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| 1 | Cancer-associated fibroblast-derived secreted phosphoprotein 1 contributes to resistance of hepatocellular carcinoma to sorafenib and lenvatinib显示文摘Background:Cancer-associated fibroblasts(CAFs)play an important role in the induction of chemo-resistance.This study aimed to clarify the mechanism underlying CAF-mediated resistance to two tyrosine kinase inhibitors(TKIs),sorafenib and lenvatinib,and to identify a novel therapeutic target for overcoming TKI resistance in hepatocellular carcinoma(HCC).Methods:We performed a systematic integrative analysis of publicly available gene expression datasets and whole-transcriptome sequencing data from 9 pairs of CAFs and para-cancer fibroblasts isolated from human HCC and para-tumor tissues,respectively,to identify key molecules that might induce resistance to TKIs.We then performed in vitro and in vivo experiments to validate selected targets and related mechanisms.The associations of plasma secreted phosphoprotein 1(SPP1)expression levels before sorafenib/lenvatinib treatment with progression-free survival(PFS)and overall survival(OS)of 54 patients with advanced HCC were evaluated using Kaplan-Meier and Cox regression analysis.Results:Bioinformatic analysis identified CAF-derived SPP1 as a candidate molecule driving TKI resistance.SPP1 inhibitors reversed CAF-induced TKI resistance in vitro and in vivo.CAF-derived SPP1 activated rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)through the integrin-protein kinase C-alpha(PKCα)signaling pathway and promoted epithelial-to-mesenchymal transition(EMT).A high plasma SPP1 level before TKI treatment was identified as an independent predictor of poor PFS(P=0.026)and OS(P=0.047)in patients with advanced HCC after TKI treatment.Conclusions:CAF-derived SPP1 enhances TKI resistance in HCC via bypass activation of oncogenic signals and EMT promotion.Its inhibition represents a promising therapeutic strategy against TKI resistance inHCC.Moreover,plasma SPP1 level before TKI treatment represents a potential biomarker for treatment response prediction. | JungWoo Eun Jung Hwan Yoon Hye Ri Ahn Seokhwi Kim Young Bae Kim Su Bin Lim Won Park TaeWook Kang Geum Ok Baek Moon Gyeong Yoon Ju A Son Ji HyangWeon Soon Sun Kim Hyo Jung Cho Jae Youn Cheong | 2023 | Cancer Communications2023，43，4： | 2 |
| 2 | Comparison of Endoscopic Papillary Balloon Dilation and Sphincterotomy in Young Patients with CBD Stones and Gallstones显示文摘 | Yu Ri Seo Jong Ho Moon Hyun Jong Choi Dong Choon Kim Ji Su Ha Tae Hoon Lee Sang-Woo Cha Young Deok Cho Sang-Heum Park Sun-Joo Kim | 2014 | Digestive Diseases and Sciences2014，，5： | 2 |
| 3 | Papillary balloon dilation is not itself a cause of post‐endoscopic retrograde cholangiopancreatography pancreatitis; results of anterograde and retrograde papillary balloon dilation显示文摘 | Yu Ri Seo Jong Ho Moon Hyun Jong Choi Dong Choon Kim Tae Hoon Lee Sang‐Woo Cha Young Deok Cho Sang‐Heum Park Sun‐Joo Kim | 2013 | J Gastroenterol Hepatol2013，，8： | 2 |
| 4 | Rheological and electtrical properties of polypropylene composites containing functionalized multi-walled carbon nanotubes and comrpatibilizers显示文摘 | Lee Seung H w an Cho Eun Na Ri | | 0，，： | 1 |
| 5 | Styelins, Broad-Spectrum AntimicrobialPeptides from the Solitary Tunicate,Styelaclava 显示文摘 | Lee IH Cho Y Lehrer RI | 1997 | Comp BiochemPhysiol B Biochem Mol Biol1997，118，3： | 1 |
| 6 | Intraoperative fluoroscopy- guided removal of orbital foreign bodies 显示文摘 | Cho RI Kahana A Patel B | 2009 | Ophthal Plast Reeonstr Surg2009，25，： | 1 |
| 7 | An anti-apoptotic protein human survivin is a direct inhibitor of easpase-3 and-7显示文摘 | Shin S Sung RI Cho YS | 2001 | Biochemistry2001，40，4： | 1 |
| 8 | Ananti-apoptotic protein human surviving is a direct inhibitor of caspase-3 and caspase-7显示文摘 | Shin S Sung RI Cho YS | 2001 | Biochemistry2001，40，4： | 1 |
| 9 | Improvements of Thorp - Rolewicz theorems on operator series 显示文摘 | LI Rong - lu CUI Cheng - ri CHO MIN - HYUNG | 1998 | Bull Korean Math1998，35，1： | 1 |
| 10 | Anatomical basis of glial cell linederived neurotrophic factor expression in the striatum and related basal ganglia during postnatal development of the rat 显示文摘 | Oo T F Ries V Cho J | 2005 | Comp Neurol2005，484，1： | 1 |
| 11 | Neutrophil - derived IL - 1 beta is sufficient for abscess formation in immunity against Staphylococ- cus aureus in mice显示文摘 | Cho JS Guo Y Ramos RI et 81 | 2012 | PLoS Pathog2012，8，10： | 1 |
| 12 | Clinical feasibility of direct peroral cholangioscopy–guided photodynamic therapy for inoperable cholangiocarcinoma performed by using an ultra-slim upper endoscope (with videos)显示文摘 | Hyun Jong Choi Jong Ho Moon Bong Min Ko Seul Ki Min A. Ri Song Tae Hoon Lee Young Koog Cheon Young Deok Cho Sang-Heum Park | 2011 | Gastrointestinal Endoscopy2011，，4： | 1 |
| 13 | Neutrophil-derived IL-lbeta is sufficient for abscess formation in immunity against Staphylococcus aureusin mice 显示文摘 | Cho JS Guo Y Ramos RI | 2012 | PLoSPatbog2012，8，10： | 1 |
| 14 | Anatomical basis of glial cell line-derived neurotrophic factor expression in the striatum and related basal ganglia during postnatal development of the rat显示文摘 | Oo TF Ries V Cho J | 2005 | J Compa Neurol2005，484，1： | 1 |
| 15 | Neutrophil-derived IL-lbeta is sufficient for abscess formation in immunity against Staphylococcus aureus in mice显示文摘 | Cho JS Guo Y Ramos RI | 2012 | PLoS Pathog2012，8，10： | 1 |
| 16 | Effects of ph and salinity on the antimicrobial properties of clavnins显示文摘 | Lee IH Cho Y Lehrer RI | 1997 | Infect Immun1997，65，7： | 1 |
| 17 | Styelins, broad-spectrum antimicrobial peptides from the solitary tunicate, Styela clava显示文摘 | Lee IH Cho Y Lehrer RI | 1997 | Comp Biochem Physiol B Biochem Mol Biol1997，118，3： | 1 |
| 18 | Styelins,broad-spectrum antimicrobial peptides from the solitary tunicate,Styela clava显示文摘 | Cho Y Lethrer RI | 1997 | Comp Biochem Physiol1997，118，3： | 1 |
| 19 | Submucosal injection of poly(lactic-co-glycolic acid) microspheres in rabbit bladder as a potential treatment for urinary incontinence and vesicoureteral reflux: preliminary results显示文摘 | Eui Ri Cho Sun-Woong Kang Heung Jae Park Young Sam Cho You Sik Lee Joon Chul Kim Byung-Soo Kim | 2005 | Journal of Biomaterials Science Polymer Edition2005，，9： | 1 |
| 20 | Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells显示文摘The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial.Here,we developed a novel monoclonal antibody(mAb),called P5,by immunizing mice with human peripheral blood mononuclear cells(PBMC).Its anti-tumor effect is now being tested,in a clinical phase HI trial,in combinatorial treatments with various chemical drugs.To confirm that P5 indeed binds to beta 1 integrin,cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb(TS2/16) and immunoblotted against P5 to reveal a140 kDa molecular weight band,as expected.Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin.Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells,while causing inhibition of cell growth.When cells were co-treated with different concentrations of P5 mAb,the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner.Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30%increase in apoptosis,compared to baseline,and significantly more when compared to either the cisplatin or P5 alone group.The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed.Together,these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma. | Min-Young Kim Woon-Dong Cho Kwon Pyo Hong Da Bin Choi Jeong won Hong Soseul Kim Yoo Ri Moon Seung-Myoung Son Ok-Jun Lee Ho-Chang Lee Hyung Geun Song | 2016 | The Journal of Biomedical Research2016，30，3： | 0 |
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