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| 1 | Two distinct pathways of p16 gene inactivation in gallbladder cancer显示文摘AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression,loss of heterozygosity (LOH),homozygous deletion and promoter hypermethylation using immunohistochemistry,microsatellite analysis,quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR,respectively. In addition,mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2,LOH at 9p21-22,p16 promoter hypermethylation,and loss of p16 protein expression were detected in 26.0% (13/50),56.9% (29/51),72.5% (37/51) and 62.7% (32/51),respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene,a combination LOH and promoter hypermethylation,and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene,respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion,a combination of LOH and promoter hypermethylation,and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer. | Hiroyuki Tadokoro Takako Shigihara Tomomi Ikeda Masaru Takase Masafumi Suyama | 2007 | World Journal of Gastroenterology2007，13，47： | 6 |
| 2 | Berchemolide,a novel dimeric vanillic acid glucoside from Berchemia racemosa 显示文摘 | Sakurai N Kobayashi M Shigihara A | 1992 | Chem Pharm Bull1992，40，4： | 1 |
| 3 | Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis显示文摘 | Lee YS Shin S Shigihara T etal | 2007 | Diabetes2007，56，6： | 1 |
| 4 | Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis显示文摘 | Lee YS Shin S Shigihara T | 2007 | Diabetes2007，56，： | 1 |
| 5 | Increased risk of renal deterioration associated with low e-GFR in type 2 diabetes mellitus only in albuminuric subjects显示文摘 | Meguro S Shigihara T Kabeya Y | 2009 | Intemal Medicine2009，48，65： | 1 |
| 6 | Whole-Body Gallium-67 Scintigraphic Findings in IgG4-Related Disease显示文摘 | Shirou Ishii Fumio Shishido Masayuki Miyajima Koutarou Sakuma Takeshi Shigihara Ken Kikuchi | 2011 | Clinical Nuclear Medicine2011，，7： | 1 |
| 7 | Transcriptome profile of Trypanosoma eruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters 显示文摘 | Shigihara T Hashimoto M Shindo N et 01 | 2008 | Parasitol Res2008，102，4： | 1 |
| 8 | Glucagon- like peptide- 1 gene therapy in obese diabetic mice results in long - term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis 显示文摘 | Lee YS Shin S Shigihara T | 2007 | Diabetes2007，56，6： | 1 |
| 9 | Gene expression profile in diabetic KK/Ta mice显示文摘 | Fan Q Shike T Shigihara T | 2003 | Kidney Int2003，64，6： | 1 |
| 10 | Gene expression profile in diabetic KK/Ta mice显示文摘 | Fan QL Shike T Shigihara T | 2003 | Kidney Int2003，64，6： | 1 |
| 11 | Comparison of Alzheimer’s disease with vascular dementia and non-dementia using specific voxel-based Z score maps显示文摘 | Shirou Ishii Fumio Shishido Masayuki Miyajima Koutarou Sakuma Takeshi Shigihara Tadanobu Tameta Makoto Miyazaki Hiroshi Kuroda | 2009 | Annals of Nuclear Medicine2009，，1： | 1 |
| 12 | Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis显示文摘 | Lee YS Shin S Shigihara T | 2007 | Diabetes2007，56，6： | 1 |
| 13 | Antireflection coating for laser diodes显示文摘 | Aoyagi T Kakimoto S | 1995 | Electronics Letters1995，31，18： | 1 |
| 14 | Acylated cyanidin 3-sambubioside-5-glucosides in three garden plants of the Cruciferae显示文摘 | Fumi Tatsuzawa Norio Saito Koichi Shinoda Atsushi Shigihara Toshio Honda | 2006 | Phytochemistry2006，，12： | 1 |
| 15 | Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis 显示文摘 | Lee YS Shin S Shigihara T | 2007 | Diabetes2007，56，6： | 1 |
| 16 | Increased risk of renal deterioration associated with low e-GFR in type 2 diabetes mellitus only in albuminuric subjects显示文摘 | Meguro S Shigihara T Kabeya Y | 2009 | Internal Medicine2009，48，9： | 1 |
| 17 | Mutations in ATP2A2 in patients with Darier's disease 显示文摘 | Ikeda S Mayuzumi N Shigihara T | 2003 | J Invest Dermatol2003，121，3： | 1 |
| 18 | Mutations of ATP2C1 in Japanese patients with Hailey-Hailey disease: intrafamilial and interfamilial phenotype variations and lack of correlation with mutation patterns显示文摘 | Ikeda S Shigihara T Mayuzumi N | 2001 | J Invest Dermatol2001，117，6： | 1 |
| 19 | Berchemolid,a novel dimeric vanillic acid glucoside from Berchemia racemosa显示文摘 | Sakurai N Kobayashi M Shigihara A | 1992 | Chem Pharm Bull1992，40，4： | 1 |
| 20 | Human IAPP-induced pancreatic beta cell toxicity and its regulation by autopbagy显示文摘 | Shigihara N Fukunaka A Hara A et ol | 2014 | J Clin Invest2014，124，8： | 1 |
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