotoxicity. Pom enhancement of MHC-I and ICAM-1 in primary cells infected with HTLV-1 was abrogated by knockout of HTLV-1 orf-1. Pom increased expression of ICAM-1, B7-2 and MHC class I polypeptide related sequence A (MICA) surface expression in the EBV-infected Daudi cells and increased their T-cell activation and susceptibility to NK cells. Moreover, Pom increased expression of certain of these surface markers on Akata, Raji, and EBV lymphoblastic cell lines. The increased expression of immune surface markers in these virus-infected lines was generally associated with a decrease in IRF4 expression. By contrast, Pom treatment of HPV, MCV and HIV-1 infected cells did not increase these immune surface markers. Pom and related drugs may be clinically beneficial for the treatment of HTLV-1 and EBV-induced tumors by rendering infected cells more susceptible to both innate and adaptive host immune responses.
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PMID:Pomalidomide increases immune surface marker expression and immune recognition of oncovirus-infected cells. 3071 8

Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regression following treatment; therefore, CSCs are associated with a poor prognosis. CSCs have been detected in many types of cancer, including leukemia, pancreatic, colon, esophagus, liver, prostate, breast, gastric and lung cancer. In cervical cancer, CSCs have been associated with resistance to normally used drugs such as cisplatin. The present review summarizes the strategies that high-risk HPV viruses (HPV-16 and HPV-18) have developed to transform normal epithelial cells into cancer cells, as well as the cellular pathways and studies associated with the identification of cervical cancer stem cell biomarkers. In this sense, the present review provides state of the art information regarding CC development.
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PMID:Cervical cancer stem cells and other leading factors associated with cervical cancer development. 3151 60


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