A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Inhibitory effect of humanized anti-VEGFR-2 ScFv-As_2O_3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma:in vitro and in vivo studies

Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo,which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.Methods:Humanized anli-VECFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology.In this combined in vitro and in vivo study,the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth,invasion,and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay,Tanswell assay,Hochest33258 staining,and DNA ladder analysis.The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402xenografts.Results:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yh-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells.And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis.Transwell assay found that the drug also inhibited the metastasis ability of tumor cells.Furthermore,anti-VEGFR-2 ScFv-As^-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration（92.9%）,followed by As2O3-stealth nanoparticles,anti-VEGFR-2 ScFv,and As203（61.4%,58.8%,20.5%,P【0.05）.The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-steallh nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.