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)

Narcotic opioid compounds are among the most widely prescribed drug interventions for individuals suffering pain. Among the unwarranted side effects of respiratory depression, constipation, and physical dependence are the immunosuppressive qualities, particularly those which affect cell-mediated immunity. The immunosuppressive characteristics of opioid narcotics (e.g., morphine) have recently come into focus with the advent of acquired immune deficiency syndrome (AIDS) and the putative causative agent, human immunodeficiency virus type 1 (HIV-1). Specifically, a vast reservoir of HIV-1-infected individuals exists among drug abusers. Moreover, experimental evidence would suggest narcotic opioids may increase viral load in infected individuals by modifying the cellular machinery of activated leukocytes. Likewise, investigators have shown that opioids modify tumor growth and development. In this review, a comparison between endogenous opioid peptides and exogenous opiates on cell-mediated immunity and its relationship to viral infection and tumors is described.
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PMID:Exogenous and endogenous opioids as biological response modifiers. 865 91

A 63-year-old Japanese male with a four-year history of asymptomatic hypogamma-globulinemia is presented. On admission, he had a mild bone marrow plasmacytosis at about 10% of the total nucleated cells, but had no anemia, no paraproteins nor bone lesions. Flow cytometric analysis showed a predominant proliferation of kappa chain-positive cells in the bone marrow and peripheral blood, and an increase in the proportion of natural killer cells in the peripheral blood. Furthermore, coexistent meningioma and transitional cell carcinoma of the bladder were subsequently found 9- and 15-months after the admission, respectively. We considered that a myeloma-induced, possible latent immunodeficiency may have allowed the additional tumor growth, and that this process may have been controlled by the cytotoxic subset of immune effector cells.
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PMID:Asymptomatic multiple myeloma with concomitant neoplasms of two different origins. 898 71

The acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) is a potent and selective antiretroviral agent which is currently evaluated in its oral prodrug form, bis(POM)PMEA (adefovir dipivoxil), in phase II and III clinical trials in human hepatitis B virus (HBV)- and human immunodeficiency virus (HIV)-infected individuals, respectively. We have now found that PMEA is also a potent inhibitor of growth of the highly aggressive choriocarcinoma tumor arising from rat choriocarcinoma RCHO cells grafted under the kidney capsule of syngeneic WKA/H rats. In untreated rats, massive invasive RCHO tumors, covering the whole surface of the kidney and resulting in a marked enlargement of the kidney, were observed at day 10 after tumor cell grafting. Daily treatment with PMEA at 25 mg/kg/day afforded a marked reduction in tumor size (i.e., smaller tumors and slight, if any, enlargement of the kidney). Increasing the PMEA dose to 50, 100 or 250 mg/kglday resulted in a gradual increase of the antitumor effect of the compound. At the highest dose tested, i.e., 250 mg/kg/day, PMEA completely suppressed tumor growth. The antitumor activity of PMEA persisted for at least 10 days after termination of drug treatment. In addition, delayed treatment with PMEA at a dose of 200 mg/kg/day, started at a time point where choriocarcinoma tumors had already developed, stopped further growth and even induced regression of the tumors. PMPA, a closely related structural analogue of PMEA, failed to inhibit choriocarcinoma tumor growth. This observation points to the specificity of PMEA as an antitumor agent. In view of our findings, the therapeutic potential of PMEA for the treatment of neoplastic diseases appears to merit further investigation.
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PMID:Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine in choriocarcinoma-bearing rats. 959 Jan 39

Epstein-Barr virus (EBV) has been detected in the large majority of HIV-related primary central nervous system lymphomas (PCNSL) suggesting a pathogenetic role of the virus. Unlike HIV-related PCNSL, conflicting data exist with regard to the presence of EBV in non immunodeficiency-related (sporadic) PCNSL. For this reason, a population based material of 41 sporadic PCNSL was analysed for the presence of EBV genome (EBER, BHLF) using RNA in situ hybridisation (RISH). Furthermore, the expression of the gene products of the bcl-2 oncogene and the p53 tumor suppressor gene and the tumor growth fraction reactive with the monoclonal antibody Ki-67 have been evaluated. All cases but two were EBV genome negative. In the two positive cases less than 5% of tumor cells showed EBER positivity. In contrast, more than 75% of cells morphologically belonging to the tumor-cell population stained positively for EBER in two cases of HIV related PCNSL. Immunostaining for the bcl-2 oncoprotein was positive in 28 (72%) of 39 cases examined. In most cases more than 75% of tumor cells showed cytoplasmic expression. Of 37 cases investigated for p53 expression, 21 (57%) stained positively. However, in the large majority of positive cases less than 10% of the neoplastic cells stained. The percentage of Ki-67 positive cells ranged between 10% and 80% with a mean of 50%. The expression of the p53 and bcl-2 oncoproteins and the growth fraction did not have any prognostic impact. We conclude that the EBV genome is rarely detected in sporadic PCNSL, indicating that a pathogenetic role of EBV is unlikely. Like extracerebral B-cell lymphomas a large fraction of PCNSL expresses the p53 and bcl-2 oncoproteins, a feature, however, which does not seem to have prognostic implications.
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PMID:Primary central nervous system lymphomas in immunocompetent individuals: histology, Epstein-Barr virus genome, Ki-67 proliferation index, p53 and bcl-2 gene expression. 966 83

A cell line (ISO-HAS) has been established from tumor tissue of a human hemangiosarcoma arising on the scalp by the use of conditioned medium from a murine-phenotypic angiosarcoma cell line (ISOS-1). Cells have been cultured for more than 2 years with up to 100 passages. The cells retained endothelial-cell properties, such as a characteristic cobblestone appearance at confluency, contact-inhibited growth, active uptake of acetylated low-density lipoprotein labeled with 1,1-dioctadecyl 1,3,3,3,3-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) and CD31 expression. However, they were weakly positive for von-Willebrand-factor (vWf) antigen and for binding of Ulex europaeus agglutinin-I (UEA-I) lectin, and lacked tube-formation activity. These findings indicate that ISO-HAS is a poorly differentiated endothelial cell line. ISO-HAS cells showed accumulation of p53 protein in the nuclei, and a new-typed p53-gene point mutation was found in exon 7 at codon 240. When inoculated s.c. into severe-combined-immunodeficiency (SCID) mice, the cells showed solid-tumor growth that caused death. These properties suggest that ISO-HAS is a malignant endothelial cell line with high tumorigenicity.
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PMID:Establishment of a human hemangiosarcoma cell line (ISO-HAS). 1018 35

Patients with advanced cancer often develop immunodeficiency which may be associated with granulocytosis. The granulocytes have the potential to deplete cytotoxic T cells, resulting in accelerated tumor growth and metastasis. To study the elimination of excess granulocytes using granulocyte apheresis in patients with elevated granulocyte to lymphocyte ratios, 2 patients with recurrent metastatic tumors, were selected. Granulocyte apheresis was performed by extracorporeal vein-to-vein circulation with the G-1 granulocyte and monocyte/macrophage apheresis column filled with cellulose acetate beads, each 2 mm in diameter to adsorb granulocytes and monocytes/macrophages. The patients received 1 or 2 apheresis of 30 to 50 min duration per week, at a flow rate of 30-50 ml/min, with 15 sessions constituting one therapeutic course. Apheresis markedly reduced tumor size and prolonged patient survival time without causing any serious adverse events. The results of the present study suggest that granulocyte and monocyte/macrophage apheresis may be beneficial in patients with metastasizing tumors.
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PMID:Granulocyte apheresis as a possible new approach in cancer therapy: A pilot study involving two cases. 1046 94

Kaposi's sarcoma (KS) is the most common neoplasm associated with human immunodeficiency virus-1 (HIV-1) infection. KS involves the skin and mucous membranes as well as other organs and can lead to tumor-associated edema and ulcerations. Despite therapy with highly active antiviral agents, most patients with HIV-1-related KS eventually develop disseminated disease. In the treatment of KS, a strong rationale exists for the use of agents that inhibit vascular endothelial growth factor (VEGF). Angiogenesis appears to be an important feature of this disease, and recent experimental studies have demonstrated the role of VEGF and its receptors in the pathogenesis of KS. Thus, therapeutic agents that target the VEGF pathway may be an effective strategy in reducing the tumor growth and edema associated with KS. Phase I study results with SU5416, a synthetic low molecular-weight inhibitor of the VEGF-Flk-1/KDR receptor tyrosine kinase, demonstrate that this agent is well tolerated. Preliminary results show that in a majority of patients with autoimmune deficiency syndrome (AIDS)-related disease, SU5416 clearly has biological activity (it flattens, shrinks, or dissolves lesions and reduces or resolves edema) or stabilizes the disease. Angiogenesis inhibition with SU5416 is a promising therapeutic approach in treating patients with KS, and further clinical evaluation is currently under way.
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PMID:The role of vascular endothelial growth factor (VEGF) in AIDS-related Kaposi's sarcoma. 1080 88

Although dendritic cell (DC)-based cancer-specific immunotherapy is a potent strategy for various types of carcinomas, few clinical studies have yielded optimal antitumor effects. Systemic immunodeficiency is observed in patients with advanced malignant disease. In this study, we explored the ability to induce antitumor immunity of the cultured monocyte-derived DCs from hosts with advanced malignant disease, using a mouse model. We found remarkable dysfunction of DCs from mice with advanced cancer, which exhibited T helper (Th)2-dominant immunity, and subsequent reduced antitumor immune response. On the other hand, we found dramatic restoration of the ability of DCs to induce optimal antitumor immune responses after systemic administration of streptococcal preparation OK-432 to the tumor-bearing mice, which induced Th1-dominant immunity. In therapeutic experiments, intratumoral injections of immature DCs from the OK-432-treated mice, designated OK-DCs, enhanced inhibition of tumor growth compared with injections of immature DCs from mice with advanced malignancies, designated T-DCs (P < 0.05), leading to significant prolongation in overall survival (P < 0.05). In analysis of cell surface antigens, antigen-presenting capability and interleukin 12 production, we showed functional skewing in T-DCs and significant restorations in OK-DCs. More CD8+ tumor-infiltrating lymphocytes were detected in the mice treated with OK-DCs; furthermore, CTL assays showed that intratumoral injection of OK-DCs induced tumor-specific immune response to spleen as great as those of N-DCs. These results suggested that Th1-dominant immunity might play a crucial role in the differentiation of DCs, and OK-432 might be useful for inducing optimal antitumor effects in DC-based immunotherapy in tumor-bearing hosts.
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PMID:Effective strategy of dendritic cell-based immunotherapy for advanced tumor-bearing hosts: the critical role of Th1-dominant immunity. 1249 11

Elimination of about 30% lymphocyte population was observed in female Balb/c mice on day 11 after transplantation of Ehrlich carcinoma in comparison with animals without tumor. It was hypothesized that the eliminated population can block the tumor growth. Studies of the temporal and quantitative parameters of lymphocyte elimination with consideration for tumor size are considered to be perspective. The described model can be used for studies of immunodeficiency in animals with tumors.
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PMID:Partial elimination of lymphocytes in mice with Ehrlich carcinoma. 1280 27

p16 is an important regulator of the cell cycle at the G(1) phase. Frequent aberration of p16 in nasopharyngeal carcinoma (NPC) suggests a role for this tumor suppressor gene in disease development. p16 gene transfer has been demonstrated to be effective in various human cancer models, including breast, lung, and prostate, causing cell cycle arrest, apoptosis, and tumor growth delay. We investigated the potential of adenoviral-mediated p16 therapy, in combination with ionizing radiation (RT), in two distinct NPC models. Two deltaE1 adenoviral vectors were employed: one carrying the human p16 gene (adv.p16), and the other a beta-galactosidase reporter gene (adv.beta-gal), both driven by the cytomegalovirus (CMV) promoter. Two NPC cell lines with differential endogenous p16 expression, CNE-1 (low) and CNE-2Z (high), were evaluated for protein expression, cytotoxicity, cell cycle analysis, apoptosis, and senescence. The CNE-1 cells were exquisitely sensitive to adv.p16, with 0.1% survival level after gene therapy [25 plaque-forming unit (pfu)/cell], which further decreased to 0.01% with the addition of RT (2 Gy). This reduction in survival was effected through necrosis, G1 arrest, and senescence. In contrast, CNE-2Z cells were resistant to adv.p16 gene transfer, with 75% surviving at an equivalent viral dose. This differential sensitivity was recapitulated in vivo in that adv.p16-treated CNE-1 cells formed no tumors in severe-combined-immunodeficiency (SCID) mice, followed for over 100 days. In contrast, tumor formation was detected 40 days after implantation of adv.p16-treated CNE-2Z cells. In conclusion, adv.p16 gene transfer appears to be highly effective against NPC that lack functional p16, which is the situation in the majority of NPC patients.
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PMID:p16 gene therapy: a potentially efficacious modality for nasopharyngeal carcinoma. 1457 61


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