ABSTRACT
PURPOSE: Microsatellite instability (MSI) is frequently used as an indicative of microsatellite mutator phenotype (MMP) tumors. MSI has been observed in a fraction of non-small cell lung cancer (NSCLC). However, its role in tumorigenesis of NSCLC remains unknown. We evaluated the frequency and pattern of MSI in NSCLC, and compared the clinical parameters of MSI-positive tumors with those of MSS (microsatellite stable) tumors. MATERIALS AND METHODS: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosome 3p and 9p. Patients' peripheral blood lymphocytes were used as the source of the normal DNA. RESULTS: 1) Of 20 cases, 8 (40%) demonstrated MSI. 2) Instability observed more commonly in tri- and tetra-nucleotide repeats rather than dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LOH was observed in 10 (50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor (showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors (showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI-negative tumors in clinicopathologic features such as pack-year history of smoking, histologic subtype, and the stage of disease. There was also no significant difference in the incidence of LOH according to the status of MSI. CONCLUSION: These data strongly suggest that MSI has different roles in lung and colon cancer. MMP pathway appears far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.
Subject(s)
Carcinogenesis , Carcinoma, Non-Small-Cell Lung , Colonic Neoplasms , Dinucleotide Repeats , DNA , Incidence , Lung , Lymphocytes , Microsatellite Instability , Microsatellite Repeats , Phenotype , Smoke , Smoking , Tobacco ProductsABSTRACT
BACKGROUND: Recombinant adenovirus hold promise as vectors to carry therapeutic genes for several reasons: 1) they can infect both dividing and non-dividing cells ; 2) they have the ability to directly transduce tissues in vivo; 3) they can easily be produced in high titer ; and 4) they have an established record of safety as vaccination material. However, one of the major limitation in the use of adenoviruses is that transgene expression is quite short because adenovirusees insert their DNA genome episomally rather than by chromosomal integration, and an immune response against the virus destroys cells expressing the therapeutic gene. Since sodium butyrate has been reported to induce adenovirus-mediated gene expression, we hypothesized that treatment of tumor cells, transduced with herpes simples virus thymidine kinase(HSVtk) gene using adenoviral vector, with butyrate could augment the effect of gene therapy. METHODS: We transduced HSVtk gene, driven by the cytomegalovirus promoter, into REN cell line(human mesothelioma cell line). Before proceeding with the comparison of HSVtk/ganciclovir mediated bystander killing, we evaluated the effect of butyrate on the growth of tumor cells in order to rule out a potential antitumor effect of butyrate alone, and also on expression of HSVtk gene by Western blot analysis. Then we determined the effects of butyrate on bystander-mediated cell killing in vitro. RESULTS: There was no inhibition of growth of cells exposed to butyrate for 24 hours at a concentration of 1.5mM/L. Toxic effects were seen when the concentration of butyrate was greater than 2.0mM/h Gene expression was more stable and bystander effect was augmented by butyrate treatment of a concentration of 1.5mM CONCLUSION: These results provide evidence that butyrate can augment the efficiency of cell killing with HSVtk/GCV system by inducing transgene expression and may thus by a promising new approach to improve responses in gene therapy using adenoviral vectors.
Subject(s)
Adenoviridae , Blotting, Western , Butyrates , Butyric Acid , Bystander Effect , Cytomegalovirus , DNA , Gene Expression , Genetic Therapy , Genome , Herpes Simplex , Homicide , Mesothelioma , Phosphotransferases , Simplexvirus , Thymidine , Transgenes , VaccinationABSTRACT
Carcinoid tumors are well-differentiated epithelial neoplasms that usually can be diagnosed without difficulty based on their distinctive histologic patterns. These tumors are composed of variable numbers of calls that contain endocrine secretory granules in their cytoplasm, which can be identified by histochemistry, immunohistochemistry, and electron microscopy, Carcinoid tumors of the duodenum are relatively rare, the reported incidence being 2.0-8.9% of all gastrointestinal carcinoid tumors dianosed in Western countries. The rate of occurrence among all duodenal tumors is 3-5.5%. We experienced a case of carcinoid tumor of the duodenum in a 53 year-old male patient. He was admitted to our hospital because of epigastric pain. On the gastrofiberscopic examination, 0.7 cm sized Yamada type II polyp with central ulceration was noticed on the duodenal bulb. The biopsy specimen revealed carcinoid tumor. He was treated with polypectomy.