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

Persistent human papillomavirus (HPV) infection seems central to cervical carcinogenesis. Smoking is associated with cervical cancer in HPV DNA-positive women, but its association with HPV persistence is unclear, particularly with respect to human immunodeficiency virus (HIV) serostatus. The authors evaluated smoking and HPV clearance by HIV serostatus among 801 women from the HIV Epidemiology Research Study (United States, 1993-2000). Type-specific HPV duration was defined as the interval between initial MY09/11 polymerase chain reaction positivity and the first of two consecutive HPV-negative study visits. Hazard ratios adjusted for study site and risk behaviors (sexual activity or injection drug use) were estimated using Cox regression. This analysis included 522 HIV-seropositive and 279 HIV-seronegative women (median follow-up, 4.4 years). Ever smoking was associated with reduced clearance of high-risk HPV in HIV-seronegative women (hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.30, 0.88) but not in HIV-seropositive women (HR = 0.96, 95% CI: 0.65, 1.42); similar results were found for current smoking. Current smoking was not associated with clearance of any type-specific HPV in HIV-seropositive (HR = 0.99, 95% CI: 0.82, 1.20) or HIV-seronegative (HR = 0.93, 95% CI: 0.68, 1.26) women. HPV clearance did not appear to vary by amount or duration of smoking. Smoking did not modify overall clearance but was associated with lower high-risk HPV clearance in HIV-seronegative women.
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PMID:Smoking and time to clearance of human papillomavirus infection in HIV-seropositive and HIV-seronegative women. 1677 41

Hereditary human disorder ataxia telangiectasia (AT) is characterized by an extremely high incidence of lymphoid malignancies, neuromotor dysfunction, immunodeficiency and radiosensitivity. Cells from AT patients show genetic instability and a continuous state of oxidative stress. We examined the effect of long-term dietary supplementation with the thiol-containing antioxidant, N-acetyl-L-cysteine (NAC), on survival and cancer formation in Atm (AT-mutated) deficient mice, used as an animal model of AT. NAC was chosen because it is well-tolerated in animals and humans. It can be used by the oral route and for long-term at high concentrations. In addition, NAC suppresses carcinogenesis-associated biological markers in Atm deficient mice, such as DNA deletions and oxidative DNA damage (R. Reliene, E. Fischer, R.H. Schiestl, Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice, Cancer Res. 64 (2004) 5148-5153). In this study, NAC significantly increased the lifespan and reduced both the incidence and multiplicity of lymphoma in Atm deficient mice. The life span increased from 50 to 68 weeks and the incidence of lymphoma decreased by two-fold (76.5% versus 37.5%). Moreover, in mice with lymphoma, multiplicity of tumors decreased from 4.6 to 2.8 tumors per mouse. Thus, dietary supplementation with NAC may turn out to be protective against lymphomagenesis in AT patients.
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PMID:Antioxidant N-acetyl cysteine reduces incidence and multiplicity of lymphoma in Atm deficient mice. 1678 Nov 97

The human genetic disorder, Nijmegen breakage syndrome (NBS), is characterized by radiosensitivity, immunodeficiency and an increased risk for cancer, particularly B-cell non-Hodgkin lymphoma. The NBS1 gene codes for a protein, nibrin, involved in the processing/repair of DNA double-strand breaks and in cell cycle checkpoints. The majority of patients are homozygous for a founder mutation, a 5 bp deletion. This mutation is actually hypomorphic, since a functionally relevant truncated protein, of approximately 70 kDa, is produced by alternative translation. Null mutation of the homologous gene in mice is lethal; however, null-mutant murine cells can be rescued by a human NBS1 cDNA carrying the founder mutation. Clearly, the truncated p70-nibrin is able to sustain vital cellular functions of the full-length protein. We have used semi-quantitative immunoprecipitation to examine a panel of 26 lymphoblastoid B-cell lines from NBS patients for their level of p70-nibrin expression and correlate this with details of clinical phenotype provided by the two contributing centres. We find considerable variation in the amount of p70-nibrin in cell lines from different patients. Examination of clinical history indicated a clear and statistically significant correlation between p70-nibrin expression levels and lymphoma incidence. The variation in p70-nibrin levels between patients probably reflects the susceptibility of the alternative translation process to other genetic and non-genetic factors. Patients whose cells are able to maintain particularly high levels of the truncated p70-nibrin protein are at a lower risk for lymphoma than those patients with low levels of p70-nibrin in their cells.
Carcinogenesis 2007 Jan
PMID:Cancer incidence in Nijmegen breakage syndrome is modulated by the amount of a variant NBS protein. 1684 Apr 38

Damaging DNA double-strand breaks (DNA-DSBs) following ionizing radiation (IR) exposure, potentially lead to cell death or carcinogenesis. Non-homologous end-joining (NHEJ) is the main repair pathway employed by vertebrate cells to repair such damage. Many repair pathway proteins have been identified. The creation of many diverse lymphocyte receptors to identify potential pathogens has evolved by breaking and randomly re-sorting the gene segments coding for antigen receptors. Subsequent DNA-DSB repair utilizes the NHEJ proteins. Individuals with defective repair pathways are increasingly recognized with radiosensitivity and immunodeficiency. Patients with defects in ataxia-telangiectasia mutated, nibrin, MRE11, Rad50, Artemis, DNA ligase IV and Cernunnos-XRCC4-like factor have been identified. Most exhibit immunodeficiency, with a spectrum of presentation and overlap between conditions. Conventional treatment with immunoglobulin replacement or haematopoietic stem cell transplantation (HSCT) can be effective. A greater understanding of the molecular defect will enable better, tailored therapies to improve survival.
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PMID:Primary immunodeficiency syndromes associated with defective DNA double-strand break repair. 1697 55

Astragalus memebranaceus is used as immunomodulating agent in treating immunodeficiency diseases and to alleviate the adverse effects of chemotherapeutic drugs. In recent years, it has been proposed that Astragalus may possess anti-tumorigenic potential in certain cancer cell types. In this study, the anti-carcinogenic effects of Astragalus saponin extract were investigated in HT-29 human colon cancer cells and tumor xenograft. Our findings have shown that Astragalus saponins (AST) inhibit cell proliferation through accumulation in S phase and G2/M arrest, with concomitant suppression of p21 expression and inhibition of cyclin-dependent kinase activity. Besides, AST promotes apoptosis in HT-29 cells through caspase 3 activation and poly(ADP-ribose) polymerase cleavage, which is indicated by DNA fragmentation and nuclear chromatin condensation. Nevertheless, we also demonstrate the anti-tumorigenic effects of AST in vivo, of which the reduction of tumor volume as well as pro-apoptotic and anti-proliferative effects in HT-29 nude mice xenograft are comparable with that produced by the conventional chemotherapeutic drug 5-fluorouracil (5-FU). In addition, the side effects (body weight drop and mortality) associated with the drug combo 5-FU and oxaliplatin are not induced by AST. These results indicate that AST could be an effective chemotherapeutic agent in colon cancer treatment, which might also be used as an adjuvant in combination with other orthodox chemotherapeutic drugs to reduce the side effects of the latter compounds.
Carcinogenesis 2007 Jun
PMID:Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. 1714 4

Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations in the ATM gene, is characterized by a high incidence of lymphoid malignancies, neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity, and genomic instability. Evidence has been accumulating that ATM-deficient cells are in a continuous state of oxidative stress. A variety of markers of oxidative stress were detected in AT patients as well as Atm-deficient mice, used as an animal model of AT. Since then, it has been proposed that oxidative stress contributes to the clinical phenotype of AT, especially carcinogenesis and neurodegeneration, and several animal studies were conducted to determine whether exogenous antioxidants mitigate the symptoms of AT. Tempol, EUK-189, and N-acetyl cysteine have been tested as chemopreventive antioxidants in Atm-deficient mice. We review these findings, mainly focusing on the effect of N-acetyl cysteine, which is known as a safe and efficient drug and nutritional supplement.
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PMID:Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice. 1718 31

The JC virus (JCV) infects a large proportion of the population world wide and can cause progressive multifocal leucoencephalopathy in the context of immunodeficiency. Recent reports provide evidence that it may also be oncogenic. Here, JCV was examined by targeting its T-antigen in lung carcinomas (n=103) and normal lung tissues (n=18) by nested-PCR followed by Southern blot, real-time PCR, immunohistochemistry, in situ hybridization and in situ PCR. Additionally, expression of Ki-67, caspase-3, beta-catenin, p53, and Rb was analysed by immunohistochemistry on tissue microarrays of lung carcinomas. Copy numbers of JCV were compared with clinicopathological features. Normal lung tissue was positive significantly less frequently, and contained a lower copy number of JCV than lung carcinomas (p<0.05), and copies were lower in lung adenocarcinomas than in squamous, small or large cell carcinomas (p<0.05). In situ PCR and immunolabelling revealed JCV positivity in the nuclei of lung carcinoma cells. The JCV copy number correlated closely with sex, and expression of Ki-67 and membrane beta-catenin (p<0.05), but not with age, tumour size, pleural invasion, lymph node metastasis, expression of caspase-3, cytoplasmic beta-catenin, p53 or Rb, prognosis, smoking or cancer family history (p>0.05). Age and UICC staging were independent prognostic factors for lung carcinoma patients. These data suggest that JCV may be involved in lung carcinogenesis, especially in tumour types other than adenocarcinoma. Lung carcinomas with higher JCV copy numbers display high proliferation and down-regulation of cell adhesion mediated by membrane beta-catenin.
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PMID:Oncogenic role of JC virus in lung cancer. 1753 44

Malignant uterine tumors are responsible for up to 9% of all new cancer cases and for 4.5% of all cancer related deaths in women. The three important uterine cancers are endometrial cancers, uterine sarcomas and cervical cancers. Endometrial cancers are typically found in elderly women and are > 70% hormone sensitive (type I), type II is often less differentiated and not hormone sensitive. Diagnosis can be achieved by vaginal ultrasound and by histology after hysteroscopy and curettage of the uterine cavity. Therapy of choice is the stage related radical hysterectomy (incl. lymphnode dissection). Postoperatively and at progressive stages endocrine and radiation therapies can be useful. Chemotherapy is only useful in not hormone sensitive and in progressive tumors. Uterine sarcomas are a rare and heterogeneous group of tumors. Therefore no clinical guidelines are available for this entity. These often aggressive tumors are hardly responding to systemic and radiation therapy. Therefore radical tumor surgery plays the main therapeutic role. Cervical carcinomas are usually growing on an underlying chronic infection with oncogenic HPV subtypes. Important co-factors for carcinogenesis are tobacco smoking, an immunodeficiency and chronic genital infections of other causes. Cervical carcinomas and their precursor lesions are easily accessible for screening tests. Many tumors are detected in early tumor stages. Preoperatively diagnostic procedures are performed to examine local and distant tumor growth. In early stages a radical hysterectomy (incl. pelvine (+paraaortal) lymphonodectomy) and in rare cases an uterus preserving surgery should be performed. Alternatively a primary radiochemotherapy can be applied. Patients with tumors in stages > or = FIGO IIb receive a primary combined radiochemotherapy.
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PMID:[Malignant tumors of the uterus]. 1794 55

The first consistent observations that viruses could be associated with some types of cancer where made almost a century ago. Since then researchers have spent a great deal of effort to address the infectious origins of human cancer. As a result of these studies, a strong link between some viral agents and several human cancers has been established. Some viruses as the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-cell lymphotropic virus type I (HTLV-I), immunodeficiency virus type I (HIV-I) and several human papillomavirus types (including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66) have been classified as group 1 carcinogens by the International Agency for Research in Cancer (IARC). Infection by these viruses constitutes a heavy burden for human populations as it accounts for almost 15% of all human malignancies. Furthermore, many other viral agents have been classified as possibly carcinogenic to humans and others have been occasionally found in human tumors suggesting that this figure may be an underestimation of virus involvement in the etiology of human cancer. Therefore, viral infection appears as one of the main preventable cancer risk factors. We summarize the current state of knowledge concerning virus-induced/associated cancers and discuss its significance in the context of human carcinogenesis. Prevention and control of infection by these agents could dramatically reduce the incidence of some prevalent cancers and, consequently, have a great impact on public health.
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PMID:Viral origins of human cancer. 1797 5

Information from a preceding lipid study contributed to the pathobiological assessment of laryngeal squamous cell carcinoma (LSCC). Lipid-driven signaling pathways are responsible for laryngeal carcinogenesis and immunodeficiency. The construction of fatty acid (FA) profiles for LSCC allowed the identification of FA role players. The integration of lipid and clinicomolecular information encountered in the literature, in turn, allowed the identification of biological prognostic markers to distinguish between early (less aggressive) and advanced (more aggressive) LSCCs. High arachidonic acid (AA) and cyclooxygenase (COX-2) activities are criteria for less aggressive growth, whilst low AA and COX-2 activities occur during more aggressive growth. Excessive tobacco use and environmental smoke or human papillomavirus (HPV) infection and alcohol abuse can, respectively, elicit cumulative oxidative stress and an oxidative burst or interfere with signaling pathways during essential fatty acid (EFA) metabolism, all factors and events which may cause LSCC. Research revealed that enhanced COX-2 activity and Bcl-2 expression prevent apoptosis and, hence, LSCCs become resistant to radiotherapy. It was also observed that recurrent laryngeal cancers become more aggressive after radiotherapy failure. It is predicted that manipulation of AA activity and consequently a cascade of downstream factors that include COX-2 and Bcl-2 expression responsible for LSCC may have therapeutic potential to improve radiotherapy outcome during early LSCC. Adjuvant FA therapy to improve early LSCC management by counteracting radiotherapy failure and unwanted complications for further management is proposed. FA therapeutic strategies before and during radiotherapeutic courses need to be evaluated.
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PMID:Rationale for adjuvant fatty acid therapy to prevent radiotherapy failure and tumor recurrence during early laryngeal squamous cell carcinoma. 1805 75


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