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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus (Ad) DNA replication requires nuclear factor I (NFI), a cellular sequence-specific DNA binding protein which binds to the Ad DNA inverted terminal repeat (ITR). The NFI binding consensus sequence, TGGN6-7GCCAA, possibly includes the CCAAT-box which is often observed in regulatory elements of transcription. Adjacent to the NFI binding site on the Ad ITR is the binding site for nuclear factor III (NFIII), another cellular factor that stimulates Ad DNA replication in a cell-free system. Using gel retardation assay, we have examined the tissue specificity of these DNA binding activities in mouse. High NFI activity was detected in nuclear extracts from mouse liver, kidney, and spleen. Competition gel retardation assay with double-stranded oligonucleotides containing herpes simplex virus thymidine kinase (HSV-TK) gene or hsp70 gene CCAAT-box showed no effect on mouse NFI binding to its binding site. In the course of competitive DNA-binding assay, we detected a novel DNA binding protein in mouse kidney nuclear extracts, designated nuclear factor K (NFK). The NFK binding site is included in the NFIII binding site on the Ad ITR. NFK seems to be different from NFIII, in mode of binding to its binding site.
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PMID:Tissue-specific DNA binding of nuclear proteins that bind to the adenovirus inverted terminal repeat. 276 19

Human adenovirus type 5 enhances the thymidine kinase activity of KB cells but does not induce the enzyme in kinase-deficient HeLa (BU25) cells. Vaccinia induces thymidine kinase activity in both KB and HeLa (BU25) cells. Human adenovirus types 2, 4, 7, and 12 also fail to induce the enzyme in HeLa (BU25) cells. Vaccinia replicates equally well in the presence or absence of HATG (hypoxanthine-aminopterin-thymidine-glycine) in KB and HeLa (BU25) cells. Adenovirus type 5 replicates in KB and in HeLa (BU25) cells in the absence of HATG, and adenovirus type 5 replicates in kinase-positive KB cells in the presence of HATG. However, replication of adenovirus type 5 is grossly inhibited in HeLa (BU25) cells in the presence of HATG. These results suggest that human adenoviruses do not code for a new virus-specific thymidine kinase.
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PMID:Origin of thymidine kinase in adenovirus-infected human cell lines. 545 2

Biochemical events were investigated in the G1 to S phase progression induced in quiescent rodent cells by human adenovirus type 5 (Ad5) and by serum. Thymidine kinase activity increased after infection of cells with Ad5 or addition of 10% serum. These stimulations were additive. An early viral gene was responsible for induction by Ad5, but the early mutants ts36, ts37, and ts125 induced thymidine kinase at the permissive and nonpermissive temperatures. Several differences were found between cells stimulated by serum compared with Ad5. Induction of thymidine kinase was delayed in Ad5-infected cells, insensitive to 0.01 microgram/ml actinomycin D and relatively resistant to reduced Ca2+ compared with induction by serum. Ornithine decarboxylase was induced by serum, but not by Ad5, alpha-Methylornithine had little effect on the induction of thymidine kinase by Ad5, but reduced the induction of thymidine kinase by serum, suggesting that Ad5-induced entry into S phase is uncoupled from polyamine biosynthesis. Methylglyoxal bis(guanylhydrazone), however, prevented the induction of thymidine kinase by both serum and Ad5. Adenovirus infection appears to induce cellular DNA synthesis and thymidine kinase in G1-arrested cells by a mechanism different from serum, and bypasses events in the normal G1 to S phase progression.
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PMID:A biochemical investigation of the adenovirus-induced G1 to S phase progression: thymidine kinase, ornithine decarboxylase, and inhibitors of polyamine biosynthesis. 706 69

Adenovirus type 5 induces cellular DNA synthesis and thymidine kinase in quiescent rat cells but does not induce ornithine decarboxylase. We now show that unlike serum, adenovirus type 5 fails to induce S-adenosylmethionine decarboxylase or polyamine accumulation. The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis. Thus, induction of cellular thymidine kinase and DNA replication by adenovirus type 5 is uncoupled from polyamine accumulation.
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PMID:Adenovirus type 5 induces progression of quiescent rat cells into S phase without polyamine accumulation. 717 12

Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir administration was used to treat human head and neck cancer in nude mice. Tumors were generated by transcutaneous needle injection of 6 x 10(6) human squamous carcinoma cells into the floor of the mouth. After 14 days, 10(10) particles of a replication-defective recombinant adenovirus containing the herpes simplex virus thymidine kinase gene (ADV/RSV-tk) were injected directly into the tumors. The mice subsequently received ganciclovir injections for six consecutive days and were sacrificed at 21 days post tumor cell implantation. Clinical response to the treatment was assessed by computer-imaged morphometric analysis of cross sectional area of nonnecrotic tumor and mitotic activity, which were used for the calculation of a tumor index. The median tumor index value of the treatment group was 280- to 2400-fold smaller than controls which did not receive the therapeutic gene (P < 0.001-0.016), and three-quarters of the treatment group had tumor index values that were indicative of near total tumor regression. Survival studies show that 50% of the ADV/RSV-tk-treated mice are free of tumor at 160 days post adenovirus injection, while all controls died or required sacrifice within 43 days. These results demonstrate that clinically effective in vivo treatment of human squamous cell cancer can be achieved using adenovirus-mediated gene therapy.
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PMID:Adenovirus-mediated gene therapy for human head and neck squamous cell cancer in a nude mouse model. 786 92

Lung cancer is a leading cause of cancer death and standard chemotherapies are resulting in only marginal improvements in outcome. Experimental approaches involving gene therapy are attractive in this clinical setting. There are two basic types of genes utilized, either those intended to induce immunity or those that are directly tumoricidal. Immunity-inducing genes that have been used in model (and some human) systems include MHC molecules, costimulatory molecules, and cytokines such as IL-2, IL-4, IL-6, GM-CSF. These are intended to induce effective systemic immune responses against tumor antigens which would not otherwise develop. Direct toxic approaches include the reintroduction of tumor suppressor genes or enzymes which convert non-toxic drugs to toxic ones, such as herpes thymidine kinase. As a means for gene delivery, retroviruses are the most common vehicle, although Adenovirus vectors and direct DNA delivery have specific advantages.
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PMID:Gene therapy for lung cancer. 861 19

Efficacy and toxicity of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by administration of ganciclovir were studied in vivo. A human epithelial ovarian cancer animal model was established in nude mice using the serous ovarian adenocarcinoma cell line Ov-ca-2774. Intraperitoneal (ip) injection of 1 x 10(8) Ov-ca-2774 cells resulted in tumor growth and formation of malignant ascites in all 15 animals. In a prospective randomized experimental design mice were treated 1, 3, or 7 days after ip injection of 1 x 10(8) cells with ip injection of 2 x 10(8), 6.7 x 10(8), or 2 x 10(9) pfu ADV.RSV-TK followed by administration of ganciclovir (10 microgram /ml, ip, bid) for 6 consecutive days. End points were survival and toxicity. Mice treated with GCV or HSV-TK alone died from 14.4 +/- 1.7 to 19.5 +/- 3.5 days after treatment as did untreated controls. No toxicity of ADV.RSV-TK was found up to 2 x 10(9) pfu (2 x 10(11) particles). The mice with the highest tumor burden treated with the lowest viral dose lived significantly longer than controls (P < 0.05). Median survival in all other groups of mice treated with ADV.RSV-TK plus GCV was even longer (P < 0.01). Treatment benefit was dependent on ADV/RSV-TK dose and tumor burden. Adenovirus-mediated thymidine kinase gene therapy is a realistic approach to ovarian cancer treatment that warrants investigation in the clinical setting.
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PMID:In vivo gene therapy of ovarian cancer by adenovirus-mediated thymidine kinase gene transduction and ganciclovir administration. 862 29

In this study, the growth of locally disseminated breast cancer was modeled using a human breast cancer cell line, MDA-MB-435A, adapted to grow as an ascites tumor in athymic mice. Ex vivo infection of MDA-MB-435A cells with adenovirus containing the herpes simplex virus thymidine kinase gene (HSV-tk) were injected into the intraperitoneal cavity of athymic mice. Ganciclovir (GCV) treatment resulted in prolonged median survival (117 vs. 34 days, p < 0.001) compared to untreated or control animals. Adenovirus containing HSV-tk also demonstrated therapeutic activity after in vivo transduction resulting in prolongation of median survival after GCV treatment (32 vs. 25 days, p < 0.001). However, compared to ex vivo treatment, the effect was modest. In an attempt to increase survival, the viral dose was increased three-fold. Instead of prolonging survival, the increased dose resulted in more toxic deaths. Necropsy demonstrated that the most significant histologic abnormality was marked, diffuse, cytomegalic changes in the liver. Polymerase chain reaction (PCR) analysis of hepatic DNA demonstrated the presence of the virus in the affected tissue. Similar host toxicity and hepatic abnormalities were seen in non-tumor-bearing mice treated with ADV/RSV-tk plus GCV. In conclusion, adenoviral vectors can successfully transfer genes in vivo to cancer cells growing as ascites tumors. Transduction with HSV-tk followed by GCV treatment can prolong survival in this model system of disseminated disease, however toxicity can be substantial. Further refinement in targeting expression of HSV-tk will be required to enhance the therapeutic benefit.
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PMID:Adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase in an ascites model of human breast cancer. 879 49

It is critical to develop new therapies, such as gene therapy, which can impact on both local and metastatic prostate cancer progression. We have developed an orthotopic mouse model of metastatic prostate cancer using a cell line (RM-1) derived from the mouse prostate reconstitution (MPR) model system. This mouse model closely simulates the anatomical and biological milieu of the prostate and allows for realistic testing of experimental gene therapy protocols. Adenovirus (ADV)-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene in conjunction with ganciclovir (GCV) in this model led to significant suppression of growth and of spontaneous metastasis at 14 days post-tumor inoculation. Longer-term studies produced a significant survival advantage and a continued suppression of metastatic activity for treatment animals despite regrowth of the primary tumor. Challenge by injection of tumor cells into the tail vein following excision of treated and control s.c. primary tumors resulted in 40% reduction in lung colonization in the treatment group, indicating the possible production of systemic anti-metastatic activity following a single in situ treatment with ADV/HSV-tk + GCV in this model system.
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PMID:Adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy leads to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. 900 58

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Most patients have obvious metastases or locally advanced disease at the time of presentation. Surgical resection does not significantly change the clinical outcome. Combination chemotherapy induces a partial response but overall survival remains low. The aim of this study was to evaluate the feasibility of adenovirus-mediated suicide gene transduction as a therapeutic approach for pancreatic cancer. A cell line was established from a murine pancreatic ductal adenocarcinoma and intrahepatic tumors were generated by inoculation of pancreatic cancer cells into the left lateral liver lobe. Transduction efficiency was characterized in vitro and in vivo. Intrahepatic tumors were treated by intratumoral adenovirus injection in combination with intraperitoneal administration of ganciclovir. Adenovirus-mediated herpes simplex virus (HSV)-thymidine kinase (tk) gene expression followed by ganciclovir treatment was highly efficient in inhibiting pancreatic cancer cell proliferation in vitro. The proliferation of nontransduced cells was significantly reduced in the presence of HSV-tk expressing cells. Intrahepatic inoculation of pancreatic cancer cells leads to successful formation of solid adenocarcinomas in syngeneic recipients. Ad.RSV-tk injection of the tumor followed by intraperitoneal ganciclovir application caused highly significant tumor volume reduction and necrosis. These results indicate that transduction of the HSV-tk gene followed by ganciclovir is highly efficient for growth inhibition of hepatic metastases of pancreatic carcinoma.
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PMID:Adenoviral-mediated herpes simplex virus thymidine kinase gene transfer: regression of hepatic metastasis of pancreatic tumors. 921 89


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