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A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

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Science China(Life Sciences) 2022年第11期65卷 2205-2217页

作者： Chang Gong Ziliang Cheng Yaping Yang Jun Shen Yingying Zhu Li Ling Wanyi Lin Zhigang Yu Zhihua Li Weige Tan Chushan Zheng Wenbo Zheng Jiajie Zhong Xiang Zhang Yunjie Zeng Qiang Liu RStephanie Huang Andrzej LKomorowski Eddy SYang François Bertucci Francesco Ricci Armando Orlandi Gianluca Franceschini Kazuaki Takabe Suzanne Klimberg Naohiro Ishii Angela Toss Mona PTan Mathew A Cherian Erwei Song Guangdong Provincial key laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineBreast Tumor CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Radiology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Clinical Research Design Division Clinical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Medical Statistics School of Public HealthSun Yat-sen UniversityGuangzhou 510080China Department of Breast Surgery the Second Affiliated HospitalShandong UniversityJinan 250033China Department of Breast Surgery Key Laboratory of Breast DiseasesThird Hospital of NanchangNanchang 330009China Department of Breast Surgery the First Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China Department of Pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Experimental and Clinical Pharmacology University of MinnesotaMinneapolisMN 55455USA Department of Surgery College of MedicineUniversity of RzeszówRzeszów 35-959Poland Department of Radiation oncology O’Neal Comprehensive Cancer CenterUniversity of Alabama at Birmingham School of MedicineBirminghamALUSA Laboratoty of Predictive oncology Institut Paoli-CalmettesCentre de Recherche en Cancérologie de MarseilleINSERM UMR1068CNRS UMR725MarseilleFrance Department of Drug Development and Innovation(D3i) Institut CurieParis 75005France Comprehensive Cancer Center UOC di Oncologia MedicaFondazione Policlinico Universitario A.Gemelli IRCCSRome 00168Italy Multidisciplinary Breast Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Breast Surgery Department of Surgical OncologyRoswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Surgery MD Anderson Cancer CenterHoustonTX 77030USA Department of Plastic and Reconstructive Surgery

Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,*** who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer.

关键词： hormone receptor-positive breast cancer micro RNA signature neoadjuvant chemotherapy dynamic contrast-enhanced magnetic resonance imaging nomogram

Oral Contraceptives and Health Outcomes:an Umbrella Review of Systematic Reviews and Meta-analyses in Women and Offspring

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Journal of Nutritional oncology 2022年第1期7卷 9-37页

作者： Yuan Lin Zou Rui Peng Ke Di Xu Xiao Ru Jiang Qiu Yu Sun Chun Hua Song Department of Epidemiology and Statistics College of Public HealthZhengzhou UniversityZhengzhou 450001HenanChina Henan key laboratory of Tumor Epidemiology Zhengzhou UniversityZhengzhou 450052HenanChina state key laboratory of Esophageal Cancer Prevention&Treatment Zhengzhou UniversityZhengzhou450052HenanChina Department of Teaching and Research Third Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052HenanChina

Aim We herein provide an umbrella review of systematic reviews(SR)and meta-analyses(MAs)of studies of the association of oral contraceptives(OCs)with the risks of multiple health outcomes in women and their *** Two investigators retrieved publications from four electronic databases,including PubMed,Embase,Web of Science,and the Cochrane Database of Systematic Reviews up to March 15,*** each association,random/fixed-effects summary effect size and 95%CIs were *** and publication bias were also *** method quality and evidence level for each publication were respectively assessed utilizing the AMSTAR and GRADE *** A total of 68 articles with 82 unique outcomes were included based on the eligibility *** lines of evidence indicated that OCs had effects on nearly all cardiovascular disease-related outcomes,especially for cerebral venous sinus thrombosis(OR=7.59,95%CI:3.82-15.09).Harmful associations were also found for vulvar vestibulitis(OR=2.31,95%CI:1.03-5.16),preterm birth(OR=1.17,95%CI:1.07-1.27),miscarriage(OR=1.13,95%CI:1.02-1.72),ulcerative colitis(OR=1.22,95%CI:1.06-1.41),Crohn's disease(OR=1.24,95%CI:1.09-1.40),alveolar osteitis(RR=1.86,95%CI:1.66-2.08),dry socket(RR=1.8,95%CI:1.33-2.43),and interstitial cystitis(OR=2.1,95%CI:1.26-3.49).However,oral contraceptives did not increase the risk of cancer except breast and cervical *** exposure to OCs was linked to an increased risk for the development of respiratory atopic disorders such as asthma(OR=1.1,95%CI:1.02-1.19)and rhinitis(OR=1.34,95%CI:1.07-1.68).Conclusion In summary,although their use obviously reduces the risk of pregnancy-and parturition-related morbidity and mortality for women,OCs were frequently related to more harm than benefit in terms of other health *** was true for both women and their descendants in this umbrella *** large-scale prospective studies analysing different doses,structures,a

关键词： Contraception Health outcomes Umbrella review Meta-analysis Systematic review

CFTR is a negative regulator ofγδT cell IFN-γproduction and antitumor immunity

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Cellular & Molecular Immunology 2021年第8期18卷 1934-1944页

作者： Yuanyuan Duan Guangqiang Li Miaomiao Xu Xiaofei Qi Mingxia Deng Xuejia Lin Zhiwei Lei Yi Hu Zhenghu Jia Quanli Yang Guangchao Cao Zonghua Liu Qiong Wen Zhenhua Li Jie Tang Wei Kevin Zhang Pingbo Huang Limin Zheng Richard A.Flavell Jianlei Hao Zhinan Yin Zhuhai Precision Medical Center Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Jinan UniversityZhuhai519000GuangdongChina The Biomedical Translational Research Institute Faculty of Medical ScienceJinan UniversityGuangzhou510632GuangdongChina Department of Physiology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515GuangdongChina The First Affiliated Hospital Jinan UniversityGuangzhou510632China School of Pharmaceutical Sciences South-Central University for NationalitiesWuhan430074HubeiChina Division of Life Science Hong Kong University of Science and Technology(HKUST)Hong KongChina state key laboratory of oncology in Southern China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou510060China Department of Immunobiology School of MedicineYale UniversityNew HavenCT06520USA

CFTR,a chloride channel and ion channel regulator studied mostly in epithelial cells,has been reported to participate in immune regulation and likely affect the risk of cancer ***,little is known about the effects of CFTR on the differentiation and function ofγδT *** this study,we observed that CFTR was functionally expressed on the cell surface ofγδT *** deletion and pharmacological inhibition of CFTR both increased IFN-γrelease by peripheralγδT cells and potentiated the cytolytic activity of these cells against tumor cells both in vitro and in ***,the molecular mechanisms underlying the regulation ofγδT cell IFN-γproduction by CFTR were either TCR dependent or related to Ca^(2+)*** was recruited to TCR immunological synapses and attenuated Lck-P38 MAPK-c-Jun *** addition,CFTR was found to modulate TCR-induced Ca^(2+)influx and membrane potential(Vm)-induced Ca^(2+)influx and subsequently regulate the calcineurin-NFATc1 signaling pathway inγδT ***,CFTR serves as a negative regulator of IFN-γproduction inγδT cells and the function of these cells in antitumor *** investigation suggests that modification of the CFTR activity ofγδT cells may be a potential immunotherapeutic strategy for cancer.

关键词： CFTR γδT cells TCR Membrane potential Antitumor immunity

The efficacy of bevacizumab in Chinese patients with metastatic colorectal cancer and its effect in different line setting

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The Chinese-German Journal of Clinical oncology 2014年第4期13卷 169-173页

作者： Chenxi Yin Chang Jiang Fangxin Liao Yuming Rong Wenzhuo He Xiuyu Cai Guifang Guo Huijuan Qiu Xuxian Chen Bei Zhang Liangping Xia state key laboratory of oncology in South China Sun Yat-sen University Cancer Center VIP Region Sun Yat-sen University Cancer Center Collaborative Innovation Center for Cancer Medicine

Objective: We aimed to evaluate the effect of bevacizumab in the palliative treatment of Chinese metastatic colorectal cancer(mCRC) and its efficacy in different lines. Methods: Patients of mCRC treated with bevacizumab or not at Sun Yat-sen University Cancer Center from 2005 to 2013 were recruited as the study group and control group. The endpoints were objective response rate(ORR), disease control rate(DCR), overall survival(OS) and progression free survival(PFS). The OS and PFS of first-, second- and third-line treatment groups were compared between study group and control group. Results: The median PFS of the study and the control group were 8.2 months(7.0–9.4 months), 5.7 months(4.7–6.6 months), P = 0.001; OS were 26 months(5.4–130.5 months), 18 months(16.6–19.4 months), P < 0.001, respectively. The ORR and DCR of first-, second- and third-line were 30.3%(20/66), 20%(6/30), 17.6%(3/17) and 97%(64/66), 86.7%(26/30), 100%(17/17). In the first-line chemotherapy group, the OS of the study group and the control group were 22.9(5.4–96.7) months and 18(16.6–19.4) months(P < 0.001); PFS were 9.4(8.4–10.4) months and 5.7(4.7–6.6) months(P < 0.001), respectively. While in the second- and third-line setting, only OS were statistically different, PFS had no significant difference. Conclusion: The combination of bevacizumab and chemotherapy had a promising short-term and long-term efficacy in Chinese mCRC patients than those without bevacizumab regimens, and the effect could be better reflected in the first-line treatment.

关键词： bevacizumab chemotherapy metastatic colorectal cancer efficacy

Genome of the Giant Panda Roundworm Illuminates Its Host Shift and Parasitic Adaptation

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Genomics, Proteomics & Bioinformatics 2022年第2期20卷 366-381页

作者： Yue Xie Sen Wang Shuangyang Wu Shenghan Gao Qingshu Meng Chengdong Wang Jingchao Lan Li Luo Xuan Zhou Jing Xu Xiaobin Gu Ran He Zijiang Yang Xuerong Peng Songnian Hu Guangyou Yang Department of Parasitology College of Veterinary MedicineSichuan Agricultural UniversityChengdu 611130China Agricultural Genomics Institute Chinese Academy of Agricultural SciencesShenzhen 518120China state key laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Department of oncology and Pathology Karolinska InstitutetStockholm 17164Sweden Department of Urology Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA Chengdu Research Base of Giant Panda Breeding Chengdu 610081China Institute of Animal Genetics and Breeding College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China Department of Civil and Environmental Engineering University of MarylandCollege ParkMD 20740USA Department of Chemistry College of Life and Basic ScienceSichuan Agricultural UniversityChengdu 611130China University of Chinese Academy of Sciences Beijing 100049China

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboofeeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda ***,we present a 293-megabase chromosome-level genome assembly of *** to infer its biology,including host *** genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new *** and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that *** undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut ***,we characterized the secretome of *** and predicted potential drug and vaccine targets for new control ***,this genome resource provides new insights into the host adaptation of *** to the giant panda as well as the host-shift events in ascaridoid parasite *** findings on the unique biology of *** will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

关键词： Giant panda Baylisascaris genome Host shift Parasitism evolution Host adaptation

XCL1/Glypican-3 fusion protein induces potent CD8^+ T-cell generation and enhances the anti-PD1 effect to suspend hepatocellular carcinoma development

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Cancer Biology & Medicine 2018年第S1期15卷 17-18页

作者： Kun Chen Yanmei Wang Hong Zhao Zhiyuan Wu Xinyu Bi Jianguo Zhou Dongmei Wang Jianqiang Cai Chunfeng Qu Department of Immunology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina state key laboratory of Molecular oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective:To induce potent CD8^+T-cells against glypican-3(GPC3),which is overexpressed in hepatocellular carcinoma(HCC),to suspend tumor ***:Since the chemokine receptor XCR1 is selectively expressed on professional ... 详细信息

关键词： XCL1/Glypican-3 fusion protein

Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells

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Journal of Pharmaceutical Analysis 2021年第6期11卷 799-807页

作者： Ebony Nottingham Elizabeth Mazzio Sunil Kumar Surapaneni Shallu Kutlehria Arindam Mondal Ramesh Badisa Stephen Safe Arun K.Rishi Mandip Singh Department of Pharmaceutics College of Pharmacy and Pharmaceutical SciencesFlorida A&M UniversityTallahasseeFL32307USA Department of Veterinary Physiology and Pharmacology College of Veterinary MedicineTexas A&M UniversityCollege StationTX77843USA John D.Dingell VA medical Center and Department of oncology Wayne State UniversityDetroitMI48201USA

Non-small cell lung cancer(NSCLC)is often characterized by an underlying mutation in the epidermal growth factor receptor(EGFR),contributing to aggressive metastatic *** 2-cyano-3,11-dioxo-18 beta-olean-1,12-dien-30-oate(CDODA-Me),a glycyrrhetinic acid derivative,reportedly improves the therapeutic response to erlotinib(ERL),an EGFR tyrosine kinase *** the present study,we performed a series of studies to demonstrate the efficacy of CDODA-Me(2μM)in sensitizing HCC827 R(ERL-resistant)cells to ***,we first established the selectivity of ERL-induced drug resistance in the HCC827 R cells,which was sensitized when ERL was combined with CDODA-Me(2μM),shifting the IC50 from 23.48μM to 5.46μ***,whole transcriptomic microarray expression data demonstrated that the combination of ERL+CDODA-Me elicited 210 downregulated genes(0.44%of the whole transcriptome(WT))and 174 upregulated genes(0.36%of the WT),of which approximately 80%were unique to the ERL+CDODA-Me *** effects centered on losses to cell cycle progression transcripts,a reduction of minichromosome maintenance complex components(MCM2-7),all key components of the Cdc45·MCM2-7 GINS(CMG)complex,and replicative helicases;these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress,including sulfiredoxin 1,heme oxygenase 1,and stress-induced growth inhibitor ***,these findings indicate that the synergistic therapeutic effects of ERL+CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.

关键词： Transcriptomic analysis Combination therapy Drug resistance Erlotinib Epidermal growth factor receptor

Progress and remaining challenges in comprehensive gastric cancer treatment

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Holistic Integrative oncology 2022年第1期1卷 52-61页

作者： Zhi-Feng Miao Hanyu Chen Zhen-Ning Wang Jia-Fu Ji Han Liang Hui-Mian Xu Jiping Wang Department of Surgical oncology and General Surgery The First Hospital of China Medical UniversityShenyangChina key laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors Ministry of EducationChina Medical UniversityShenyangChina key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital&InstituteBeijingChina Department of Gastrointestinal Cancer Center Ward IPeking University Cancer Hospital&InstituteBeijingChina Department of Gastroenterology Key Laboratory of Cancer Prevention and TherapyNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjinChina Brigham and Women’s Hospital BostonUSA.

Gastric cancer(GC)is the fifth most common cancer among all cancer fields and currently the third most common cause of cancer-related deaths both in men and women ***,the incidence and mortality of GC significantly varies due to different eating habits and environmental and genetic factors in different ***,with the development of techniques and surgical equipment along with newly emerging drugs and therapeutics,the 5-year survival for GC patients has increased and the death rate has *** this perspective,based on current therapies in GC field around the world,we present a systematic discussion about the state of advanced clinical treatments including surgical resection,systemic chemotherapy,targeted therapy,radiotherapy and enhanced recovery after *** challenges remain which require further study and investigation,in this review,we mainly focus on the promising clinical treatment strategies in GC to date.

关键词： Gastric Cancer Comprehensive treatment Surgical resection Systemic therapy ERAS

Total mesorectal excision with or without preoperative chemoradiotherapy for resectable mid/low rectal cancer: a long-term analysis of a prospective, single-center, randomized trial

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Cancer Communications 2018年第1期38卷 773-782页

作者： Fulong Wang Wenhua Fan Jianhong Peng Zhenhai Lu Zhizhong Pan Liren Li Yuanhong Gao Hui Li Gong Chen Xiaojun Wu Peirong Ding Zhifan Zeng Desen Wan Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China Department of Colorectal Surgery Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Department of Radiation oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Gynecological oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510060GuangdongP.R.China

Background:The preliminary results of our phase II randomized trial reported comparable functional sphincter pres-ervation rates and short-term survival outcomes between patients undergoing total mesorectal excision(TME)with or without preoperative concurrent chemoradiotherapy(CCRT).We now report the long-term results after a median follow-up of 71 ***:Between March 23,2008 and August 2,2012,192 patients with T3-T4 or node-positive,resectable,mid/low rectal adenocarcinoma were randomly assigned to receive TME with or without preoperative *** following endpoints were assessed:cumulative rates of local recurrence and distant metastasis,disease-free survival(DFS),and overall survival(OS).Results:The data of 184 eligible patients were analyzed:94 patients in the TME group and 90 patients in the CCRT+TME *** the whole cohort,the 5-year DFS and OS rates were 84.8%and 85.1%,*** 5-year DFS rates were 85.2%in the CCRT+TME group and 84.3%in the TME group(P=0.969),and the 5-year OS rates were 83.5%in the CCRT+TME group and 86.5%in the TME group(P=0.719).The 5-year cumulative rates of local recur-rence were 6.3%and 5.0%(P=0.681),and the 5-year cumulative rates of distant metastasis were 15.0%and 15.7%(P=0.881)in the CCRT+TME and TME groups,*** significant improvements in 5-year DFS and OS were observed with CCRT by subgroup ***:Both treatment strategies yielded similar long-term outcomes.A selective policy towards preoperative CCRT is thus recommended for rectal cancer patients if high-quality TME surgery and enhanced chemotherapy can be performed.

关键词： Rectal cancer Total mesorectal excision Chemoradiotherapy Long-term outcomes Phase II randomized trial