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991.
992.
Molecular profiling and genome‐wide analysis based on somatic copy number alterations in advanced colorectal cancers 下载免费PDF全文
Tamotsu Sugai MD Yayoi Takahashi MD Makoto Eizuka MD Ryo Sugimoto MD Yasuko Fujita MD Wataru Habano PhD Kouki Otsuka MD Akira Sasaki MD Eiichiro Yamamoto MD Takayuki Matsumoto MD Hiromu Suzuki MD 《Molecular carcinogenesis》2018,57(3):451-461
To characterize somatic alterations in colorectal cancer (CRC), we conducted a genome‐scale analysis of 106 CRC specimens. We assessed comprehensive somatic copy number alterations (SCNAs) in these CRC specimens. In addition, we examined microsatellite instability (MSI; low and high), genetic mutations (KRAS, BRAF, TP53, and PIK3CA), and DNA methylation status (classified into low, intermediate, and high type). We stratified molecular alterations in the CRCs using a hierarchical cluster analysis. The examined CRCs could be categorized into three subgroups using hierarchical cluster analysis. Tumors in subgroup 1 were characterized by a low frequency of SCNAs and a high frequency of MSI‐high status, whereas tumors in subgroups 2 and 3 were closely associated with a high frequency of SCNAs. Tumors in subgroup 1 were preferentially present in the right‐sided colon and showed frequent MSI‐high status. Subgroup 3 was distinguished by specific alterations, including gains at 1q23‐44, 1p11‐36, 10q11‐26, 10p11‐13, 12q24‐24, and 13q33‐33. In contrast, tumors in subgroup 2 were characterized by copy‐neutral LOH at 12p12‐13, 1q24‐25, and 10q22. In addition, KRAS mutations were more frequently found in subgroup 3 than in subgroup 1. TP53 mutations and intermediate levels of DNA methylation were common alterations in the three subgroups. SCNAs contributed to sporadic CRC, and there were three subgroups based on SCNAs that played a different role in driving the development of this disease. 相似文献
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Takahito Chijiwa Emi Tokunaga Ryo Ikeda Koki Terada Tomohisa Ogawa Naoko Oda-Ueda Shosaku Hattori Masatoshi Nozaki Motonori Ohno 《Toxicon》2006,48(6):672-682
Protobothrops (formerly Trimeresurus) elegans, a Crotalinae snake, inhabits Ishigaki and Iriomote islands of the Sakishima Islands of Japan which are located between Okinawa island of Japan and Taiwan. Two phospholipase A(2) (PLA(2)) isozymes were purified to homogeneity from P. elegans venom and sequenced. This led to a discovery of novel PLA(2) isozymes with Arg at position 49, that is, [Arg(49)]PLA(2) forms, named PeBP(R)-I and PeBP(R)-II. They are polymorphic at position 3, Val for PeBP(R)-I and Ile for PeBP(R)-II. The cDNAs encoding PeBP(R)-I and PeBP(R)-II were cloned. The cDNA encoding an [Asp(49)]PLA(2) named PePLA(2) was also obtained. In contrast to PLA(2) isozymes from Protobothrops genus with 122 amino acid residues, PeBP(R)-I and PeBP(R)-II are composed of 121 amino acid residues due to lack of Pro at position 90. They exhibited necrotic and edema-inducing activities but no hemorrhagic activity was detected. A phylogenetic tree constructed for venom PLA(2) isozymes of Protobothrops genus and of related genera in the southwestern islands of Japan and Taiwan revealed that PeBP(R)-I and PeBP(R)-II of P. elegans are evolutionarily much closer to PmK49PLA(2), a [Lys(49)]PLA(2), from P. mucrosquamatus (Taiwan) than BPI and BPII, both [Lys(49)]PLA(2) forms, from P. flavoviridis (Amami-Oshima and Tokunoshima islands of Japan). Such evolutionary relationships are also seen in neutral [Asp(49)]PLA(2) isozymes from the three Protobothrops species. Thus, P. elegans is the species much closer to P. mucrosquamatus than P. flavoviridis. Their evolutionary distances seem to be well related to geological history of the islands where they have lived. In addition, it was clearly noted that Ovophis okinavensis (Amami-Oshima), which had formerly belonged to the Trimeresurus genus, and Trimeresurus stejnegeri (Taiwan) are the species fairly distant from Protobothrops genus. 相似文献
994.
MicroRNA‐143/Musashi‐2/KRAS cascade contributes positively to carcinogenesis in human bladder cancer
Takuya Tsujino Nobuhiko Sugito Kohei Taniguchi Ryo Honda Kazumasa Komura Yuki Yoshikawa Tomoaki Takai Koichiro Minami Yuki Kuranaga Haruka Shinohara Yoshihisa Tokumaru Kazuki Heishima Teruo Inamoto Haruhito Azuma Yukihiro Akao 《Cancer science》2019,110(7):2189-2199
It has been well established that microRNA (miR)‐143 is downregulated in human bladder cancer (BC). Recent precision medicine has shown that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which correlate with RAS signaling networks. We have previously shown that miR‐143 suppresses cell growth by inhibiting RAS signaling networks in several cancers including BC. In the present study, we showed that synthetic miR‐143 negatively regulated the RNA‐binding protein Musashi‐2 (MSI2) in BC cell lines. MSI2 is an RNA‐binding protein that regulates the stability of certain mRNAs and their translation by binding to the target sequences of the mRNAs. Of note, the present study clarified that MSI2 positively regulated KRAS expression through directly binding to the target sequence of KRAS mRNA and promoting its translation, thus contributing to the maintenance of KRAS expression. Thus, miR‐143 silenced KRAS and MSI2, which further downregulated KRAS expression through perturbation of the MSI2/KRAS cascade. 相似文献
995.
Yusuke Yamamoto Hisashi Ikoma Ryo Morimura Hirotaka Konishi Yasutoshi Murayama Shuhei Komatsu Atsushi Shiozaki Yoshiaki Kuriu Takeshi Kubota Masayoshi Nakanishi Daisuke Ichikawa Hitoshi Fujiwara Kazuma Okamoto Chouhei Sakakura Toshiya Ochiai Eigo Otsuji 《World journal of gastroenterology : WJG》2015,21(4):1207-1215
AIM: To determine the best cut-off value between the early and late recurrence periods after the initial recurrence of hepatocellular carcinoma(HCC).METHODS: The clinical records of 404 patients who underwent macroscopic curative hepatectomy for HCC between 1980 and 2010 were retrospectively examined. We divided the 252 patients experienced a recurrence of HCC into two groups, the early and late recurrence groups using the minimum P-value approach. Factors for early recurrence were investigated using all 404 patients, and factors related to late recurrence were investigated in the patients who were confirmed to be recurrence free at the end of the early recurrence period.RESULTS: For the 252 patients who experienced a recurrence, the optimal cut-off value for differentiating early and late recurrence based on the overall survival after initial recurrence was 17 mo(5-year overall survival after initial recurrence: 15.4% vs 36.3%, P = 0.000018). Cox proportional hazard analysis identified early recurrence(P = 0.003) as one of the independent prognostic factors associated with overall survival after initial recurrence. A logistic regression model showed that an alpha-fetoprotein level > 100 ng/m L(P < 0.001), multiple HCC(P < 0.001), serosal invasion(P = 0.031), and microvascular invasion(P = 0.012) were independent factors associated with early recurrence, whereas the only independent factor related to late recurrence was liver cirrhosis(P = 0.002).CONCLUSION: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies. 相似文献
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Possible Role of Protein(s) as Antigenic Determinant of the Type-Specific Main Antigen of Leptospira kremastos Strain Kyoto 下载免费PDF全文
Acid hydrolysates of the type-specific main (TM) antigen isolated from Leptospira kremastos strain Kyoto showed a considerable inhibition of complement fixation reaction between TM antigen and anti-strain Kyoto serum. A fraction of 2 N HCl hydrolysate containing exclusively a large amount of neutral sugars showed no inhibition, whereas another fraction containing only a small amount of protein(s) showed a slight inhibition. The remaining fractions containing amino sugars, protein(s), and neutral sugars showed a slight inhibition, but the inhibition did not correlate with the amount of amino sugars. TM antigen, delipidized by hydrolysis with 1 N HCl for 4 min and then dialysis, showed a strong inhibition. The lipid fraction did not show any inhibition. The inhibitory effect of nondialyzable delipidized TM antigen was completely lost by treating the antigen with proteolytic enzymes, indicating that the antigenic determinant of L. kremastos strain Kyoto is intimately related with protein(s). 相似文献
1000.
Abe O Yamasue H Aoki S Suga M Yamada H Kasai K Masutani Y Kato N Kato N Ohtomo K 《Neurobiology of aging》2008,29(1):102-116
This study investigated the global and regional effects of aging on brain volume, mean diffusivity (MD), and fractional anisotropy (FA) in 73 normal female subjects using voxel-based analysis. On a global scale, gray matter volume and FA were negatively correlated, whereas MD was positively correlated with age. Voxel-wise analyses showed brain volume and FA were negatively correlated predominantly in anterior structures, whereas MD was positively correlated in the cortical gray matter and periventricular white matter. Volume preservation was observed in the cingulate gyrus and subjacent white matter. FA increase was observed in the putamen. Voxel-based direct comparisons of volume and diffusion properties showed FA was more strongly negatively correlated in the fronto-temporal white matter, compared with volume and MD. Stronger positive correlation of MD was observed in the thalamus, caudate nucleus, and midbrain and stronger negative correlation of brain volume was observed in the frontal lobe and basal ganglia, compared with the other. These results indicate that diffusion properties and brain volume are complementary markers to the effects of aging. 相似文献