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

Bone marrow endothelial cells are critical mediators in the processes of cell trafficking as well as cancer metastasis, however few established models exist. An immortal cell line of Copenhagen rat bone marrow endothelium was established after infection of primary cultured cells with Adenovirus-12 SV40 hybrid virus and designated YPBE-1. The established cell line has continued to proliferate more than 70 population doublings and has not undergone "crisis". It stains positively for SV40 T-antigen in its nuclei by immunohistochemistry and grows in a monolayer with a cobblestone appearance. It demonstrates Dil-Ac-LDL uptake as an endothelial marker. YPBE-1 does not express Integrin beta 3 or endothelin, but does express Integrin alpha 6 beta 1 on the plasma membrane and demonstrates tube formation in Matrigel. This cell line of rat bone marrow endothelial origin should be useful for studying mechanisms of bone metastasis and cell trafficking.
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PMID:Establishment of an immortalized Copenhagen rat bone marrow endothelial cell line. 883 95

The majority of human solid tumors are likely to express protein epitopes which can act as targets for cytotoxic T cells, but these are frequently not effectively recognized. We tested whether the introduction of the costimulatory molecule B7-1 using a recombinant adenovirus (Ad-B7) can result in effective induction of epitope-specific immunity in two tumor models that express defined endogenous protein epitopes: D459, a fibroblast-derived cell line transfected with a human missense mutant p53 (C to Y at position 135), and P815, a mastocytoma expressing the endogenous tumor epitope P1A. Under the conditions studied, both of these tumors grow and kill their hosts without evidence of significant immune rejection. However, after transduction with the adenovirus containing B7-1, both of these tumors lose tumorigenicity and elicit specific cellular immunity to the mutant p53 epitope in D459 and P1A in P815. In addition, animals exposed to B7-transduced tumor cells were protected from subsequent challenge with nontransduced tumor. Adenovirus has distinct advantages for this approach, as it has high infectivity not requiring in vitro culture, low lytic potential, and transient expression of sufficient duration for immunologic effectiveness but without significant concern over permanent genetic modification. We conclude that transduction of tumor cells with Ad-B7 can increase the immunogenicity of endogenous protein epitopes and may represent a practical therapeutic approach to system human cancers.
Cancer Gene Ther
PMID:Increased immunogenicity of tumors bearing mutant p53 and P1A epitopes after transduction of B7-1 via recombinant adenovirus. 885 48

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.
Int J Cancer 1997 Jan 17
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

The overall goal of this review is to provide the pediatric neurologist with a theoretical foundation in gene therapy. Gene therapy became feasible in the early 1970s and the first transfer of a foreign gene into humans was approved by the NIH in 1989. Adenovirus, adeno-associated virus, herpes-simplex virus, retroviruses, and other vectors have been used to efficiently transduce genes into cells in vitro and in vivo. We discuss laboratory experiments that have provided a strong scientific rationale for implementing human clinical trials of gene therapy for neurologic malignancy. The development of viral and nonviral vectors that mediate efficient gene insertion into human cells has created the prospect of using gene therapy for cancer or brain disease. The NIH has approved more than 100 gene therapy protocols since 1989. However, the field will require more research on gene delivery systems before gene therapy becomes an established therapeutic strategy for an array of central nervous system diseases.
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PMID:Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 1. The bench. 901 Jul 89

Overexpression of the tumour suppressor gene product p53 is common in oesophageal adenocarcinoma. This may be due to gene mutation, but overexpression can also result from complexing between viral proteins and p53; a number of viruses are causally linked with malignancy. This study therefore investigated the prevalence in oesophageal adenocarcinoma of viruses whose gene products are capable of interacting with p53. Seventeen tumours and 17 normal oesophagi were screened for specific DNA sequences from human papilloma virus (HPV), Adenovirus type 12, Epstein-Barr Virus (EBV), and cytomegalovirus (CMV). Frozen sections were analysed by polymerase chain reaction, and results were confirmed by Southern blot hybridization. Overexpression of p53 was studied immunohistochemically. Overexpression of p53 was identified in 11 of 17 tumours. No viral sequences were detected for HPV, CMV, or Adenovirus in any tumour. EBV sequences were found in eight of 17 tumours, and eight of 17 negative controls. There is therefore no evidence of HPV 16, 18 and 33, Adenovirus 12 or CMV infection in oesophageal adenocarcinoma. EBV infection in the oesophagus is of doubtful significance, in view of the high incidence in the control population. Overexpression of p53 cannot be explained by complexing with common viral proteins, and must be related to other intracellular mechanisms.
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PMID:Investigation of oesophageal adenocarcinoma for viral genomic sequences. 906 43

Toxins are effective in cell killing if internalized efficiently. Conjugation of the plant toxin saporin with basic fibroblast growth factor has increased tumor killing due to better internalization, but toxin uptake by cells has remained relatively inefficient. We show here that infection of melanoma cells with a replication-defective adenovirus enhances cell killing by the mitotoxin basic fibroblast growth factor-saporin more than 10-fold, thus allowing tumor cell killing in vivo at nontoxic concentrations. Adenovirus infection leads to increased apoptosis by the mitotoxin due to enhanced internalization of the ligand-receptor complex and release of the active toxin from the endosomes.
Cancer Res 1997 May 15
PMID:Adenovirus infection enhances killing of melanoma cells by a mitotoxin. 915 78

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

Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer (P < 0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins.
J Cancer Res Clin Oncol 1997
PMID:Detection of group C adenovirus DNA in small-cell lung cancer with the nested polymerase chain reaction. 926 May 89

The combination of specific gene targeting technologies with efficient gene delivery systems could provide the means to evaluate the concept of anticancer strategies designed to block expression of potentially rate-limiting tumor promoting factors. Here, we constructed adenoviruses expressing hammerhead-ribozymes targeted to two of these factors, the tyrosine kinase receptor HER-2/neu or the growth factor pleiotrophin (PTN). Adenovirus-mediated transduction of either HER-2/neu- or PTN-targeted ribozymes depleted the respective RNAs and inhibited protein expression significantly in three different human cancer cell lines. This resulted in almost complete abrogation of HER-2/neu- or PTN-dependent cancer-cell proliferation, thus demonstrating the feasibility of this approach as a future cancer gene therapy.
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PMID:Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation. 934 31

Adenovirus infections have been associated with a variety of disorders of the respiratory, ocular, gastrointestinal and urogenital systems. In the last fifteen years, special attention has been given to the adenoviral infections in immunocompromised host, transplant recipients, cancer patients and AIDS patients. Adenoviruses in these patients can cause severe, often generalized illness, with high fatality rate. Data suggest a specific role for adenoviruses in AIDS pathogenesis. From AIDS patients many new and intermediate adenovirus serotypes could be isolated. Considerable effort should be devoted to this area of research in the coming years to understand the molecular mechanism of the interaction between AIDS and adenoviruses. In the last few years recombinant adenoviruses have been widely used as gene delivery vectors in experiments both with curative and preventive purposes. Adenovirus vectors have been used in the experimental gene therapy of genetic disorders, of immuno- and molecular therapy of a variety of cancers. The combination of recombinant adenovirus technology with chemotherapy (pro drug system) seems to be promising, as well as the specific destruction of tumor cells with modified, not recombinant adenoviruses. An the other hand, recombinant adenoviruses appear to be attractive candidates for vaccination against the infectious diseases, too. The current tendency is the construction of second-generation vectors which serve better the different purposes. Potential improvements could be the construction of targated vector by the modification of viral cell-tropism and the suppression of the immune response of the host organism directed against the vector and the vector virus infected cells.
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PMID:[New developments and trends in adenovirus research]. 941 41


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