Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Research Progress of circRNAs during Epithelial- Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.

Short-term efficacy assessment of transarterial chemoembolization combined with radioactive iodine therapy in primary hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)is an effective treatment for primary hepatocellular carcinoma(PHC).Radioactive iodine therapy has been used in the treatment of advanced PHC,especially in patients with portal vein tumor thrombosis.However,data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce.AIM To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography(CT).METHODS For this study,98 advanced PHC patients were recruited and divided randomly into the study and control groups.Patients in the study group were treated with TACE combined radioactive iodine implantation therapy.Patients in the control group were treated with only TACE.The tumor lesion length,clinical effect,serum alpha-fetoprotein(AFP)and CT perfusion parameters were compared before and after therapy,and statistical analysis was performed.RESULTS There was no significant difference in tumor length and serum AFP between the study and control groups(P>0.05)before treatment.However,the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy.After 3 mo of treatment,the complete and partial remission rate of the study group was 93.88%,which was significantly higher than the control group(77.55%)(P<0.05).Before treatment,there were no significant differences between the two groups on the perfusion CT variables,including the lesion blood volume,permeability surface,blood flow,hepatic artery flow and mean transit time(P>0.05).After 3 mo of treatment,all perfusion CT variables were lower in the study group compared to the control group(P<0.05).The survival time of patients in the study group was 22 mo compared to 18 mo in the control group,which was significantly different[log rank(Mantel-Cox)=4.318,P=0.038].CONCLUSION TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions,thereby improving the clinical efficacy and prolonging the survival time of patients.

Effects of kanglaite capsules combined with transcatheter arterial chemoembolization （TACE） on patients with mid or late-stage primary hepatocellular carcinoma （HCC）

观察囊与 transcatheter 相结合的 kanglaite (KLT ) 的临床的效果的目的动脉的 chemoembolization (不作声) 在与中间或迟了阶段的主要肝细胞癌(HCC ) 对待病人。65 个盒子随机被划分成 2 个组，的方法在联合组的 32 个病人接受了 KLT 囊 + 的治疗不作声，在控制组的 33 个病人被对待与独自不作声。客观反应率(RR ) ，浆液高山哈 fetoprotein (法新社) ，外部血 T 淋巴细胞亚群(T-LS ) ，生命(QOL ) 的质量，前进(TTP ) 的时间和不利反应在 2 之间被遵守并且比较组。客观反应评估的结果和浆液高山哈 fetoprotein 层次没有在二个组之间的有效差量(P 】 0.05 ) 。联合组是优异的在生命(QOL ) 的质量控制组，前进(TTP ) 的时间，外部血 T 淋巴细胞亚群(CD3+ ， CD4+ ， CD4+&#8726;CD8 比率) 并且肝不利反应，与有效差量(P 【 0.05 ) 。结论 KLT 囊与结合了不作声是到对待的一个有效方法失去了外科的治疗的机会的主要肝细胞癌(HCC ) 病人。

Surgical treatment for recurrent hepatocellular carcinoma:Current status and challenges

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic cholangiocarcinoma(representing 10%-15%of cases),and other rare types.The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years;however,high tumor recurrence rates continue to limit long-term survival,even after radical surgical resection(exceeding 50%recurrence).For resectable recurrent liver cancer,surgical removal[either salvage liver transplantation(SLT)or repeat hepatic resection]remains the most effective therapy that is potentially curative for recurrent HCC.Thus,here,we introduce surgical treatment for recurrent HCC.Areas Covered:A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022.Expert commentary:In general,long-term survival after the reresection of recurrent liver cancer is usually beneficial.SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients;however,SLT is constrained by the supply of liver grafts.SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival.When considering the similar overall survival rate and the current situation of donor shortages,repeat liver resection remains an important option for recurrent HCC.

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Combination of serum tumor markers dickkopf-1,DCP and AFP for the diagnosis of primary hepatocellular carcinoma

Objective:To evaluate the detection accuracy of the biomarkers dickkopf-1,DCP and AFP as a serum biomarker panel by comparing the sensitivity of the panel with those of the individual biomarkers.Methods:The study was composed of three groups,one with HCC patients,one with non-HCC liver diseases and one with healthy controls.Serum AFP was measured using a chemiluminescence assay and serum dickkopf-1 and DCP were measured with ELISA.The sensitivity and specificity of the biomarkers were analyzed as single parameters and as a serum panel.Results:The HCC group showed higher levels of dickkopf-1,DCP and AFP than the other two groups(P<0.05).Dickkopf-1 showed better sensitivity(73.26%vx.58.13%.P<0.05) and better specificity(44.00%vs.29.00%,P>0.05) than AFP.DCP also had better sensitivity(74.42%vs.58.13%.P<0.05) than AFP,but their specificity was similar(30.00%vs.29.00%.P>0.05).The combination of the biomarkers as a scrum panel produced much better sensitivity(93.02%) and specificity(78.00%) than each of the markers individually(P<0.05).Conclusion:The combination of AFP.DCP and dickkopf-1 as a biomarker panel can significantly improve the detection power with much higher sensitivity and specificity for HCC than any of the biomarkers alone.The tests are convenient and inexpensive,and may serve as a valuable addition to current options for the diagnosis of HCC.

Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients:Incidence and risk factors

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma(HCC) in Chinese patients with primary biliary cirrhosis(PBC).METHODS: We reviewed the data of 52 PB Cassociated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13%(52/1255) and was significantly higher in the males(9.52%) than in the females(3.31%). Among the 52 PBC patients with HCC, 55.76%(29/52) were diagnosed with HCC and PBC simultaneously, and 5.76%(3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCCwere more likely than the females to have undergone blood transfusion(18.75% vs 8.33%, P = 0.043), consumed alcohol(31.25% vs 8.33%, P = 0.010), smoked(31.25% vs 8.33%, P = 0.010), had a family history of malignancy(25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase(P < 0.05). Conditional logistic regression analysis revealed that body mass index(BMI) ≥ 25 [adjusted odds ratio(AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake(AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

Diagnostic value of imaging examinations in patients with primary hepatocellular carcinoma

Primary hepatocellular carcinoma(PHC) includes hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other pathological types and is characterized by rapid progression. Most of the clinical diagnoses are made at late stage or when distant metastasis occurs, increasing the difficulty of treatment and resulting in a poor prognosis. Therefore, the early diagnosis of PHC plays an important role in timely treatment and the improvement of prognosis. The gold standard for the diagnosis of primary liver cancer is liver biopsy, but it has limitations as an invasive examination. Presently, imaging has become the first choice for the diagnosis of liver cancer. We here summarize the new methods and techniques of imaging in diagnosis and evaluation of primary liver cancer in recent years, including ultrasonography, computed tomography perfusion imaging, diffusion-weighted imaging technology-voxel incoherent motion, diffusion tensor imaging, iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantification, dynamic enhanced magnetic resonance imaging and hepatocyte-specific contrast medium imaging. Imaging diagnosis can not only evaluate the degree of differentiation, blood supply and perfusion, and invasiveness of the lesion, but also predict the prognosis, evaluate liver function, andprovide references for clinical diagnosis and treatment.

Emergency caudate lobectomy for ruptured hepatocellular carcinoma with multiple primary cancers

We report a case of metachronous multiple primary malignancies involving both rectum and liver with colonic metastasis from hepatocellular carcinoma(HCC) through hematogenous pathway.A 72-year-old woman was admitted to the emergency department with right upper abdominal pain for 4 h.Considering her surgical history of Mile's procedure plus liver resection for rectal cancer with liver metastasis three years ago and the finding of urgent computed tomography scan on admission,the preoperative diagnosis was spontaneous rupture of rectal liver metastasis located in caudate lobe and colonic metastasis from rectal cancer. The patient underwent an emergency isolated caudate lobectomy at a hemorrhagic shock status.Pathology reported a primary HCC in the caudate lobe and colonic metastasis of HCC with tumor embolus in the surrounding vessels of the intestine.No regional lymph node involvement was found.It is hypothesized that HCC may disseminate hematogenously to the ascending colon,thus making it a rare case.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to in vestigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological pa rameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene am plification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prog nosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patient with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated signifi cantly with tumor size and postoperative survival time o HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P— 0.257), but not related to sex, age, AFP level, HBV infec tion, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was exa mined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 pa tients with aneuploidy (52.4%). No significant relation were observed between the HER-2 oncogene copy, patien sex, tumor size, histopathological grading, clinical stag ing, postoperative relapse and survival time (P >0.05); bu the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P <0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromo- some 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and pro- gression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the re- currence and poor survival in patients with large HCC.

Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: a prospective study

Objective: To observe the clinical efficacy of tran- scatheter arterial chemoembolization (TACE) and TACE+MLT (melatonin) on inoperable advanced primary hepatocellular carcinoma. Methods: From January 1997 to January 1998, one hundred patients with inoperable advanced primary hepatocellular carcinoma were treated separately by TACE (50) and TACE+MLT (20 mg/d at 8:00 PM orally, 7 days before TACE) (50). Results: The effective rates (WHO standards) of TACE and TACE+MLT were 16% and 28% respec- tively (P<0.05). After TACE or TACE+MLT, the resection rate at two-stage of TACE was 4% or 14% (P<0. 01). The 0.5-, 1- and 2-year survival rates in the TACE group were 82%, 54% and 26% respectively; in the TACE+MLT group 100%, 68% and 40% respectively. The results were significantly better in the TACE+MLT group than in the TACE group. MLT could protect liver function from the damage caused by TACE. The IL-2 levels of all pa- tients significantly increased, whereas sIL-2R expres- sions decreased after TACE+MLT as compared with the TACE group (P<0.01). Conclusions: With definite protection and treatment effect on the liver function damage caused by TACE, MLT can enhance the immunological activities of pa- tients. It also can improve the effect of TACE by in- creasing the survival and resection rate after two- stage operation.

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

Primary biliary cholangitis metachronously complicated with combined hepatocellular carcinoma-cholangiocellular carcinoma and hepatocellular carcinoma

Primary biliary cholangitis(PBC) is a progressive cholestatic liver disease characterized by the presence of highly specific antimitochondrial antibodies, portal inflammation and lymphocyte-dominated destruction of the intrahepatic bile ducts, which leads to cirrhosis. While its pathogenesis remains unclear, PBC that shows histological progression to fibrosis carries a high risk of carcinogenesis; the same is true of viral liver diseases. In patients with PBC, the development of hepatocellular carcinoma(HCC) is rare; the development of combined hepatocellular carcinoma and cholangiocellular carcinoma(c HCC-CCC) is extraordinary. Herein, we report a rare case of PBC metachronously complicated by c HCC-CCC and HCC, which, to the best of our knowledge, has never been reported. We present a case report of a 74-year-old Japanese woman who was diagnosed as PBC in her 40's by using blood tests and was admitted to our department for further management of an asymptomatic liver mass. She had a tumor of 15 mm in size in segment 8 of the liver and underwent a partial resection of the liver. Subsequent pathological findings resulted in the diagnosis of c HCC-CCC, arising from stage 3 PBC. One year after the initial hepatectomy, a second tumor of 10 mm in diameter was found in segment 5 of the liver; a partial resection of the liver was performed. Subsequent pathological findings led to HCC diagnosis. The component of HCC in the initial tumor displayed a trabecular growth pattern while the second HCC showed a pseudoglandular growth pattern, suggesting that metachronous tumors that arise from PBC are multicentric.

Short-term Outcomes of Laparoscopic vs.Open Hepatectomy for Primary Hepatocellular Carcinoma:A Prospective Comparative Study

Laparoscopic hepatectomy(LH)is a newly developed technique associated with advantages as open surgery,but the study on outcome of liver function recovery was scarce.This preliminary report was aimed to comparatively assess the short?term outcomes between LH and open hepatectomy(OH)for primary hepatocellular carcinoma(PHC).This study retrospectively analyzed the demographic data and short-term outcomes of 81 patients who underwent LH or OH for the primary treatment of PHC between Oct.2017 and May 2018 at Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(China).A total of 81 PHC patients who received major liver resection were enrolled.There were 38(47%)patients in the LH group and 43(53%)patients in the OH group.The operative time was significantly longer(373.53±173.38 vs.225.43±55.08,P<0.01),and hospital stay(17.34±5.93 vs.21.70±6.89,P=0.003),exhaust time(2.32±0.62 vs.3.07±0.59,P<0.01)and defecation time(2.92±0.78 vs.3.63±0.58,P<0.01)were significantly shorter in LH group than in OH group.The recovery of liver function was significantly faster in LH group,including higher serum albumin(P=0.002),higher ratio of albumin/globulin(P=0.029)and lower direct bilirubin(P=0.001)than in OH group.It is suggested that LH can serve as a fast recovery and cheap surgical procedure in the treatment of PHC,which is safe and feasible.

Thirty-one patients with primary hepatocellular carcinoma survived for more than 5 years after hepatectomy

Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had sur- vived for more than 5 years were compared with 56 patients who had survived for less than 5 years. Results: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, pre- sence of cirrhosis and tumor size were important fac- tors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. Conclusions: Early detection of tumor and radical re- section are of value in raising the 5-year survival rate. Much remains to be investigated about the rela- tionship between safe margin distance and prognosis of patients with PHC.

Small-duct primary sclerosing cholangitis with hepatocellular carcinoma requiring liver transplantation

BACKGROUND:Primary sclerosing cholangitis(PSC)is a chronic progressive cholestatic liver disease,which usually affects young adults and is diagnosed by cholangiography.On a few occasions,the disease either starts in or exclusively involves the small intrahepatic bile ducts,referred to as small-duct PSC. METHODS:A 31-year-old man presented with severe hematemesis secondary to liver cirrhosis.Over a course of 8 years,his liver decompensated and required an orthotopic liver transplantation. In this report we discuss his disease presentation,course of management,and the post-transplantation course of manage- ment,and review the morphologic diagnosis,and differential diagnosis of the disease with large-duct type and other diseases that involve small intrahepatic bile ducts. RESULTS:The patient’s explanted liver showed changes of PSC affecting only the small-and medium-sized bile ducts in addition to three incidental nodules of hepatocellular carcinoma. CONCLUSIONS:Small-duct PSC has a substantially better prognosis than the large-duct type,with less chance of developing cirrhosis and an equal risk for developing hepato- cellular carcinoma,but no increased risk for developing cholangiocarcinoma.Treatment seems to help relieve the symptoms but not necessarily improve survival.Liver transplantation remains the ultimate cure.

INTS10对HCC细胞周期、凋亡、生长和迁移能力的影响

为了探究整合因子复合物亚基10(integrator complex subunits 10,INTS10)对人肝细胞癌(hepatocellular carcinoma,HCC)细胞周期、凋亡、生长和迁移能力的影响及其潜在的分子作用机制,利用慢病毒感染法获得稳定过表达或敲低INTS10的HCC细胞系,采用qRT-PCR和Western blotting检测INTS10 mRNA和蛋白表达水平,接着采用CCK-8法、克隆形成和BrdU实验检测细胞生长情况,采用Transwell小室实验检测细胞迁移能力,采用流式分析术检测细胞的周期和凋亡.结果显示:过表达INTS10可显著抑制HCC细胞的凋亡、生长和迁移能力,促进G1期细胞数量的增加,而敲低INTS10则呈现相反的表型.通过通路富集分析发现,周期相关通路被显著富集,过表达INTS10后,CDC25A和CDK4的mRNA和蛋白质水平显著减少,而CDKN1A的水平显著增加,敲低INTS10则呈现相反趋势.综上,本研究初步揭示了INTS10在HCC细胞中可能通过影响G1/S期相关蛋白质的表达而发挥抑癌基因的功能,为下一步更为深入的功能和机制研究提供了基础.