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Improving the Conversion Success Rate of Hepatocellular Carcinoma: Focus on the Use of Combination Therapy with a High Objective Response Rate

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 298-304页

作者： Qi-Feng Chen Song Chen Minshan Chen Ning Lyu Ming Zhao Department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina State Key Laboratory of Oncology in South China GuangzhouGuangdongChina Department of Liver Surgery Sun Yat-sen University Cancer CenterGuangzhouGuangdongChina

The high mortality rate in hepatocellular carcinoma(HCC)is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage,with surgical treatment options *** therapy,which involves both locoregional and systemic treatments,has the potential to downstage tumors in selected patients with initially unresectable HCC,thereby making surgical treatment a possibility and potentially increasing long-term *** optimize the conversion rate,it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative *** this review article,we summarize the clinical experience and evidence for conversion therapy in patients with‘potentially resectable’HCC from four perspectives:1)defining the target population for conversion therapy,2)selecting the appropriate conversion strategy,placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate,3)determining the timing and urgency of surgical resection,4)promoting the adoption of a multidisciplinary team *** authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC,the success rate of HCC conversion therapy will increase,and the overall survival of HCC patients will be prolonged.

关键词： Hepatocellular carcinoma Conversion therapy Conversion rate Targeted population Combination therapy

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Recent Advances in Pd-Catalyzed Reactions Involving the “On-Water” Mechanism

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Chinese Journal of Chemistry 2024年第5期42卷 533-542页

作者： Dong Wei Guo-Qiang Lin State Key Laboratory of Systems Medicine for cancer Shanghai Cancer InstituteShanghai Key Laboratory of Systems Regulation and Clinical Translation for CancerRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai200127 China State Key Laboratory of Chemical biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032 China

As the chemical industry grapples with the need for more eco-friendly practices,the use of water as a reaction medium is gaining attraction in organic *** mini-review delves into Pd-catalyzed reactions that utilize the "on-water" mechanism,spanning from 2019 to late *** reactions are neatly categorized into several types: (A) Catalytic C—H activations,(B) Mizoroki- Heck-type reactions,(C) Suzuki-Miyaura reactions,and (D) Cyclization *** showcasing the potential of water as a sustainable reaction medium for organic transformations,these reactions leave no doubt about the importance of embracing eco-friendly practices in the chemical *** Scientists In 1980,a seminal work by Breslow et *** an acceleration of reaction rate in the Diels-Alder *** and co-workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water,as opposed to when it was carried out in organic *** term "on-water" was then coined to describe this *** strategy was further expanded to transition-metal catalyzed transformations by Ackermann in ***,Varma and Leazer disclosed a Pd-catalyzed Mizoroki-Heck type arylation of alkenes with diaryliodonium salts “on-water”.The enantioselective version of "on-water" process was not realized until 2014 by the Zhou *** on,the Schaub group described a Pd-catalyzed Suzuki–Miyaura coupling reaction of electron-poor aryl chlorides with water,using only 50 ppm of catalyst *** recently,Liu and Lin extended the "on-water" strategy to Pd-catalyzed double Mizoroki-Heck *** mini-review has focused on Pd-catalyzed reactions involving the “on-water” mechanism.

关键词： Pd-catalyzed “On-water” Green chemistry Aqueous reactions Mechanism Methodology and reactions Mizoroki-Heck reaction Cross-coupling

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Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer:an interim analysis of a phase Ⅲ randomized clinical trial

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cancer Communications 2024年第10期44卷 1214-1227页

作者： Yan Zheng Guanghui Liang Dongfeng Yuan Xianben Liu Yufeng Ba Zimin Qin Sining Shen Zhenxuan Li Haibo Sun Baoxing Liu Quanli Gao Peng Li Zongfei Wang Shilei Liu Jianping Zhu Haoran Wang Haibo Ma Zhenzhen Liu Fei Zhao Jun Zhang He Zhang Daoyuan Wu Jinrong Qu Jie Ma Peng Zhang Wenjie Ma Ming Yan Yongkui Yu Qing Li Jiangong Zhang Wenqun Xing Department of Thoracic Surgery The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Immunotherapy The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Endoscopy The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Pathology The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Radiology The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Biobank The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Strategic Development The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenanP.R.China Department of Statistics LinkDoc Technology Co.LtdBeijingP.R.China Department of cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouP.R.China

Background:In the era of immunotherapy,neoadjuvant immunochemotherapy(NAIC)for the treatment of locally advanced esophageal squamous cell carcinoma(ESCC)is used clinically but lacks of high-level clinical *** study aimed to compare the safety and long-term efficacy of NAIC followed byminimally invasive esophagectomy(MIE)with those of neoadjuvant chemotherapy(NAC)followed by ***:A prospective,single-center,open-label,randomized phase Ⅲ clinical trial was conducted at Henan cancer Hospital,Zhengzhou,*** were randomly assigned to receive either neoadjuvant toripalimab(240mg)plus paclitaxel(175 mg/m^(2))+cisplatin(75 mg/m^(2))(toripalimab group)or paclitaxel+cisplatin alone(chemotherapy group)every 3 weeks for 2 *** surgery,the toripalimab group received toripalimab(240 mg every 3 weeks for up to 6 months).The primary endpoint was event-free survival(EFS).The pathological complete response(pCR)and overall survival(OS)were key secondary *** events(AEs)and quality of life were also ***:Between May 15,2020 and August 13,2021,252 ESCC patients ranging fromT1N1-3M0 to T2-3N0-3M0were enrolled for interim analysis,with 127 in the toripalimab group and 125 in the chemotherapy *** 1-year EFS rate was 77.9%in the toripalimab group compared to 64.3%in the chemotherapy group(hazard ratio[HR]=0.62;95%confidence interval[CI]=0.39 to 1.00;P=0.05).The 1-year OS rates were 94.1%and 83.0%in the toripalimab and chemotherapy groups,respectively(HR=0.48;95%CI=0.24 to 0.97;P=0.037).The patients in the toripalimab group had a higher pCR rate(18.6%vs.4.6%;P=0.001).The rates of postoperative Clavien-Dindo grade Ⅲb or higher morbidity were 9.8%in the toripalimab group and 6.8%in the chemotherapy group,with no significant difference observed(P=0.460).The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups(12.5%versus 12.4%).Conclusions:The interim results of this ongoing trial showed that in resec

关键词： esophageal squamous cell carcinoma minimally invasive esophagectomy neoadjuvant chemotherapy neoadjuvant immunochemotherapy survival

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Supposition of graphene stacks to estimate the contact resistance and conductivity of nanocomposites

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 663-676页

作者： Y.ZARE M.T.MUNIR G.J.WENG K.Y.RHEE Biomaterials and Tissue Engineering Research group Department of Interdisciplinary TechnologiesBreast Cancer Research CenterMotamed Cancer InstituteTehran ***Iran College of Engineering and Technology American University of the Middle EastEgaila 54200Kuwait Department of Mechanical and Aerospace Engineering Rutgers UniversityNew BrunswickNJ 08903U.S.A. Department of Mechanical Engineering(BK21 Four) College of EngineeringKyung Hee UniversityYongin 446701Republic of Korea

In this study,the effects of stacked nanosheets and the surrounding interphase zone on the resistance of the contact region between nanosheets and the tunneling conductivity of samples are evaluated with developed equations superior to those previously *** contact resistance and nanocomposite conductivity are modeled by several influencing factors,including stack properties,interphase depth,tunneling size,and contact *** developed model's accuracy is verified through numerous experimental *** further validate the models and establish correlations between parameters,the effects of all the variables on contact resistance and nanocomposite conductivity are ***,the contact resistance is primarily dependent on the polymer tunnel resistivity,contact area,and tunneling *** dimensions of the graphene nanosheets significantly influence the conductivity,which ranges from 0 S/m to90 S/*** increased number of nanosheets in stacks and a larger gap between them enhance the nanocomposite's ***,the thicker interphase and smaller tunneling size can lead to higher sample conductivity due to their optimistic effects on the percolation threshold and network efficacy.

关键词： graphene polymer composite stacked nanosheet tunneling conductivity contact resistance interphase

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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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cancer biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Taol Yuekui Wang Minghui Zeng' Yuqin Lil Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical UniversityTianjin 300192China Department of Hepatology Tianjin Second People's HospitalTianjin 300192China Tianjin Institute of Hepatology Tianjin 300192China Department of Hepatobiliary Oncology Liver Cancer CenterTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Centerfor CancerTianjin300060China

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University cancer Institute&Hospital)between April 2021 and December 2023 were *** were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56%vs.8.89%;Pgroup were significantly higher than the CHB *** MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all ***:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B hepatocellular carcinoma immunotherapy efficacy

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Advances in regional nodal management of early-stage breast cancer

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Chinese Journal of cancer Research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

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Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for Liver cancer The Naval Medical UniversityShanghai 201805China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China Laboratory of Signaling Regulation and Targeting Therapy of Liver cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system cancer Homeostasis Liver diseases SOX9

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Sexual dimorphism in the antitumor immune responses elicited by the combination of fasting and chemotherapy

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cancer Communications 2024年第4期44卷 508-513页

作者： Andrés Pastor-Fernández Manuel Montero Gómez de las Heras Jose Ignacio Escrig-Larena Marta Barradas Cristina Pantoja Adrian Plaza Jose Luis Lopez-Aceituno Esther Durán Alejo Efeyan Maria Mittelbrunn Lola Martinez Pablo Jose Fernandez-Marcos Metabolic Syndrome group(BIOPROMET) Madrid Institute for Advanced Studies(IMDEA)FoodE28049MadridSpain Molecular biology Center Severo Ochoa(CBMSO) Spanish National Research Council(CSIC)Madrid Autonoma University(UAM)MadridSpain Department of Basic Medical Sciences Institute of Applied Molecular MedicineSchool of MedicineUniversity Studies Center(CEU)-San Pablo UniversityMadridSpain Metabolism and Cell Signaling Laboratory Spanish National cancer Research Centre(CNIO) MadridSpain 5Flow Cytometry UnitBiotechnology ProgrammeSpanish National Cancer Research Centre(CNIO)MadridSpain

Fasting reduces chemotherapy toxicity[1],enhances immunogenic tumor cell death[2,3]and increases CD8^(+)T cell infiltration in tumors,particularly when combined with chemotherapy[2,3]or immunotherapy[4].More-over,fast... 详细信息

关键词： chemotherapy fasting immune

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Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1291-1300页

作者： Chong-Yuan Sun Xiao-Jie Zhang Zheng Li He Fei Ze-Feng Li Dong-Bing Zhao Department of Pancreatic and Gastric Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The prognostic nutritional index(PNI),a marker of immune-nutrition balance,has predictive value for the survival and prognosis of patients with various *** To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma(AC)patients who underwent curative *** The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December *** patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve *** compared disease-free survival(DFS)and overall survival(OS)between these groups and assessed prognostic factors through univariate and multivariate *** The optimal cutoff value for the PNI was established at *** with a PNI≥45.3 were categorized into the PNI-high group,while those with a PNIgroup tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high *** 5-year OS rates for patients with a PNI≥45.3 and a PNIgroup had shorter OS(P=0.006)and DFS(P=0.012).In addition,multivariate analysis revealed that the PNI,pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and *** The PNI is a straightforward and valuable marker for predicting long-term survival after *** PNI should be incorporated into the standard assessment of patients with AC.

关键词： Ampullary carcinoma Prognostic nutritional index Prognosis Pancreaticoduodenectomy

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2024年

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Luoshan Center for Disease Control and Prevention Office for cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer(GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates(CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic(atrophic gastritis/intestinal metaplasia) and neoplastic lesions(low-grade/high-grade dysplasia), respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients(≥3 risk factors) with non-neoplastic lesions showed higher GC risks(adjusted HR=7.73, 95%CI: 4.29–13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions(aHR=3.07, 95%CI: 1.67–5.64) and high-risk patients with mild lesions(aHR=7.29, 95%CI: 3.58–14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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