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)

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in men and women in the United States. It affects nearly as many people each year as does the human immunodeficiency virus and has a much worse outcome. This article reviews the progress in treatment of this disease since 1975, outlines the current clinical and research challenges in the field, and suggests a plan of action to address these challenges. The world literature in the field since 1975 was reviewed, and the pancreatic cancer Progress Report Group of the National Cancer Institute (NCI) is reviewed and presented. Some progress has been made in understanding and treating pancreatic cancer since 1975. Much remains to be done. The lack of progress in the field can largely be attributed to the lack of importance and subsequent lack of research dollars attributed to it by the NCI. The NCI is addressing this issue by proposing to fund Specialized programs of research excellence grants in pancreatic cancer. In addition, other mechanisms exist within the NCI to allow for additional funding of pancreatic cancer. Using the tremendous progress made in the field of human immunodeficiency virus research as an example, it is hoped that similar improvements can be made in the field of pancreatic cancer if substantial and sustained efforts are made.
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PMID:The challenge of pancreatic cancer. 1467 61

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

Dendritic cells (DCs) play a pivotal role in T cell-mediated immunity and have been shown to induce strong antitumor immune responses in vitro and in vivo. Various approaches utilizing different vaccine cell formats, cell numbers, vaccination schedule, site of vaccination and maturation stages of DCs were investigated worldwide. While clinical trials have demonstrated the safety of such strategies, the clinical outcome was less than expected in most cases. This is due to in part host immunodeficiency imposed by tumors and immunoediting of tumor cells. To overcome these obstacles, new approaches to improve DC-mediated immunotherapeutic strategies are under investigation. First, functional enhancement of monocyte-derived DCs can be generated with using flt3-ligand (FL). Second, diverse antigenic determinants from heat shock-treated tumor cells may improve the immunogenicity of DC-based vaccines. Third, inclusion of ex vivo expanded NK/NKT cells in DC-based vaccines could be beneficial since the bidirectional interaction of these two cell types are known to enhance NK cell effector function and to induce DC maturation. Application of these approaches may induce a broadened antitumor immune response and thereby promote the elimination of tumor antigen-negative variant clones that had escaped immunosurveillance or undergone immunoediting. We are currently examining the feasibility of these immunotherapeutic approaches using a murine pancreatic cancer model system.
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PMID:Strategies to improve dendritic cell-based immunotherapy against cancer. 1525 50

Cell-mediated immunodeficiency, with Total and T lymphocytes count decrease, is well established in cancer patients and it predicts a poor prognosis and poor survival rates. Furthermore, major surgery induces a transient immunodeficiency, too. Nevertheless, cell-mediated immunity in pancreatic cancer, which has a very poor prognosis, has not been completely outlined. Aim of this study is to evaluate the cell-mediated IL-2 dependent immune status in operable pancreatic cancer patients and to compare it with other gastrointestinal tumors. One hundred and twenty-one cancer patients (22 pancreatic, 48 gastric and 51 colorectal), with a median age of 66 years (range 42-83), 55 males and 66 females, were enrolled. Total lymphocyte count and lymphocytes subset (T helper count - CD4+) were assessed preoperatively and on the 14th and 50th postoperative day. Results obtained were compared between the groups and related to nodal involvement (N0 versus N+). Colorectal and gastric cancer patients showed quantitative lymphocyte deficiency at baseline in 29% and 41% of cases, respectively. Fourteen days after surgery values below normal range were found in 44% and 54% (Total) and 53% and 67% (T helper), respectively. Recovery of postoperative surgery-related lymphocytopenia occurred late only in patients with normal count at baseline. According to regional nodal involvement (pN0/N+) T helper deficiency was significantly more frequent in patients with nodal involvement than in patients without. In pancreatic cancer, percentage of immunodepressed patients at baseline was higher compared to the other two groups (71%). Lymphocyte count was significantly different between pancreatic and gastric/colorectal cancer, reaching a statistical significance at baseline and on the 14th and 50th postoperative day. No differences of T helper deficiency were noted according to nodal involvement (N0 versus N+) neither at baseline nor in the postoperative period. In conclusion, the degree of immunosuppression varies among different tumor types: since initial stages of disease, immunodepression was significantly greater in pancreatic cancer which should be considered always a systemic disease even in early stages and indipendently from the nodal involvement and from tumor load.
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PMID:Immunodeficiency in different histotypes of radically operable gastrointestinal cancers. 1535 2

Suicide gene therapy using the herpes simplex virus thymidine kinase (TK) gene in combination with ganciclovir (GCV) has been shown to produce therapeutic, but limited, efficacy because of poor gene transfer efficiency and reduced bystander effect. Here we report that fusion of TK to an eight-amino acid peptide from the basic domain of the human immunodeficiency virus (HIV) Tat protein significantly increases the cytotoxic efficacy of the TK/GCV system in pancreatic cancer cells. We demonstrate that Tat8-TK protein is released from the intracellular compartment of Tat8-TK-expressing cells to the extracellular medium after GCV treatment. Interestingly, we show that this conditioned medium is then able to mediate cytotoxicity of wildtype cultures, suggesting the internalization of the Tat8-TK protein. Moreover, a strong antitumoral effect of Tat8-TK/GCV treatment could be achieved by two different in vivo approaches. Tumors injected with NIH 3T3/Tat8-TK cells attached to microcarriers (MC+Tat8-TK) and treated with GCV led to a 35.6% reduction in the initial tumor volume and to 50% tumor eradication. Furthermore, electrogene transfer of TK or Tat8-TK followed by administration of high doses of GCV led to an overall statistically significant reduction in tumor growth. However, the reduction in initial tumor volume was statistically significant only for the Tat8-TK group (59.5% reduction). Moreover, in this group 50% complete tumor eradication was achieved. When moderate doses of GCV were administered, the overall reduction in tumor growth was statistically significant only in the Tat8-TK group. Therefore, our results suggest that fusion of TK to the Tat8 peptide enhances TK/GCV suicide gene therapy.
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PMID:Tat8-TK/GCV suicide gene therapy induces pancreatic tumor regression in vivo. 1639 Feb 69

Good syndrome, characterized by both thymoma and hypogammaglobulinemia, is a rare immunodeficient disorder. We experienced a case of Good syndrome accompanied by myasthenia gravis (MG). A 58-year-old man was admitted to our hospital because of muscle weakness and fatigability. Based on the presence of anti-acetylcholine receptor (AChR) antibody and thymoma, he was diagnosed as having MG. Peripheral blood lymphocyte count was normal, but gammaglobulin levels were markedly decreased (IgG 283 mg/dl, IgA 17 mg/dl, IgM 1 mg/dl). Clinical remission of MG was achieved by thymectomy followed by high-dose corticosteroids. Despite monthly intravenous immunoglobulin supplementation, he suffered from repeated respiratory tract infections and candidiasis. Body CT revealed adrenal tumor and pancreatic cancer with liver metastasis, and he died of bacterial pneumonia. Immunological evaluations showed complete lack of CD19+ B cell in the peripheral blood and responses of peripheral blood mononuclear cells to mitogens. Peripheral blood T cells responded to a suboptimal concentration of a recombinant AChR fragment: this pattern of AChR-induced T cell response was typical of MG patients. We failed to detect IgG autoantibodies reactive with B cells in his serum. Patients with Good syndrome represent imbalance of immune responses, leading to both immunodeficiency and autoimmunity.
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PMID:[A case of Good syndrome accompanied by myasthenia gravis: immunological evaluations]. 1665 8

Few effective treatments for pancreatic cancer exist, especially for patients with advanced disease. Gene therapy alone, or combined with current treatments, offers an alternative approach. Here we examined the potential of primate and nonprimate lentivectors to mediate gene delivery to this cancer type. VSV-G pseudotyped lentivectors based on human immunodeficiency type-1 virus (HIV-1) and equine infectious anemia virus (EIAV), containing the enhanced green fluorescent protein (EGFP) reporter gene were prepared and characterized for titer and RNA content. Vector-mediated gene delivery was examined in five pancreatic cancer cell lines in vitro, and in MiaPaCa-2 cells as well as in five human primary patient biopsies xenografted subcutaneously in nude mice. While individual cell lines showed differential sensitivities to transduction with lentivectors, all cell lines were successfully transduced with both vector types. Similarly, both vectors transduced MiaPaCa-2 and all of the human primary patient xenografts. We observed 6-29% transduction with HIV-based vectors (n=3 xenografts) and 1.8-30% with EIAV-based vectors (n=4 xenografts). Long-term EIAV-mediated gene expression was recorded in cell lines for up to 6 months. We conclude that these vectors have potential as mediators of clinical gene therapy for pancreatic cancer treatment. Moreover, they are useful laboratory research tools for pancreatic cancer research.
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PMID:Both HIV- and EIAV-based lentiviral vectors mediate gene delivery to pancreatic cancer cells and human pancreatic primary patient xenografts. 1757 Oct 71

Pancreatic cancer (PC) remains a life-threatening disease. Efficient therapeutic gene delivery to PC-derived cells continues to present challenges. We used self-inactivated lentiviral vectors to transduce PC-derived cells in vitro and in vivo. We showed that lentiviral vectors transduce PC-derived cell lines with high efficiency (>90%), regardless of the differentiation state of the cell. Next, we transferred human interferon beta (hIFN-beta) gene. Expression of hIFN-beta in PC cells using lentiviral vectors resulted in the inhibition of cell proliferation and the induction of cell death by apoptosis. In vivo, lentiviral administration of hIFN-beta prevented PC tumor progression for up to 15 days following gene therapy, and induced tumor regression/stabilization in 50% of the mice treated. Again, hIFN-beta expression resulted in cancer cell proliferation inhibition and apoptosis induction. We provide evidence that human immunodeficiency virus (HIV)-1-based lentiviral vectors are very efficient for gene transfer in PC-derived cells in vitro and in vivo. As a consequence, delivery of hIFN-beta stopped PC tumor progression. Thus, our approach could be applied to the 85% of PC patients with a locally advanced disease.
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PMID:Using lentiviral vectors for efficient pancreatic cancer gene therapy. 1991 Oct 32

Feline leukemia virus (FeLV) is a gammaretrovirus that is a significant cause of neoplastic-related disorders affecting cats worldwide. Treatment options for FeLV are limited, associated with serious side effects, and can be cost-prohibitive. The development of drugs used to treat a related retrovirus, human immunodeficiency virus type 1 (HIV-1), has been rapid, leading to the approval of five drug classes. Although structural differences affect the susceptibility of gammaretroviruses to anti-HIV drugs, the similarities in mechanism of replication suggest that some anti-HIV-1 drugs may also inhibit FeLV. This study demonstrates the anti-FeLV activity of four drugs approved by the US FDA (Food and Drug Administration) at non-toxic concentrations. Of these, tenofovir and raltegravir are anti-HIV-1 drugs, while decitabine and gemcitabine are approved to treat myelodysplastic syndromes and pancreatic cancer, respectively, but also have anti-HIV-1 activity in cell culture. Our results indicate that these drugs may be useful for FeLV treatment and should be investigated for mechanism of action and suitability for veterinary use.
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PMID:Discovery of drugs that possess activity against feline leukemia virus. 2225 56

Pancreatic cancer affects 44,000 Americans and at least 250,000 individuals worldwide annually. The incidence is slowly increasing after a recent period of decline. Cases are predicted to increase globally because of increased longevity and the widespread adoption of cancer-causing behaviors, such as cigarette smoking, dietary indiscretion, and a global increase in diabetes. Well-known risk factors for pancreatic cancer are advancing age, tobacco smoking, obesity, certain inherited familial disorders, second-hand smoke exposure, chronic pancreatitis, and diabetes. Associations with human immunodeficiency virus, ABO blood group, hepatitis B virus, human immunodeficiency virus, and Helicobacter pylori have also been identified.
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PMID:Demographics and epidemiology of pancreatic cancer. 2318 33


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