{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:06:50Z","timestamp":1777478810454,"version":"3.51.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T00:00:00Z","timestamp":1483574400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2017,3]]},"DOI":"10.1007\/s10620-016-4438-1","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T00:10:14Z","timestamp":1483575014000},"page":"708-714","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Comparative Analysis of Mutational Profile of Sonic hedgehog Gene in Gallbladder Cancer"],"prefix":"10.1007","volume":"62","author":[{"given":"Ruhi","family":"Dixit","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunil Kumar","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit Nandan Dhar","family":"Dwivedi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay Kumar","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,1,5]]},"reference":[{"key":"4438_CR1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1470-2045(03)01021-0","volume":"4","author":"S Misra","year":"2003","unstructured":"Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol. 2003;4:167\u2013176.","journal-title":"Lancet Oncol"},{"key":"4438_CR2","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00595-009-4304-2","volume":"41","author":"T Fujikawa","year":"2011","unstructured":"Fujikawa T, Tanaka A, Abe T, et al. Undifferentiated carcinoma of the common bile duct with intraductal tumor thrombi: report of a case. Surg Today. 2011;41:579\u2013584.","journal-title":"Surg Today"},{"key":"4438_CR3","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/jso.20527","volume":"93","author":"I Roa","year":"2006","unstructured":"Roa I, De Aretxabala X, Araya JC, Roa J. Preneoplastic lesions in gallbladder cancer. J Surg Oncol. 2006;93:615\u2013623.","journal-title":"J Surg Oncol"},{"key":"4438_CR4","first-page":"31","volume":"1","author":"R Dixit","year":"2012","unstructured":"Dixit R, Shukla VK, Pandey M. Molecular alterations in gallbladder cancer. World J Pathol. 2012;1:31\u201334.","journal-title":"World J Pathol"},{"key":"4438_CR5","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/287795a0","volume":"287","author":"C Nusslein-Volhard","year":"1980","unstructured":"Nusslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980;287:795\u2013801.","journal-title":"Nature"},{"key":"4438_CR6","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nature01972","volume":"425","author":"DM Berman","year":"2003","unstructured":"Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846\u2013851.","journal-title":"Nature"},{"key":"4438_CR7","doi-asserted-by":"crossref","first-page":"13630","DOI":"10.1073\/pnas.95.23.13630","volume":"95","author":"D Carpenter","year":"1998","unstructured":"Carpenter D, Stone DM, Brush J, et al. Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci USA. 1998;95:13630\u201313634.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4438_CR8","first-page":"787","volume":"59","author":"P Zaphiropoulos","year":"1999","unstructured":"Zaphiropoulos P, Unden A, Rahnama F, Hollingsworth R, Toftgard R. ptch2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas. Cancer Res. 1999;59:787\u2013792.","journal-title":"Cancer Res"},{"key":"4438_CR9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc796","volume":"2","author":"A Ruiz i Altaba","year":"2002","unstructured":"Ruiz i Altaba A, Sanchez P, Dahmane N. Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer. 2002;2:361\u2013372.","journal-title":"Nat Rev Cancer"},{"key":"4438_CR10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/nrc1229","volume":"3","author":"Pasca Magliano di","year":"2003","unstructured":"Pasca di Magliano M, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nat Rev Cancer. 2003;3:903\u2013911.","journal-title":"Nat Rev Cancer."},{"key":"4438_CR11","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1093\/carcin\/bgi130","volume":"26","author":"X Ma","year":"2005","unstructured":"Ma X, Chen K, Huang S. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis. 2005;26:1698\u20131705.","journal-title":"Carcinogenesis"},{"key":"4438_CR12","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/bjc.2014.625","volume":"112","author":"M Zuo","year":"2015","unstructured":"Zuo M, Rashid A, Churi C, et al. Novel therapeutic strategy targeting the Hedgehog signalling and mTOR pathways in biliary tract cancer. Br J Cancer. 2015;112:1042\u20131051.","journal-title":"Br J Cancer"},{"key":"4438_CR13","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/j.biocel.2010.04.016","volume":"42","author":"H Chang","year":"2010","unstructured":"Chang H, Li Q, Moraes RC, Lewis MT, Hamel PA. Activation of Erk by sonic hedgehog independent of canonical hedgehog signalling. Int J Biochem Cell Biol. 2010;42:1462\u20131471.","journal-title":"Int J Biochem Cell Biol"},{"key":"4438_CR14","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/mc.20516","volume":"48","author":"M Seto","year":"2009","unstructured":"Seto M, Ohta M, Asaoka Y, et al. Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. Mol Carcinog. 2009;48:703\u2013712.","journal-title":"Mol Carcinog"},{"key":"4438_CR15","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0092-8674(00)81268-4","volume":"85","author":"H Hahn","year":"1996","unstructured":"Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85:841\u2013851.","journal-title":"Cell"},{"key":"4438_CR16","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/aps.2012.24","volume":"33","author":"JT Lu","year":"2012","unstructured":"Lu JT, Zhao WD, He W, Wei W. Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway. Acta Pharmacol Sin. 2012;33:691\u2013700.","journal-title":"Acta Pharmacol Sin"},{"key":"4438_CR17","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.272.5268.1668","volume":"272","author":"RL Johnson","year":"1996","unstructured":"Johnson RL, Rothman AL, Xie J, et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996;272:1668\u20131671.","journal-title":"Science"},{"key":"4438_CR18","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.277.5329.1109","volume":"277","author":"LV Goodrich","year":"1997","unstructured":"Goodrich LV, Milenkovic L, Higgins KM, Scott MP. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 1997;277:1109\u20131113.","journal-title":"Science"},{"key":"4438_CR19","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1073733","volume":"297","author":"DM Berman","year":"2002","unstructured":"Berman DM, Karhadkar SS, Hallahan AR, et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science. 2002;297:1559\u20131561.","journal-title":"Science"},{"key":"4438_CR20","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.1038\/sj.onc.1208133","volume":"23","author":"R Kappler","year":"2004","unstructured":"Kappler R, Bauer R, Calzada-Wack J, et al. Profiling the molecular difference between Patched- and p53-dependent rhabdomyosarcoma. Oncogene. 2004;23:8785\u20138795.","journal-title":"Oncogene"},{"key":"4438_CR21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.3563490","volume":"236","author":"KW Kinzler","year":"1987","unstructured":"Kinzler KW, Bigner SH, Bigner DD, et al. Identification of an amplified, highly expressed gene in a human glioma. Science. 1987;236:70\u201373.","journal-title":"Science"},{"key":"4438_CR22","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.1158\/0008-5472.CAN-04-0416","volume":"64","author":"M Kubo","year":"2004","unstructured":"Kubo M, Nakamura M, Tasaki A, et al. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 2004;64:6071\u20136074.","journal-title":"Cancer Res"},{"key":"4438_CR23","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.bcp.2004.04.025","volume":"68","author":"DN Watkins","year":"2004","unstructured":"Watkins DN, Peacock CD. Hedgehog signalling in foregut malignancy. Biochem Pharmacol. 2004;68:1055\u20131060.","journal-title":"Biochem Pharmacol"},{"key":"4438_CR24","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/nature02009","volume":"425","author":"SP Thayer","year":"2003","unstructured":"Thayer SP, di Magliano MP, Heiser PW, et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature. 2003;425:851\u2013856.","journal-title":"Nature"},{"key":"4438_CR25","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/nature02962","volume":"431","author":"SS Karhadkar","year":"2004","unstructured":"Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004;431:707\u2013712.","journal-title":"Nature"},{"key":"4438_CR26","doi-asserted-by":"crossref","first-page":"12561","DOI":"10.1073\/pnas.0404956101","volume":"101","author":"P Sanchez","year":"2004","unstructured":"Sanchez P, Hernandez AM, Stecca B, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA. 2004;101:12561\u201312566.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4438_CR27","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nature01493","volume":"422","author":"DN Watkins","year":"2003","unstructured":"Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature. 2003;422:313\u2013317.","journal-title":"Nature"},{"key":"4438_CR28","first-page":"6.28","volume-title":"Molecular Cloning: A Laboratory Manual","author":"J Sambrook","year":"2001","unstructured":"Sambrook J, Russell DW. Preparation and analysis of eukaryotic genomic DNA. In: Sambrook J, Russell DW, eds. Molecular Cloning: A Laboratory Manual. 3rd ed. New York: Cold Spring Harbor Laboratory Press, Cold Spring Harbor; 2001:6.28\u20136.30.","edition":"3"},{"key":"4438_CR29","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.4161\/cbt.5.11.3458","volume":"5","author":"T Shida","year":"2006","unstructured":"Shida T, Furuya M, Nikaido T, et al. Sonic Hedgehog-Gli1 signaling pathway might become an effective therapeutic target in gastrointestinal neuroendocrine carcinomas. Cancer Biol Ther. 2006;5:1530\u20131538.","journal-title":"Cancer Biol Ther"},{"key":"4438_CR30","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1111\/j.1349-7006.2011.01912.x","volume":"102","author":"H Onishi","year":"2011","unstructured":"Onishi H, Kai M, Odate S, et al. Hypoxia activates the hedgehog signaling pathway in a ligand-independent manner by upregulation of smo transcription in pancreatic cancer. Cancer Sci. 2011;102:1144\u20131150.","journal-title":"Cancer Sci"},{"key":"4438_CR31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/cas.12073","volume":"104","author":"H Iwasaki","year":"2013","unstructured":"Iwasaki H, Nakano K, Shinkai K, et al. Hedgehog Gli3 activator signal augments tumorigenicity of colorectal cancer via upregulation of adherencerelated genes. Cancer Sci. 2013;104:328\u2013336.","journal-title":"Cancer Sci"},{"key":"4438_CR32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jso.20606","volume":"95","author":"K Yanai","year":"2007","unstructured":"Yanai K, Nagai S, Wada J, et al. Hedgehog signaling pathway is a possible therapeutic target for gastric cancer. J Surg Oncol. 2007;95:55\u201362.","journal-title":"J Surg Oncol"},{"key":"4438_CR33","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1007\/s00595-012-0157-1","volume":"42","author":"J Li","year":"2012","unstructured":"Li J, Wu T, Lu J, et al. Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma. Surg Today. 2012;42:770\u2013775.","journal-title":"Surg Today"},{"key":"4438_CR34","first-page":"12","volume":"5","author":"YJ Kim","year":"2012","unstructured":"Kim YJ, Park SB, Park JY, et al. The sonic hedgehog pathway as a treatment target for extrahepatic biliary tract cancer. Mol Med Rep. 2012;5:12\u201316.","journal-title":"Mol Med Rep"},{"key":"4438_CR35","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/01.pai.0000213132.71041.da","volume":"15","author":"KT Jang","year":"2007","unstructured":"Jang KT, Lee KT, Lee JG, et al. Immunohistochemical expression of Sonic hedgehog in intraductal papillary mucinous tumor of the pancreas. Appl Immunohistochem Mol Morphol. 2007;15:294\u2013298.","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"4438_CR36","first-page":"1051","volume":"17","author":"SY Lee","year":"2007","unstructured":"Lee SY, Han HS, Lee KY, et al. Sonic hedgehog expression in gastric cancer and gastric adenoma. Oncol Rep. 2007;17:1051\u20131055.","journal-title":"Oncol Rep"},{"key":"4438_CR37","first-page":"1798","volume":"58","author":"J Reifenberger","year":"1998","unstructured":"Reifenberger J, Wolter M, Weber RG, et al. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 1998;58:1798\u20131803.","journal-title":"Cancer Res"},{"key":"4438_CR38","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1126\/science.276.5313.817","volume":"276","author":"AE Oro","year":"1997","unstructured":"Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EH Jr, Scott MP. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science. 1997;276:817\u2013821.","journal-title":"Science"},{"key":"4438_CR39","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1158\/0008-5472.CAN-03-4040","volume":"64","author":"S Couv\u00e9-Privat","year":"2004","unstructured":"Couv\u00e9-Privat S, Le Bret M, Traiffort E, et al. Functional analysis of novel sonic hedgehog gene mutations identified in basal cell carcinomas from Xeroderma pigmentosum patients. Cancer Res. 2004;64:3559\u20133565.","journal-title":"Cancer Res"},{"key":"4438_CR40","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.humpath.2013.10.017","volume":"45","author":"F Xie","year":"2014","unstructured":"Xie F, Xu X, Xu A, et al. Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma. Hum Pathol. 2014;45:513\u2013521.","journal-title":"Hum Pathol"},{"key":"4438_CR41","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/hed.21437","volume":"33","author":"S Schneider","year":"2011","unstructured":"Schneider S, Thurnher D, Kloimstein P, et al. Expression of the sonic hedgehog pathway in squamous cell carcinoma of the skin and the mucosa of the head and neck. Head Neck. 2011;33:244\u2013250.","journal-title":"Head Neck"},{"key":"4438_CR42","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1600-0625.2006.00473.x","volume":"15","author":"M Athar","year":"2006","unstructured":"Athar M, Tang X, Lee JL, Kopelovich L, Kim AL. Hedgehog signalling in skin development and cancer. Exp Dermatol. 2006;15:667\u2013677.","journal-title":"Exp Dermatol"},{"key":"4438_CR43","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/ng916","volume":"31","author":"MD Taylor","year":"2002","unstructured":"Taylor MD, Liu L, Raffel C, et al. Mutations in SUFU predispose to medulloblastoma. Nat Genet. 2002;31:306\u2013310.","journal-title":"Nat Genet"},{"key":"4438_CR44","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1093\/hmg\/8.13.2479","volume":"8","author":"L Nanni","year":"1999","unstructured":"Nanni L, Ming JE, Bocian M, et al. The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet. 1999;8:2479\u20132488.","journal-title":"Hum Mol Genet"},{"key":"4438_CR45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/ajmg.a.10163","volume":"117A","author":"M Marini","year":"2003","unstructured":"Marini M, Cusano R, De Biasio P, et al. Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability. Am J Med Genet A. 2003;117A:112\u2013115.","journal-title":"Am J Med Genet A"},{"key":"4438_CR46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/1098-1004(200008)16:2<99::AID-HUMU2>3.0.CO;2-0","volume":"16","author":"D Wallis","year":"2000","unstructured":"Wallis D, Muenke M. Mutations in holoprosencephaly. Hum Mutat. 2000;16:99\u2013108.","journal-title":"Hum Mutat"}],"container-title":["Digestive Diseases and Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-016-4438-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10620-016-4438-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-016-4438-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,25]],"date-time":"2017-06-25T03:16:52Z","timestamp":1498360612000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10620-016-4438-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,5]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["4438"],"URL":"https:\/\/doi.org\/10.1007\/s10620-016-4438-1","relation":{},"ISSN":["0163-2116","1573-2568"],"issn-type":[{"value":"0163-2116","type":"print"},{"value":"1573-2568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,5]]}}}