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Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

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Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng department of Hepatobiliary-Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive cancer Center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic ***-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and ***-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been ***,the precise functions of these subtypes need to be studied and *** of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic *** clinical trials,including phase III trials targeting CAFs,have been performed ***,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be *** review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving ***,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of molecular medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Center for molecular Imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

Progression from ductal carcinoma in situ to invasive breast cancer:molecular features and clinical significance

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1841-1868页

作者： Jing Wang Baizhou Li Meng Luo Jia Huang Kun Zhang Shu Zheng Suzhan Zhang Jiaojiao Zhou The Key Laboratory of cancer Prevention and Intervention China National Ministry of Educationthe Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina department of Breast Surgery and Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial clinical Research Center for cancer HangzhouChina department of Pathology the Fourth Affiliated HospitalZhejiang University School of MedicineYiwuChina department of Plastic Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina cancer Center Zhejiang UniversityHangzhouChina

Ductal carcinoma in situ(DCIS)represents pre-invasive breast *** untreated cases,25-60%DCIS progress to invasive ductal carcinoma(IDC).The challenge lies in distinguishing between non-progressive and progressive DCIS,often resulting in over-or under-treatment in many *** increasing screen-detected DCIS in these years,the nature of DCIS has aroused worldwide attention.A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical ***,we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and *** also explored the molecular features of DCIS and IDC,shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor *** addition,valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing,spatial transcriptomics and artificial intelligence,have been systematically ***,we thoroughly discussed the clinical advancements in DCIS and IDC,including prognostic biomarkers and clinical managements,with the aim of facilitating more personalized treatment strategies in the *** on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

关键词： clinical breast alterations

Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children:analysis of 571 patients

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World Journal of Pediatrics 2024年第3期20卷 250-258页

作者： Min He Jia-Bin Cai Xuan Wu Yin-Bing Tang Jin-Yan Wang Jun-Qin Mao Ji-Jun Chen Li-Feng Zhang Zhong-Hai Guan Jie-Ni Xiong Wan-Xin Peng Jin-Hu Wang Ting Tao Pediatric cancer Research Center National Clinical Research Center for Child HealthHangzhouChina department of Surgical Oncology Children's HospitalZhejiang University School of MedicineHangzhouChina cancer Center Zhejiang UniversityNo.3333 Binsheng RodeHangzhouChina

Background Surgery plays an important role in the treatment of *** complications may impact the course of neuroblastoma *** date,comprehensive analyses of complications and risk factors have been *** Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and *** data collected included clinical characteristics,operative details,operative complications and postopera-tive *** factors for perioperative complications of retroperitoneal neuroblastoma were *** A total of 571 patients were enrolled in this *** complications were observed in 255(44.7%)*** leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent *** were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative *** Despite the high incidence of perioperative complications,the associated mortality rate was quite ***-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular *** with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.

关键词： Complication Neuroblastoma Risk factors Surgery

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 *** is best known to sense high cellular ADP or AMP levels,which indicate the depletion of energy *** studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic *** this study,we report that AMPK is also highly sensitive to extracellular matrix(ECM)*** 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 *** regulation of AMPK requires the Hippo kinases but not LKB1/*** kinases directly phosphorylate AMPKa at Thr172 to activate AMPK at low ECM ***,we found AMPK activity is inhibited in patients with pancreatic ductal adenocarcinoma(PDAC)with high ECM stiffness and is associated with a poor survival *** activation of Hippo kinases by ROCK inhibitor Y-27632 in combination with the mitochondrial inhibitor metformin synergistically activates AMPK and dramatically inhibits PDAC ***,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

Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents:a systematic review and meta-analysis

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World Journal of Pediatrics 2024年第6期20卷 569-580页

作者： Eun Joo Lee Miyoung Choi Sang Bong Ahn Jeong-Ju Yoo Seong Hee Kang Yuri Cho Do Seon Song Hong Koh Dae Won Jeon Hye Won Lee department of Pediatrics Yonsei University College of MedicineSeoulKorea clinical Evidence Research National Evidence-Based Healthcare Collaborating Agency(NECA)SeoulKorea department of Internal medicine Nowon Eulji Medical CenterEulji University College of MedicineSeoulKorea department of Internal medicine Soonchunhyang University Bucheon HospitalBucheonKorea department of Internal medicine Sangkye Paek HospitalInje University College of MedicineSeoulKorea Center for Liver and Pancreatobiliary cancer National Cancer CenterGoyangKorea department of Internal medicine College of MedicineSt.Vincent's HospitalThe Catholic University of KoreaSuwonKorea department of Internal medicine Hanyang University College of MedicineSeoulKorea department of Internal medicine Yonsei University College of MedicineSeoulKorea

Background As childhood obesity escalates worldwide,the prevalence of nonalcoholic fatty liver disease(NAFLD)in pediatric and adolescent populations is also ***,systematic studies and meta-analyses evaluating the prevalence of pediatric NAFLD remain *** The MEDLINE,Korean Medical Database(KMBASE),Embase,Global Health,and Cochrane Library databases were searched from January 1997 to April *** terms included NAFLD or steatosis;nonalcoholic or steatohepatitis;child(ren),adolescent,or teenager;and prevalence,incidence,or epidemiology.A random-effects meta-analysis model was used to estimate the prevalence of pediatric *** A total of 2116 publications were found,of which 62 were included in the *** them,27 reported the prevalence in the general population and 39 in the obese *** worldwide pooled prevalence of pediatric NAFLD was 13%[95%confidence interval(CI)9-18%]in the general population and 47%(95%CI 41%–53%)in the obese *** 16 studies in the general population and 18 in the obese population,NAFLD prevalence varied by *** the general population,the prevalence of NAFLD was 15%(95%CI 8%–23%)in males and 10%(95%CI 6%–15%)in *** the obese population,it was 54%(95%CI 46%–61%)in males and 39%(95%CI 30%–49%)in *** The global prevalence of pediatric NAFLD is rising in both the general and obese *** the increasing rates of childhood obesity,epidemiological studies on the prevalence and incidence of NAFLD are needed.

关键词： Meta-analysis Nonalcoholic fatty liver disease Pediatric Prevalence

cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017:a population-based registry study

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Science China(Life Sciences) 2024年第4期67卷 711-719页

作者： Yi Teng Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Siyi He Mengdi Cao Shaoli Zhang Qianru Li Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple *** aimed to report cancer profiles and trends among young adults in *** from the China cancer Registry Annual Report were used to estimate incidence and mortality among young adults(ages 20–49 years)in China in 2017,and an age-period-cohort model was employed to estimate the average annual percent change(AAPC)in incidence and mortality from 2000 to *** 25 cancer types were grouped into obesity-or overweight-associated cancers(12 cancer types)and additional cancers(13 cancer types).In 2017,there were 681,178new cases and 214,591 cancer deaths among young adults in *** young adults,the most common cancers were thyroid,breast,cervical,liver,lung,and colorectal cancer,and the leading causes of cancer deaths were liver,lung,cervical,stomach,breast,and colorectal *** 2000 to 2017,the cancer incidence increased for all cancers combined among young adults,with the highest AAPC(1.46%)for adults aged 20–24 years,while cancer mortality decreased,with the highest AAPC(-1.63%)for those aged 35–39 *** conclusion,the cancer incidence in China has increased among young adults,while cancer mortality has decreased for nearly all *** control measures,such as obesity control and appropriate screening,may contribute to reducing the increasing cancer burden among young adults.

关键词： young adults incidence mortality trends China

cancer profiles in China and comparisons with the USA:a comprehensive analysis in the incidence,mortality,survival,staging,and attribution to risk factors

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Science China(Life Sciences) 2024年第1期67卷 122-131页

作者： Siyi He Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer *** extracted data in five aspects of cancer incidence,mortality,survival,staging distributions,and attribution to risk factors in China,the USA and worldwide from open-source *** conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects,and compared cancer statistics between China and the USA.A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020,accounting for 25.1%and 30.2%of global cases,***-related cancers including lung cancer,colorectal cancer,and breast cancer showed an upward trend and have been the leading cancer types in China.41.6%of new cancer cases and 49.3%of cancer deaths occurred in digestive-system cancers in China,and the cancers of esophagus,nasopharynx,liver,and stomach in China accounted for over 40%of global ***-related cancers showed the highest population-attributable fractions among Chinese adults,and most cancers could be attributed to behavioral and metabolic *** proportions of stage I for most cancer types were much higher in the USA than in China,except for esophageal cancer(78.2%vs.41.1%).The 5-year relative survival rates in China have improved substantially during 2000–2014,whereas survival for most cancer types in the USA was significantly higher than in China,except for upper gastrointestinal *** findings suggest that although substantial progress has been made in cancer control,especially in digestive system cancers in China,there was still a considerable disparity in cancer burden between China and the *** robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.

关键词： cancer burden survival rate neoplasm staging risk factors China

molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal department of Medical and molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair