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 is a generic term for a variant manifestation of life caused by genetic mutations of somatic cells. It is not only carcinogenesis which is basically a genetic phenomenon, but also tumor progression which can be influenced by various genetic factors. A group of tumors is known to be inherited in a Mendelian fashion. In addition a great number of single gene disorders is associated with the development of maligne tumors. The further study of these diseases will allow new insights into the fundamental mechanisms leading to clinical cancer. In this respect a series of immunodeficiency diseases is of particular interest. Several organ tumors which seem to occur more frequently in relatives of tumor patients are of practical importance. A more sophisticated classification of these tumors may illuminate their genetic behavior. The geneticist cannot only define groups of individuals with a high cancer risk, but he can identify genetic, e.g. chromosomal, aberrations of cancerous cells which enables him the early detection of neoplasia.
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PMID:[Early diagnosis of neoplasms]. 72 76

p53 is a tumor suppressor gene that commonly undergoes mutations in human tumors, including lymphomas. Because p53 mutations are not restricted to a single locus, immunohistochemistry is useful to detect p53 expression and correlate this finding with lymphoma phenotype. Cryostat sections from 125 cases of lymphoma were analyzed for p53 expression using three different monoclonal antibodies (pAb 421, 1801, 240) which react with human cellular p53 and a common conformational epitope on mutant p53. A control antibody (pAb 246) reacts only with wild type p53 of murine origin and was negative in all cases. Tissue from 29 cases of lymphoid hyperplasia, including six from human immunodeficiency virus-positive (HIV+) patients, were negative for p53. p53 was predominantly localized in nuclei of high-grade lymphomas, including 14 of 46 cases of B cell immunoblastic lymphomas and two of five T cell immunoblastic lymphomas. p53 expression was relatively common in lymphomas from HIV+ patients, and unusual in intermediate and low-grade lymphomas of follicular center cell type. Low-grade lymphoma of small lymphocytic type disclosed p53+ large cells (paraimmunoblasts) that may play a role in tumor progression in this lymphoma subtype. p53 was also strongly expressed in the nuclei of Reed Sternberg cells from 19 of 37 cases of Hodgkin's disease, including six cases of mixed cellularity, and 13 cases of nodular sclerosing type. Immunohistochemical staining is a rapid method to identify p53 expression in lymphomas.
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PMID:Immunohistochemical analysis of p53 expression in malignant lymphomas. 146 98

During a 2-year period 5 men positive for the human immunodeficiency virus (HIV) presented with 6 testis tumors among a total of 3,015 men seen at our hospital acquired immunodeficiency syndrome (AIDS) clinic. This testis tumor incidence of 0.2% is 57 times that of the United States average of 3.5 cases per 100,000 men. Two patients were only HIV positive and 3 others already had AIDS-related complex for 2 to 15 months at the time of tumor diagnosis. Tumor histology was mixed germ cell tumor in 4 patients, pure seminoma in 1 and Burkitt's lymphoma in 1. Patients underwent routine staging evaluations. Three patients had low stage mixed germ cell tumor (clinical stage 1 or 2A) and underwent retroperitoneal lymphadenectomy, which revealed pathological stage 1 or 2A disease in 1 and 2, respectively. These patients did not receive adjuvant chemotherapy. Two patients had advanced mixed germ cell tumor (clinical stage 2C) or Burkitt's lymphoma (clinical stage 4) and received combination chemotherapy from the onset. Outcome was evaluated with regard to progression of HIV disease and tumor status. The 2 patients who were only HIV positive remained so for 9 and 48 months. The 3 patients with AIDS-related complex had progression to AIDS within 1 to 9 months and 2 of these patients died 1 1/2 and 7 months after tumor diagnosis. All 3 patients with resected low stage disease had tumor recurrence within 1 to 9 months and were begun on platinum-based combination chemotherapy. The risk of false low clinical staging and early tumor progression may be higher in HIV positive men than in other testis tumor patients. Patient ability to tolerate chemotherapy and to obtain a satisfactory tumor response appeared to be primarily related to lack of progression of HIV disease to frank AIDS.
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PMID:Testicular tumors in men with human immunodeficiency virus. 155 81

Levels of a 90,000 daltons monoclonal antibody-defined tumor-associated antigen, termed 90K, were measured in the serum from 649 patients with various types of cancer and 1215 patients infected by the human immunodeficiency virus (HIV). Significantly increased 90K serum levels (12.1 +/- 0.5 U/ml) were found in cancer patients with respect to healthy controls (5.7 +/- 0.3 U/ml), with the highest levels in neoplasms of the breast, lung and gastrointestinal tract. In 355 patients with breast cancer, the elevation of serum 90K levels was more pronounced at advanced stages of disease. Mean levels of 90K for 1215 HIV-infected subjects (21.2 +/- 0.8 U/ml) were significantly higher than controls and cancer patients, and the levels progressively increased with disease worsening from asymptomatic infection to full blown AIDS. These data suggest that 90K is not merely a tumor-associated antigen and lead us to postulate it to be a signalling molecule whose production might be related to the immune deficit caused by pathogenetic events such as neoplastic progression and virus infection.
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PMID:Elevated serum levels of a 90,000 daltons tumor-associated antigen in cancer and in infection by human immunodeficiency virus (HIV). 806 21

The authors report five patients with primary intracerebral non-Hodgkin's lymphoma who were treated with several cycles of intra-arterial injection of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) at doses of 80 to 100 mg/m2/injection at several monthly intervals. There was no simultaneous use of steroids, and no patients had concomitant immunosuppression; no patient was human immunodeficiency virus positive. This therapy was initially used in four patients with advanced recurrent lymphoma. These patients experienced tumor progression despite our institutional standard therapy comprising cranial irradiation followed by repeated courses of systemic multi-agent chemotherapy (cyclophosphamide, vincristine, adriamycin, and prednisolone) more than 3 months previously. Based upon brain computed tomography scans and clinical neurologic examinations, three of the four cases showed partial responses ranging from 10 to 12 months in duration, whereas the other patient remained stable without worsening for 8 months. A fifth case was particularly noteworthy; this patient had no prior therapy and intra-arterial chemotherapy alone induced an 18-month, disease-free remission. No significant therapy-related complications nor neurotoxicity were seen. These results suggest that intra-arterial administration of ACNU may be a potential candidate for intracerebral lymphoma therapy.
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PMID:Chemotherapeutic effects of intra-arterial administration of ACNU in primary intracerebral non-Hodgkin's lymphoma. 821 54

The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antiretroviral therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71+/-51 weeks) with a mean of 22.8+/-18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456+/-364 mg/m(2) (120-1040 mg/m(2)). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.
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PMID:Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin. 1131 76

Immunodeficient patients have an increased incidence of neoplasms, whether the immunodeficiency is due to genetic disorder, the acquired immunodeficiency syndrome (AIDS), or immunosuppressive therapy. Leiomyosarcoma (LMS) is a rare neoplasm, even if its incidence has increased because of AIDS. Less than fifteen cases were described after organ transplantation. An intracranial localization is exceptional (five cases in the literature) and was never described after organ transplantation, to our knowledge. Our present report focuses on a 45-year-old immunocompromised patient, who received immunosuppressive therapy for renal transplantation. He suffered from atypical peri-orbital headaches six months after transplantation and a mass involving the cavernous sinus was identified. Surgical biopsy was performed. Histologic examination revealed a LMS. Epstein-Barr virus was identified by quantitative polymerase chain reaction in the LMS. Immunosuppression was reduced, the patient received adriamycin and protontherapy was realized. He died two years after the transplantation because of tumor progression and kidney failure.
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PMID:[Primary leiomyosarcoma of the cavernous sinus associated with Epstein-Barr virus in a kidney graft]. 1471 28

The anatomic distribution and rate of progression vary significantly between acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) and classic KS. The reasons are unclear, but cyclin D1 overexpression is associated with tumor progression in other malignancies. Cyclin D has an important regulatory role in the progression of cell cycle at the G1-S phase due to its effect in phosphorylating the retinoblastoma gene product. Forty-one paraffin-embedded surgical specimens (31 AIDS-related, 10 classic) were examined using streptavidin-biotin-peroxidase immunohistochemistry with monoclonal antibody to cyclin D1. A scoring system based on the intensity and extent of staining was used. The correlations among cyclin D1 expression and clinicopathologic parameters were statistically analyzed. Cyclin D1 overexpression was found in 29% (12/41) of all KS cases. There was a strong correlation between cyclin D1 overexpression and pathologic stage (0% in patch stage, 13% in plaque stage, 50% in nodular stage; P = 0.0017). Classic KS lesions had a higher incidence of cyclin D1 overexpression than AIDS-related lesions (70% vs 16%, P = 0.001). Cyclin D1 overexpression was detected in 78% of the classic nodular lesions and 31% of the AIDS-related nodular lesions (P = 0.03). On multivariate analysis, negative human immunodeficiency virus status (P = 0.001) and nodular lesions (P = 0.007) were strong predictors of cyclin D1 overexpression. Age, gender, recurrence of the tumor, multiplicity, and site of the lesions hold no statistically significant association with cyclin D1 expression on multivariate analysis. In summary, cyclin D1 overexpression was more prevalent in classic lesions and more advanced nodular stage. These findings raise the possibility of a different pathogenetic mechanism in the progression of AIDS-related KS and classic KS.
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PMID:Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma. 1516 15

The proliferative capacity of mammalian cells is regulated by telomerase, an enzyme uniquely specialised for telomeric DNA synthesis. The critical role of telomerase activation in tumor progression and maintenance has been well established in studies of cancer and of oncogenic transformation in cell culture. Experimental data suggest that telomerase activation has an important role in normal somatic cells, and that failure to activate sufficient telomerase also promotes disease. Evidence regarding the role of telomerase in the pathogenesis of several viruses including human immunodeficiency virus has led to an increased interest in the role of telomerase activity in other virus infections. In this research we evaluated the telomerase modulating activity of Bovine herpesvirus 1 (BHV-1) in MDBK cells. MDBK cells were infected at different multiplicity of infection with BHV-1 Cooper strain and telomerase activity at different times post-infection was measured by the TRAP assay. Our data indicate that BHV-1 significantly up-regulates telomerase activity at 3 and 6h post-infection decreasing after the 24h post-infection. Our data, showed that the effect was mediated by an immediate-early or early viral gene, and use of the protein translation inhibitor cycloheximide confirmed that an immediate early gene is primarily responsible.
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PMID:Bovine herpesvirus type 1 (BHV-1) up-regulates telomerase activity in MDBK cells. 1633 Jan 62

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.
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PMID:A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer. 1635 94


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