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| 1 | Diagnostic value of 5 serum biomarkers for hepatocellular carcinoma with different epidemiological backgrounds:A large-scale,retrospective study显示文摘Objective:Hepatocellular carcinoma(HCC)is a lethal global disease that requires an accurate diagnosis.We assessed the potential of 5 serum biomarkers(AFP,AFU,GGT-II,GPC3,and HGF)in the diagnosis of HCC.Methods:In this retrospective study,we measured the serum levels of each biomarker using ELISAs in 921 participants,including 298 patients with HCC,154 patients with chronic hepatitis(CH),122 patients with liver cirrhosis(LC),and 347 healthy controls from 3 hospitals.Patients negative for hepatitis B surface antigen and hepatitis C antibody(called'NBNC-HCC')and patients positive for the above indices(called'HBV-HCC and HCV-HCC')were enrolled.The selected diagnostic model was constructed using a training cohort(n=468),and a validation cohort(n=453)was used to validate our results.Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.Results:Theα-L-fucosidase(AFU)/α-fetoprotein(AFP)combination was best able to distinguish NBNC-HCC[area under the curve:0.986(95%confidence interval:0.958–0.997),sensitivity:92.6%,specificity:98.9%]from healthy controls in the test cohort.For screening populations at risk of developing HCC(CH and LC),the AFP/AFU combination improved the diagnostic specificity for early-stage HCC[area under the curve:0.776(0.712–0.831),sensitivity:52.5%,specificity:91.6%in the test group].In all-stage HBV-HCC and HCV-HCC,AFU was also the best candidate biomarker combined with AFP[area under the curve:0.835(0.784–0.877),sensitivity 69.1%,specificity:87.4%in the test group].All results were verified in the validation group.Conclusions:The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients. | Dongming Liu Yi Luo Lu Chen Liwei Chen Duo Zuo Yueguo Li Xiaofang Zhang Jing Wu Qing Xi Guangtao Li Lisha Qi Xiaofen Yue Xiehua Zhang Zhuoyu Sun Ning Zhang Tianqiang Song Wei Lu Hua Guo | 2021 | Cancer Biology & Medicine2021，18，1： | 10 |
| 2 | Modified Blumgart anastomosis without pancreatic duct-to-jejunum mucosa anastomosis for pancreatoduodenectomy:a feasible and safe novel technique显示文摘Objective:This study proposed a modified Blumgart anastomosis(m-BA)that uses a firm ligation of the main pancreatic duct with a supporting tube to replace the pancreatic duct-to-jejunum mucosa anastomosis,with the aim of simplifying the complicated steps of the conventional BA(c-BA).Thus,we observe if a difference in the risk of postoperative pancreatic fistula(POPF)exists between the two methods.Methods:The m-BA anastomosis method has been used since 2010.From October 2011 to October 2015,147 patients who underwent pancreatoduodenectomy(PD)using BA in Tianjin Medical University Cancer Institute and Hospital were enrolled in this study.According to the type of pancreatojejunostomy(PJ),50 patients underwent m-BA and 97 received c-BA.The two patient cohorts were compared prospectively to some extent but not randomized,and the evaluated variables were operation time,the incidence rate of POPF,and other perioperative complications.Results:The operation time showed no significant difference(P>0.05)between the two groups,but the time of duct-to-mucosa anastomosis in the m-BA group was much shorter than that in the c-BA group(P<0.001).The incidence rate of clinically relevant POPF was 12.0%(6/50)in the modified group and 10.3%(10/97)in the conventional group(P>0.05),which means that the modified anastomosis method did not cause additional pancreatic leakage.The mean length of postoperative hospital stay of the m-BA group was 23 days,and that of the c-BA group was 22 days(P>0.05).Conclusions:Compared with the conventional BA,we suggest that the modified BA is a feasible,safe,and effective operation method for P J of PD with no sacrifice of surgical quality.In the multivariate analysis,we also found that body mass | Xiaoqing Wang Yang Bai Mangmang Cui Qingxiang Zhang Wei Zhang Feng Fang Tianqiang Song | 2018 | Cancer Biology & Medicine2018，15，1： | 6 |
| 3 | Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)显示文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC. | Hui-Chuan Sun Jian Zhou Zheng Wang Xiufeng Liu Qing Xie Weidong Jia Ming Zhao Xinyu Bi Gong Li Xueli Bai Yuan Ji Li Xu Xiao-Dong Zhu Dousheng Bai Yajin Chen Yongjun Chen Chaoliu Dai Rongping Guo Wenzhi Guo Chunyi Hao Tao Huang Zhiyong Huang Deyu Li Gang Li Tao Li Xiangcheng Li Guangming Li Xiao Liang Jingfeng Liu Fubao Liu Shichun Lu Zheng Lu Weifu Lv Yilei Mao Guoliang Shao Yinghong Shi Tianqiang Song Guang Tan Yunqiang Tang Kaishan Tao Chidan Wan Guangyi Wang Lu Wang Shunxiang Wang Tianfu Wen Baocai Xing Bangde Xiang Sheng Yan Dinghua Yang Guowen Yin Tao Yin Zhenyu Yin Zhengping Yu Bixiang Zhang Jialin Zhang Shuijun Zhang Ti Zhang Yamin Zhang Yubao Zhang Aibin Zhang Haitao Zhao Ledu Zhou Wu Zhang Zhenyu Zhu Shukui Qin Feng Shen Xiujun Cai Gaojun Teng Jianqiang Cai Minshan Chen Qiang Li Lianxin Liu Weilin Wang Tingbo Liang Jiahong Dong Xiaoping Chen Xuehao Wang Shusen Zheng Jia Fan 无 | 2022 | Hepatobiliary Surgery and Nutrition2022，11，2： | 4 |
| 4 | Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma显示文摘Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was discussed.Methods: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by WB.Results: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated markers.Conclusions: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and invasion.Our study also suggests that POSTN may serve as a therapeutic biomarker in HB patients. | Lu Chen Xiangdong Tian Wenchen Gong Bo Sun Guangtao Li Dongming Liu Piao Guo Yuchao He Ziye Chen Yuren Xia Tianqiang Song Hua Guo | 2019 | Cancer Biology & Medicine2019，16，1： | 3 |
| 5 | Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition显示文摘Chemotherapy,as one of the most commonly used treatment modalities for cancer therapy,provides limited benefits to hepatoma patients,owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma.Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA-miR-122 for enhancing chemo-therapeutic efficacy in hepatoma.Herein,a cyclodextrin-cored star copolymer nanoparticle system(sCDP/DOX/miR-122)is constructed to co-deliver miR-122 with doxorubicin(DOX)for hepatoma therapy.In this nanosystem,miR-122 is condensed by the outer cationic poly(2-(dimethylamino)ethyl methacrylate)chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities,endowing a sequential release manner of miR-122 and DOX.The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity,but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression,which realizes synergistic performance on cell inhibition.Moreover,sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone,indicating its great promising in hepatoma therapy. | Qingqing Xiong Yang Bai Run Shi Jian Wang Weiguo Xu Mingming Zhang Tianqiang Song | 2021 | Bioactive Materials2021，6，11： | 2 |
| 6 | Multimarker Detection of MAGE-1,MAGE-3 and AFP mRNAs by a Real-time Quantitative PCR Assay:a Possible Predictor of Hematogenous Micrometastasis of Hepatocellular Carcinoma显示文摘OBJECTIVE To explore the relationship between multimarker detection of MAGE-1,MAGE-3 and AFP mRNAs in the peripheral blood of patients with hepatocellular carcinoma and micrometastasis using a realtime quantitative-PCR(real-time Q-PCR)assay. METHODS Peripheral blood samples were obtained from control subjects and 86 patients with hepatocellular carcinoma (HCC).Real-time Q-PCR was used to detect MAGE-1,MAGE-3, and AFP mRNAs in the blood cells. RESULTS In 86 tumor specimens,the positivity for MAGE-1, MAGE-3,and AFP genes was respectively 34.9%(30/86),60.5% (52/86)and 69.8%(60/86).All specimens expressed at least one marker.MAGE-1,MAGE-3,and AFP transcripts were detected respectively in 12(14.0%),18(20.1%)and 29(33.7%)of the 86 blood specimens from hepatocellular carcinoma patients,while 45 specimens(52.3%)were positive for at least one marker.In addition,MAGE-1,MAGE-3 and AFP gene transcripts were not detected in any peripheral blood specimens from 25 chronic liver disease patients and 28 normal healthy volunteers.The positive rate correlated with the TNM clinical stages,extrahepatic metastasis and portal vein carcinothrombosis(P<0.05).No correlation was found between tumor size,tumor number, differentiation,serum a-fetoprotein(AFP)and the positive rate. CONCLUSION Our results indicate that a multimarker real- time Q-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a hepatocyte-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients with better sensitivity and specificity. | Yuqing Zhang Qiang Li Ning Liu Tianqiang Song Rende Guo Lingxin Meng Xishan Hao | 2008 | Chinese Journal of Clinical Oncology2008，5，2： | 2 |
| 7 | Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy显示文摘Recent studies have demonstrated the potential of natural killer(NK)cells in immunotherapy to treat multiple types of cancer.NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex.The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers.NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy.The effector role of these cells is reliant on the balance of inhibitory and activating signals.Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation.Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment;this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers.Accordingly,this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function,as well as their potential application in tumor immunotherapy. | Yuqing Cao Xiaoyu Wang Tianqiang Jin Yu Tian Chaoliu Dai Crystal Widarma Rui Song Feng Xu | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 8 | Adjuvant therapy for intrahepatic carcinoma after surgical resection:chemotherapy and future perspectives显示文摘Intrahepatic cholangiocarcinoma is a highly aggressive and malignant liver cancer.The main reason for its poor prognosis is the low opportunity of surgery and the high rates of postoperative recurrence and metastasis.Thus,reducing postoperative recurrence and metastasis rate is the key to improving prognosis.Although some retrospective studies have attested to the value of adjuvant therapy in patients with R1 resection or N1/T3/T4 intrahepatic cholangiocarcinoma(1),no recommended standard yet exists in intrahepatic cholangiocarcinoma primarily because the only 2 completed phase III clinical trials,the PRODIGE 12-ACCORD 18 trial(2)and the BILCAP trial(3),failed to achieve survival benefit in the chemotherapy arm in the adjuvant setting.However,one of the possible reasons for the negative results of the 2 studies is that patients with R1/N1/T3/T4 were not differentiated.One randomized phase III trials(JCOG1202,ASCOT)of adjuvant S-1 therapy vs.observation alone in resected biliary tract cancer(4)and one trial(ACTICCA-1 trial)of adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma(5)are ongoing and awaiting future results. | Wei Zhang Tianqiang Song | 2021 | Hepatobiliary Surgery and Nutrition2021，10，6： | 0 |
| 9 | Five-CpG-based prognostic signature for predicting survival in hepatocellular carcinoma patients显示文摘Objective:Hepatocellular carcinoma(HCC)is a common malignancy associated with high morbidity and mortality rates worldwide.Early diagnosis plays an important role in the improvement of HCC prognosis.Methods:In this study,we conducted a comprehensive analysis of HCC DNA methylation and gene expression datasets in The Cancer Genome Atlas(TCGA),to identify a prognostic signature for HCC diagnosis and survival prediction.First,we identified differential methylation CpG(dmCpG)sites in HCC samples and compared them with those in adjacent normal liver tissues;this was followed by univariate analysis and Sure Independence Screening(SIS)in the training set.The robustness of the identified prognostic signature was evaluated using the testing set.To explore the biological processes involved in HCC progression,we also performed functional enrichment analysis for overlapping genes between genes containing dmCpG sites(DMGs)and differential expression genes(DEGs)in HCC patients,using data from the Database for Annotation,Visualization,and Integrated Discovery(DAVID).Results:As a result,we identified five CpG sites that were significantly associated with HCC survival through univariate analysis and SIS.Univariate analysis of clinical characteristics identified age and risk factors(including alcohol consumption and smoking)as independent factors that indicated HCC survival.Multivariate analysis indicated that the integrated prognostic signature(weighted combination of the five CpG sites)that took age and risk factors into consideration resulted in more accurate survival prediction.Conclusions:This study provides a novel signature for predicting HCC survival,and should be helpful for early HCC diagnosis and personalized treatment. | Feng Fang Xiaoqing Wang Tianqiang Song | 2018 | Cancer Biology & Medicine2018，15，4： | 0 |
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