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MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by PI3K/AKT signaling pathway

oncology Research 2024年第3期32卷 517-528页

作者： YUANYUAN XU XIAOKE CHEN department of oncology surgery Shanghai Lung Cancer CenterShanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina

Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/***/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.

关键词： Lung adenocarcinoma Prognosis PI3K/AKT pathway Mitochondrial asparty-tRNA synthetase MicroRNAs

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Novel prognostic factors after radical resection of hepatocellular carcinoma: Updating an old issue

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World Journal of Gastrointestinal surgery 2024年第1期16卷 1-5页

作者： Lapo Bencini department of oncology and Robotic surgery Careggi Main Florence University and Regional HospitalFlorence 50134Italy

In this editorial,I comment on the article by Li et al published in the recent issue of the World Journal of Gastrointestinal surgery in 2023,investigating the role of some novel prognostic factors for early survival after radical resection of liver cancer.Liver cancer is an important burden among Asian and Western popu-lations,despite recent advances in both medicine(from virus eradication to systemic target therapies)and surgery.However,survival after proven radical surgery remains poor,with recurrences being the rule.Many prognostic scores have been developed and validated to select those patients who will best benefit from radical liver surgery,although the final general and oncological outcomes continue to be highly jeopardized.Unfortunately,no single biomarker can resolve all these issues for hepatocellular carcinoma,and it remains to be proven whether some of them main-tain predictive power in the long-term follow-up.In the ongoing era of“preci-sion”medicine,the novel prognostic markers,including immune inflammatory and nutritional indexes could be of great help in better stratify surgical candi-dates.

关键词： Hepatocellular carcinoma Liver cancer resection Liver surgery Prognostic factors Immune index Nutritional index

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Traumatic lumbar hernia: A systematic review of the literature

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Chinese Journal of Traumatology 2024年第1期27卷 53-57页

作者： Ioannis Tsouknidas Nikolaos Tasis Maria Ioanna Antonopoulou Vasileios Acheimastos Dimitrios KManatakis department of surgery Stony Brook University HospitalStony BrookNew YorkUSA department of Surgical oncology St Savvas Cancer HospitalAthensGreece nd department of surgery Athens Naval and Veterans HospitalAthensGreece department of surgery Naval Hospital of CreteChaniaGreece

Purpose:Traumatic lumbar hernia(TLH)constitutes a protrusion of content through a defect in the posterior abdominal wall,as a result of injury.This rare entity has been described in limited number of cases.Methods:A systematic review of the literature was performed according to the meta-analysis of observational studies in epidemiology guidelines.The English literature from 1990 until 2021 was reviewed,using PubMed,EMBASE and Google Scholar bibliographic databases,to identify case reports and case series with patients that were diagnosed with TLH.For each eligible study,demographics,clinical presentation,hernia characteristics,preoperative imaging investigations,operation details,and postoperative data were extracted for assessment.Statistical analysis was performed on SPSS,version 20.0.Results:A total of 62 studies were included for review,with 164 patients with TLH.Mean age was(42.6±14.3)years(47.6%males,31.1%females,gender not specified in 35 cases).Mean diameter of hernia neck was(6.3±3.1)cm,while the triangles of Petit and Grynfeltt were affected in 74.5%and 14.6%,respectively.Patients diagnosed in the emergency setting account for 54.2%,with CT scan establishing diagnosis in all but one case(97.7%).A delayed diagnosis was made in 45.8%,at a mean 1 year following trauma.Flank bulging(82.8%)and chronic back pain(34.3%)were the most frequent symptoms.In both delayed and acute group,open surgery(63.6%and 92.3%,respectively)was the preferred surgical approach.Postoperative complications were reported in 11.4%of acute and 15.0%of delayed patients.Hernia recurrence was 7%.Conclusions:TLH is uncommon with 164 cases described since 1990.CT scan is the gold standard in diagnosis.Open surgery is generally the preferred approach,particularly in the emergency setting.Acute TLH can be treated either by primary suture repair or mesh,depending on the local conditions,whereas delayed cases usually require a mesh.

关键词： Lumbar hernia Petit Grynfeltt Traumatic lumbar hernia Trauma

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Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer

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World Journal of Gastrointestinal oncology 2024年第3期16卷 933-944页

作者： Zhi-Wen Xu Jing-Tao Zhu Hao-Yu Bai Xue-Jun Yu Qing-Qi Hong Jun You department of Gastrointestinal oncology surgery The First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND Transanal endoscopic intersphincteric resection(ISR)surgery currently lacks sufficient clinical research and reporting.AIM To investigate the clinical effectiveness of transanal endoscopic ISR,in order to promote the clinical application and development of this technique.METHODS This study utilized a retrospective case series design.Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included.All patients underwent transanal endoscopic ISR as the surgical approach.We conducted this study to determine the perioperative recovery status,postoperative complications,and pathological specimen charac-teristics of this group of patients.RESULTS This study included 45 eligible patients,with no perioperative mortalities.The overall incidence of early complications was 22.22%,with a rate of 4.44%for Clavien-Dindo grade≥III events.Two patients(4.4%)developed anastomotic leakage after surgery,including one case of grade A and one case of grade B.Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients.The mean distance between the tumor lower margin and distal resection margin was found to be 2.30±0.62 cm.The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens.CONCLUSION Transanal endoscopic ISR is safe,feasible,and provides a clear anatomical view.It is associated with a low incidence of postoperative complications and favorable pathological outcomes,making it worth further research and application.

关键词： Intersphincteric resection Transanal Rectal cancer Complications Endoscopic

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Effects of dietary intervention on human diseases:molecular mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1389-1422页

作者： Yu-Ling Xiao Yue Gong Ying-Jia Qi Zhi-Ming Shao Yi-Zhou Jiang Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina department of oncology Shanghai Medical CollegeFudanUniversityShanghai200032China

Diet,serving as a vital source of nutrients,exerts a profound influence on human health and disease progression.Recently,dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases,autoimmune diseases,cardiovascular diseases,and metabolic disorders.These interventions have demonstrated substantial potential in modulating metabolism,disease trajectory,and therapeutic responses.Metabolic reprogramming is a hallmark of malignant progression,and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication.Dietary intake,as a key environmental factor,can influence tumor metabolism.Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors,thereby increasing the efficacy of cancer treatments.However,the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex.Despite encouraging results,the mechanisms underlying diet-based therapeutic strategies remain largely unexplored,often resulting in underutilization in disease management.In this review,we aim to illuminate the potential effects of various dietary interventions,including calorie restriction,fasting-mimicking diet,ketogenic diet,protein restriction diet,high-salt diet,high-fat diet,and high-fiber diet,on cancer and the aforementioned diseases.We explore the multifaceted impacts of these dietary interventions,encompassing their immunomodulatory effects,other biological impacts,and underlying molecular mechanisms.This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

关键词： diseases metabolism potential

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees department of surgery Vanderbilt University Medical CenterNashvilleTN 37232United States department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical oncology and Endocrine surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic findings.Metastatic disease is typically associated with increased tumor diameter,multifocality,and vascular invasion.We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid mass.Serial CT evaluations demonstrated steatosis,but no cirrhosis or liver lesions.Endoscopic ultrasound demonstrated a normal-appearing pancreas,biliary tree,and liver.Fine needle aspiration yielded atypical cells.The differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal tumor.After review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC.Magnetic resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 hyperintensity.Alpha fetoprotein was 23.3 ng/mL.The patient was diagnosed with HCC with portocaval nodal involvement.Review:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC.We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic HCC.CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary.In patients with risk factors fo

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer

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Genes & Diseases 2024年第3期11卷 338-350页

作者： Xin Xu Yuan Fang Somaira Nowsheen Ye-Xiong Li Zhenkun Lou Min Deng State Key Laboratory of Molecular oncology and department of Radiation oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of General surgery Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China department of General surgery Zhongshan HospitalFudan UniversityShanghai 200032China department of Dermatology University of California San DiegoSan DiegoCA 92093USA department of oncology Mayo ClinicRochesterMN 55905USA

The adenosine monophosphate(AMP)-activated protein kinase(AMPK)sits at a cen-tral node in the regulation of energy metabolism and tumor progression.AMPK is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy stores.Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.In this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)stiffness.We found that AMPK is activated in cells when cultured under low ECM stiffness conditions and is functionally required for the metabolic switch induced by ECM stiffness.This regulation of AMPK requires the Hippo kinases but not LKB1/CaMKKp.Hippo kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM stiffness.Furthermore,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival outcome.The activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC growth.Together,these findings establish a novel model for AMPK regulation by the mechanical properties of ECMs and provide a rationale for simultaneously targeting the ECM stiffness-Hippo kinases-AMPK signaling and low glucose-LKB1-AMPK signaling pathways as an effective therapeutic strategy against PDAC.

关键词： AMPKactivity Cellularmetabolic switch ECM stiffness Hippokinase signaling Pancreaticductal adenocarcinoma

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Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong MA Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG Jin-jie WU Ji-ping CHENG Yue-lei ZENG Lin ZHAO Ai-guang oncology department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China oncology department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal surgery department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China oncology department Fudan University Shanghai Cancer CenterShanghai200032China oncology department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China oncology department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China oncology department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China oncology department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China oncology department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China Shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC patients.Methods This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,2021.Overall survival(OS)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for bias.Results A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled.Among them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received CM.Two-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in first-line.The application of apatinib increased(33.33%)in third-line.The application of checkpoint inhibitors has increased since 2020.COX analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the OS of AGC.After PSM and IPTW,the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(P<0.001).Conclusions In real-world practice for AGC in China,therapy choices consisted with guidelines.Two-drug regimen was the main first-line choice.Standardized CM treatment was an independent prognostic factor and could prolong the OS of C

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

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Circular RNAs in breast cancer diagnosis,treatment and prognosis

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oncology Research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU SONG JINHUI ZHANG LEWEI ZHU HAILIN TANG department of Breast oncology surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China State Key Laboratory of oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China department of Breast surgery The First People’s Hospital of FoshanFoshan528000China

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

关键词： CircRNA Breast cancer Diagnosis Treatment Biomarker

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Quality assessment of surgery for colorectal cancer:Where do we stand?

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World Journal of Gastrointestinal surgery 2024年第4期16卷 982-987页

作者： Stefan Morarasu Cristian Livadaru Gabriel-Mihail Dimofte The Second department of Surgical oncology Regional Institute of OncologyIasi 707483Romania

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past decade.It has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units today.Total mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical societies.However,there are still ongoing discrepancies in outcomes largely based on surgeon performance.This is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume centers.Defining markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional level.With the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(i.***.arterial stumps)measured on postoperative scans as part of the routine cancer follow-up.There is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

关键词： Colorectal cancer Colon surgery Arterial stump Complete mesocolic excision Surgical quality

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