Jun Yokota

..Thus, identification of environmental as well as genetic factors inducing or suppressing the occurrence of such alterations would be a clue to find novel ways of lung cancer prevention...

..10) were lower than that of adenocarcinoma (OR of 0.39) in group 4. These results suggest that the CYP2A6 is one of the principal determinants affecting not only smoking behavior but also susceptibility to tobacco-related lung cancer...

..Here, I review the progress on molecular studies of tumor progression and metastasis of the past 20 years and discuss the future direction in this field of science...

..Further functional and biological studies of the MYO18B gene will help us understand the molecular pathway of human lung cancer progression...

..The present results suggest that these 4 SNPs function as genetic factors underlying lung cancer susceptibility by modulating activities to maintain the genome integrity of each individual...

..04) and, thus, would be involved in invasion and/or metastasis of adenocarcinoma cells and useful for the prediction of prognosis of patients with small-sized lung adenocarcinoma...

..These results suggest that the chromosome 19q13.3 region encompassing D19S246 contains a gene(s) of which the genetic polymorphisms are associated with lung adenocarcinoma risk and are in linkage disequilibrium with the D19S246 locus...

..Thus, KRAS polymorphisms were indicated to be involved in risk for the development of AAHs that progress to ADC by causing differential KRAS oncogene expression in the lungs...

..These results indicate that the MYO18B gene is a strong candidate for a novel tumor suppressor gene whose inactivation is involved in lung cancer progression...

..Thus, the pathogenetic and biologic significance of TP14ARF inactivation is different between NSCLC cells with wild-type TP53 and those with mutated TP53...

..Thus, it was indicated that mutations in the MSH6 gene, and not in the POLD1 gene, are primarily responsible for the elevated mutation rates in DLD-1 cells...

..These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma...

..These results indicate that this biphasic tumor is of monoclonal origin and the phenotypic heterogeneity of the tumor is due to the differences in the accumulated genetic alterations in each component of the tumor...

..The purpose of this study is to investigate the authenticity of these models by comparison of accumulated genetic alterations between primary and corresponding metastatic lung cancers...

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..Therefore, significance of these functional polymorphisms was evaluated in a population, in which polymorphisms in the GWAS genes showed associations with lung SQC risk...

..These results strongly indicate that the MMP15 and MX2 genes could be novel markers for molecular diagnosis and therapy of lung AdC...

..43 (95% CI = 1.11-1.84, P = 0.0045). These results indicate that OGG1-326Cys functions as a risk allele for lung ADC development...

..The purpose of this study was to elucidate the prevalence and the timing for the occurrence of p16 HDs in lung adenocarcinoma progression in vivo...

..Thus, the present results suggest that genetic and epigenetic inactivation of DOCK8 is involved in the development and/or progression of lung and other cancers by disturbing such regulations...

..Loss of CDCP1 also inhibited the metastatic potential of the A549 cells in vivo. Our findings indicate that CDCP1 is a novel target for treating cancer-specific disorders, such as metastasis, by regulating anoikis in lung adenocarcinoma...

..Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis...

..The present results suggest that MYO18B alterations, including both epigenetic and genetic alterations, play an important role in ovarian carcinogenesis...

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..76 (95% CI = 2.53-9.47, P = 4.2 x 10(-7)). The present results indicated that individuals susceptible to lung ADC can be defined by combined genotypes of HLA-DQA1 and TERT...

..4 × 10(-11), OR = 1.20) and 6p21.3 (rs3817963, P(combined) = 2.7 × 10(-10), OR = 1.18). These data provide further evidence supporting a role for genetic susceptibility in the development of lung adenocarcinoma...

..These results strongly indicate that LKB1 inactivation triggers EMT in lung cancer cells through the induction of ZEB1...

..The present study provides a list of protein- and miRNA-encoding genes whose inactivation is possibly involved in lung carcinogenesis...

..In this study, we investigated the pathogenetic and clinicopathological significances of RASSF1A methylation in the development and/or progression of lung adenocarcinoma...

..The purpose of this study was to identify genetic alterations that define prognosis of patients with early-stage lung ADC...

..Therefore, carcinogens in tobacco smoke, which are activated by NQO1 and detoxified by GSTT1, could have a role in lung adenocarcinoma development...

..0 (95% CI: 1.2-3.2, P=0.002). The present results indicate that inter-individual differences in MTH1 activities due to SNPs are involved in susceptibility to SCLC...

..These results indicate that EGFR mutations are present frequently in brain metastases and occur preceding brain metastasis. These findings will be highly informative for treatment of metastatic lung adenocarcinoma to the brain...

..These results suggest that genetic and epigenetic inactivation of the MYO18B gene play an important role in colorectal carcinogenesis...

..This specific property due to EGFR mutation could be an important step of multistage lung cancer progression...

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..To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy in patients with non-small-cell lung cancer (NSCLC)...

..These results strongly indicate that CHRNA SNPs confer lung cancer susceptibility in a small subset of Japanese in a smoking-independent manner...

..It was also indicated that two broken DNA ends are rejoined by nonhomologous end-joining repair, preferentially utilizing microhomologies of DNA ends, in the occurrence of 9p21 deletions...

..Thus, it was indicated that 9p is the most frequent target of homozygous deletions in lung cancer, suggesting that the arm contains multiple lung tumor suppressor genes and/or genomic features fragile during lung carcinogenesis...

..These results indicate that OGG1 and MYH function as suppressors for G:C to T:A transversions by 8OHG but not by BPDE in human cells...

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..079) in a population of 363 postmenopausal women without cancer. These results indicate that CYP19A1 polymorphisms are involved in the risk for lung AAH and BAC in the lungs by causing differences in estrogen levels...

..These results indicate that HPV 16/18/33 infection does not play a major role in the development of lung AdC in Japan nor in the USA...

..Thus, this assay will be helpful in studies on mechanisms and inter-cellular variations of DSB repair...

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..These results indicate that the PAS1 locus is located in the vicinity of D12S1034 and a genetic variation(s) at this locus is involved in susceptibility to human lung adenocarcinoma...

..These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development...

..EGFR mutations are present frequently in BACs, and are thus likely to be a critical genetic alteration for the formation of noninvasive lung adenocarcinoma...

..These results indicate that both ADR and IL-12 are effective agents against pulmonary metastatic osteosarcoma, and that these sublines are useful for studies on the biological behavior and treatment of pulmonary metastatic osteosarcoma...

..These results suggest that ATM phosphorylates a noncanonical serine residue on p53 by mechanisms different from those for the phosphorylation of Ser15...

..Collectively, we demonstrate a novel molecular difference and simultaneously suggest a difference in the tumor-suppressing function of the variants...

..The ability to detecting such mutations using immunohistochemistry (IHC) would be advantageous...

..the study of family history and spousal history of cancer may play an important role in the assessment of causation of this severe gastric cancer...

..These data show that PRSG can provide a sufficient amount of genomic sequence for a variety of genetic analyses as well as for long-term storage for future work...

..5. Thus, Myo18B is a unique unconventional myosin that is predominantly expressed in myocytes and whose expression is essential for the development and/or maintenance of myofibrillar structure...

..These results indicated that illegitimate V(D)J recombination, which was targeted at several ectopic recombination signal sequences widely distributed in 9p21, caused a large fraction of 9p21 deletions in lymphoid leukemia...

..Taken together, we propose that ana functions as a tumor suppressor and that its product inhibits tumor progression as well by suppressing angiogenesis, invasion, and metastasis...

..Surprisingly, this mutation had little effect on receptor-mediated endocytosis. Thus, the function-specific mutation of CHC will clarify physiological roles of CHC in the regulation of the p53 pathway...

..Further structural analysis of other hot spots of chromosomal DNA breaks as well as the evaluation of the activity and specificity of NHEJ in human cells will elucidate the mechanisms of chromosome interstitial deletions in human cells...

..The results suggest that the increase in DSBs makes the cell more predominant for MMEJ. MMEJ might function as a salvage pathway for DSBs that cannot be repaired by NHEJ...

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..Thus, inhibition of NRF2 may provide new therapeutic approaches in lung cancers with activation of Nrf2...

..We have recently identified the ICAT gene, which encodes a small protein that interacts with beta-catenin and represses Wnt signaling...

..These findings suggest that enhanced activity of Src family kinases and overexpression of paxillin synergistically contribute to the high metastatic potential of human osteosarcoma through the hyperphosphorylation of paxillin...

..Expression of HOMER2 enhanced the ability of MYO18B to suppress anchorage-independent growth. These results indicate that HOMER2 and MYO18B cooperate together in tumor suppression...

..This method could help us understand the pathogenic significance of differential susceptibility to DSBs among genomic regions in human carcinogenesis...

..Case-control studies, mainly focusing on the genes involved in drug metabolisms and DNA repair, have shown that dozens of genes are associated with cancer risks...

..Further investigations are warranted concerning the role of cox-2 and laminin-5 in cancer cell invasion and the significance of p53 and EGFR signaling in the regulation of cox-2 and laminin-5 expression...

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..The present result indicates that the ATF-2 gene is not a major tumor suppressor gene on chromosome 2q, however, it is possible that ATF-2 alterations may be involved in the development of a small subset of lung cancers...

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..Moreover, both forms of lactoferrin failed to substantially modulate the expression of other genes. Thus, lactoferrin does not seem to directly control gene expression or inhibit tumor cell growth...

..Thus, ATF-2 acts as a tumor susceptibility gene of mammary tumors, at least partly, by activating a group of target genes, including Maspin and Gadd45alpha...

..These results suggest that OCIAD2 begins to express at the progression from in situ to invasive carcinoma, and is associated with the favorable prognosis of adenocarcinoma mixed subtype with BAC component...

..These findings suggest that the restored expression of MYO18B may be a useful therapeutic strategy for the treatment of locally advanced MPM in humans...

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..These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer...

..Interestingly, the enhanced expression of AMFR produced tumors in nude mice. Our findings provide a direct evidence that overexpression of the AMFR is associated with the acquisition of a transformation phenotype...

..These results suggest that three alleles of the hOGG1 gene efficiently suppress chemically induced and spontaneously occurring oxidative mutagenesis, and that hOGG1-Gln46 may have a weaker ability to suppress the mutations...

..These data suggest that male smokers possessing the *1A/*1A genotype have higher risk for tobacco-induced lung cancers...

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..Collectively, these results suggested that MYO18B is a substrate for proteasomal degradation...

..We examined whether the cytokine gene expression profile of noncancerous lung tissue could predict the metastatic capability of adjacent lung adenocarcinoma...

..However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking...

..In conclusion, our data strongly support that BRG1 is a bona fide tumor suppressor and a major factor in lung tumorigenesis...

..These findings indicate that TCF8 has a tumor suppressor role in ATLL...