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Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

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World Journal of Gastroenterology 2024年第11期30卷 1533-1544页

作者： Li-Min Yang Hong-Juan Wang Shan-Lin Li Guan-Hua Gan Wen-Wen Deng Yong-Sheng Chang Lian-Feng Zhang Department of Gastroenterology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Gastroenterology Zhoukou Central Hospital of Henan ProvinceZhoukou 466000Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453000Henan ProvinceChina

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in treatment.AIM To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this condition.METHODS Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment regimen.The research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received RFA.The short-term efficacy of both the research and control groups was observed.Liver function and portal hypertension were compared before and after treatment.Alpha-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after treatment.The occurrence of adverse reactions in both groups was observed.The 3-year survival rate was compared between the two groups.Basic data were compared between the survival and non-surviving groups.To identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was employed.RESULTS When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both groups.The degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly greater than that in the control group(P<0.05).The 1-

关键词： Radiofrequency ablation sorafenib Liver cancer Portal hypertension Efficacy Prognosis analysis

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sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

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World Journal of Hepatology 2024年第1期16卷 91-102页

作者： Hong-Jie Yang Bin Ye Jia-Xu Liao Lei Lei Kai Chen Department of Radiology The Sixth People's Hospital of ChengduChengdu 610000Sichuan ProvinceChina Department of Oncology The Sixth People's Hospital of ChengduChengdu 610000Sichuan ProvinceChina Department of Pharmacy The Affiliated Taizhou People's Hospital of Nanjing Medical UniversityTaizhou 225300Jiangsu ProvinceChina

BACKGROUND Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma(HCC),the dismal overall prognosis still envelops HCC patients.Several comparative trials have been conducted to study whether transarterial chemoembolization(TACE)could improve clinical outcomes in patients receiving sorafenib for advanced HCC;however,the findings have been inconsistent.AIM To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC,by performing a systematic review and metaanalysis.METHODS This study was conducted following the PRISMA statement.A systematic literature search was conducted using the Cochrane Library,Embase,PubMed,and Web of Science databases.Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone.Data synthesis and meta-analysis were conducted using Review Manager software.RESULTS The present study included 2780 patients from five comparative clinical trials(1 was randomized control trial and 4 were retrospective studies).It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival(OS),with a combined hazard ratio(HR)of 0.65[95%confidence interval(95%CI):0.46–0.93,P=0.02,n=2780].Consistently,progression free survival(PFS)and time to progression(TTP)differed significantly between the sorafenib plus TACE arm and sorafenib arm(PFS:HR=0.62,95%CI:0.40–0.96,P=0.03,n=443;TTP:HR=0.73,95%CI:0.64-0.83,Psorafenib with TACE has superior efficacy to sorafenib monotherapy,as evidenced by prolonged OS,PFS,and TTP,as well as increased DCR.Additional high-quality trials are essenti

关键词： Hepatocellular carcinoma sorafenib Transarterial chemoembolization Systematic review Meta-analysis

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Luteolin alleviates sorafenib-induced ferroptosis of BRL-3A cells through modulation of the Nrf2/GPX4 signaling pathway

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Traditional Medicine Research 2024年第10期9卷 1-9页

作者： Bo-Wen Zhang Di Yang Jin-Tao Li Mei-Hao Peng Jia-Qing Liao Qi Zhao Yi-Xi Yang Qiu-Xia Lu Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant Chengdu UniversityChengdu 610106China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China School of Pharmacy Chengdu UniversityChengdu 610106China

Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.

关键词： luteolin sorafenib liver injury ferroptosis Nrf2/GPX4

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FGF21 increases the sensitivity of hepatocellular carcinoma to sorafenib under hypoxia

Malignancy Spectrum

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Malignancy Spectrum 2024年第2期1卷 99-112页

作者： Ting Zhang Huiling Shi Shihui Zhang Qin Zhu Mengyuan Qiu Ashleigh T.Chitakunye Hanyu Hong Liaoxin Luo Yujing Li Qiuyu Sun Xiaokun Li Lin Cai Department of Biopharmaceuticals School of Pharmaceutics SciencesWenzhou Medical UniversityWenzhouZhejiangChina

Background:Hepatocellular carcinoma(HCC)is a common disease in human history and one of the main causes of cancer-related death.Insufficient oxygen supply in the tumor microenvironment forces cancer cells to survive in a mild hypoxia environment.Fibroblast growth factor 21(FGF21),a member of the FGF family,has become the focus of public attention due to its outstanding achievements in diabetes and lipid lowering.However,the mechanism of FGF21 in HCC remains unclear.Objective:The aims of this study were to clarify whether or not FGF21 could increase the sensitivity of HCC to sorafenib(SORA)under hypoxia and explore the possible mechanism.Methods:In this study,by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide cell viability test,plate clone formation test,western blot analysis,Hoechst/propidium iodide double staining experiment,flow cytometry,quantitative reverse transcription polymerase chain reaction,and subcutaneous tumor transplantation in mice,we studied the effects of recombinant human FGF21 combined with SORA on hepatoma cells in vitro and in vivo.FGF21 could enhance the phosphorylation of mothers against decapentaplegic homolog 3(Smad3)under anaerobic conditions.When combined with SORA,FGF21 could increase the sensitivity of hepatoma cells to SORA and inhibit the growth and migration of hepatoma cells.Results:FGF21 may increase the sensitivity of HCC to SORA by enhancing the phosphorylation of Smad3 through the phosphatidylinositol 3-kinase/protein kinase B pathway under hypoxia.Conclusion:Our study suggested the possibility of combination therapy for SORA and FGF21 on HCC.

关键词： FGF21 sorafenib drug resistance hypoxia Smad3

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The flavonoids from Pentorum chinense Pursh.mediates ferroptosis to alleviate sorafenib-induced liver injury in BRL-3A cells

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Traditional Medicine Research 2024年第2期9卷 18-26页

作者： Di Yang Bo-Wen Zhang Shan Lei Jin-Tao Li Mei-Hao Peng Jia-Qing Liao Xue Tang Qi Zhao Qiu-Xia Lu Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant Chengdu UniversityChengdu 610106China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China School of Pharmacy Chengdu UniversityChengdu 610106China Chengdu Analytical Applications Center Shimadzu(China)Co.Ltd.Chengdu 610023China

Background:Drug-induced liver damage is a severe medical issue that affects people all over the world.sorafenib has some side effects that cause liver injury.A dietary medicinal plant called Penthorum chinense Pursh.(PCP)has hepatoprotective properties.There are currently few reports on PCP’s protective impact and mechanism against sorafenib-induced liver injury.Methods:To create a liver injury model,sorafenib was administered to BRL-3A cells.Cell viability assays,immunofluorescence tests,Western blotting,real-time quantitative PCR,and high-content imaging systems were utilized to examine PCP’s effect and mechanism.Results:In this study,PCP treatment mitigated the liver damage caused by sorafenib by enhancing cell survival,lowering lipid reactive oxygen species and malondialdehyde levels,and elevating glutathione levels.In addition,PCP can enhance the protein expression of cystine/glutamate transporter xCT and glutathione peroxidase 4,reduce iron content and alleviate mitochondrial toxicity.Further mechanism studies revealed that PCP inhibited ferroptosis by promoting the production of nuclear factor E2-related factor 2 nuclear translocation and subsequently affecting target genes(HO-1 and NQO1).Conclusion:Together,PCP regulates the nuclear factor E2-related factor 2 pathway,which helps to lessen ferroptosis brought on by sorafenib.

关键词： sorafenib Pentorum chinense Pursh. ferroptosis oxidative stress Nrf2

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Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen Qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma sorafenib

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Multidisciplinary comprehensive treatment of massive hepatocellular carcinoma with hemorrhage:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2225-2232页

作者： Xian-Shuai Kou Fan-Fan Li Yun Meng Jian-Ming Zhao Sheng-Fen Liu Lan Zhang The First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina Department of Thoracic Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Department of Orthopedics Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC),a major contributor to cancer-related deaths,is particularly prevalent in Asia,largely due to hepatitis B virus infection.Its prognosis is generally poor.This case report contributes to the medical literature by detailing a unique approach in treating a large HCC through multidisciplinary collaboration,particularly in patients with massive HCC complicated by ruptured bleeding,a scenario not extensively documented previously.CASE SUMMARY The patient presented with large HCC complicated by intratumoral bleeding.Treatment involved a multidisciplinary approach,providing individualized care.The strategy included drug-eluting bead transarterial chemoembolization,sorafenib-targeted therapy,laparoscopic partial hepatectomy,and standardized sintilimab monoclonal antibody therapy.Six months after treatment,the patient achieved complete radiological remission,with significant symptom relief.Imaging studies showed no lesions or recurrence,and clinical assessments confirmed complete remission.This report is notable as possibly the first docu-mented case of successfully treating such complex HCC conditions through integrated multidisciplinary efforts,offering new insights and a reference for future similar cases.CONCLUSION This study demonstrated effective multidisciplinary treatment for massive HCC with intratumoral bleeding,providing insights for future similar cases.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Sintilimab sorafenib Translational therapy Multidisciplinary team Case report

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Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 554-570页

作者： Yin-Xuan Pei Chen-Guang Su Zheng Liao Wei-Wei Li Zi-Xiang Wang Jin-Long Liu Department of Hepatobiliary Surgery The Affiliated Hospital of Chengde Medical UniversityChengde 067000Hebei ProvinceChina

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor or

关键词： Hepatocellular carcinoma Adjuvant therapy Network meta-analysis Transarterial chemoembolization Hepatic artery infusion chemotherapy Radiotherapy sorafenib

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A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

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Chinese Chemical Letters 2024年第2期35卷 295-299页

作者： Qi Fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun Yang Lei Wang Dandan Tian Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450001China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Translational Medical Center of Huaihe Hospital Henan UniversityKaifeng 475004China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关键词： Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter sorafenib Photodynamic therapy

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Comprehensive treatment of von Hippel-Lindau disease:A case report

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Cancer Innovation 2024年第2期3卷 63-67页

作者： Xuesong Li Zheng Mo Zhuo Yu School of Clinical Medicine Tsinghua UniversityBeijingChina Department of Oncology Beijing Tsinghua Changgung HospitalBeijingChina

von Hippel-Lindau(VHL)disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular,as well as cysts in other organs.A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease.Herein,we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma(HB)and clear cell renal cell carcinoma(ccRCC).Four years after the resection of the right kidney,a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed.This patient was started on sorafenib(800 mg,daily)and tislelizumab(200 mg per 3 weeks).After 6 months of treatment,the size of renal cell carcinoma was dramatically reduced and renal function improved.More importantly,she achieved partial response during the whole treatment.Microscopically,intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed.Neurologic symptoms such as numbness and pain were remarkably alleviated.Additionally,tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine,respectively.In short,comprehensive treatment strategies may benefit patients with VHL disease,especially with HB and ccRCC.

关键词： sorafenib surgery tislelizumab treatment von Hippel-Lindau disease

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