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Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

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Protein & Cell 2021年第2期12卷 128-144页

作者： Chengcheng Wang Taiping Zhang Quan Liao menghua dai Junchao Guo Xinyu Yang Wen Tan Dongxin Lin Chen Wu Yupei Zhao Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Etiology and Carcinogenesis National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China CAMS Oxford Institute(COI) Chinese Academy of Medical SciencesBeijing 100730China

Pancreatic ductal adenocarcinoma(PDAC)has poor prognosis due to limited therapeutic *** study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic *** have identified HNF4G gene whose silencing most effectively repressed PDAC cell ***4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor *** HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC(log-rank P=0.036;HR=1.60,95%CI=1.03–2.47).We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 ***,Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC(log-rank P=0.022;HR=0.31,95%CI=0.14–0.68)but not in patients with SMAD4-normal *** analysis shows that HNF4G may act in PDAC through the cell-cell junction *** results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

关键词： pancreatic cancer HNF4G SMAD4 deficiency SMAD4-deficient PDAC Metformin

Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5444-5453页

作者： Ming Cui Ya Hu Zejian Zhang Tianqi Chen menghua dai Qiang Xu Junchao Guo Taiping Zhang Quan Liao Jun Yu Yupei Zhao Department of General Surgery Key Laboratory of Research in Pancreatic TumorState Key Laboratory of Complex Severe and Rare DiseaseNational Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College HospitalPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100730China Department of Medical Research Center State Key Laboratory of Complex Severe and Rare DiseaseNational Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College HospitalPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100730China Department of Medicine Oncologyand SurgeryJohns Hopkins University School of MedicineBaltimoreMD21224USA Pancreas center Tianjin Medical University Cancer Institute and HospitalTianjin300060China

Pancreatic cystic neoplasms(PCNs)are recognized as precursor lesions of pancreatic cancer,with a marked increase in *** detection of malignant PCNs is crucial for improving prognosis;however,current diagnostic methods are insufficient for accurately identifying malignant ***,we utilized mass spectrometry(MS)-based glycosite-and glycoform-specific glycoproteomics,combined with proteomics,to explore potential cyst fluid diagnostic biomarkers for *** glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated,and its characteristics during the malignant transformation of PCN were *** the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN,a group of cyst fluid glycoprotein biomarkers was *** parallel reaction monitoring(PRM)-based targeted glycoproteomic analysis,we validated these chosen glycoprotein biomarkers in a second cohort,ultimately confirming N-glycosylated PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0),CEACAM5(Asn-197,H5N4F0S0)and ATP6V0A4(Asn-367,H6N4F0S0)as promising diagnostic biomarkers for distinguishing malignant *** glycoprotein biomarkers exhibited robust performance,with an area under the curve ranging from 0.771 to *** conclusion,we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for *** findings hold significant clinical implications,providing valuable insights for PCN decision-making,and potentially offering therapeutic targets for PCN treatment.

关键词： neoplasms offering utilized

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy

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Hepatobiliary Surgery and Nutrition 2023年第6期12卷 868-881页

作者： Zhihong Chen Ning Shi Cheng Xing Yiping Zou Yuanpeng Zhang Zhenrong Chen Fan Wu Haosheng Jin Rufu Chen menghua dai Department of General Surgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Department of General Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhouChina Medical College of Shantou University ShantouChina National Translational Medicine of China BeijingChina Department of General Surgery Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina

Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains *** studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with ***:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent *** hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion *** constituted the training cohort and the validation cohort,*** and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk *** nomogram was constructed and *** index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical ***,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the ***:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH *** postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,***,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk *** nomogram demonstrated significant predictive utility for post-pancreatectomy *** C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,*** curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction resu

关键词： New-onset diabetes mellitus(NODM) pancreatic benign or low-grade malignant lesions(PBLML) distal pancreatectomy(DP) nomogram

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胰腺术后急性胰腺炎的研究进展

中华外科杂志 2023年第7期61卷 609-613页

作者：陈昊民戴梦华中国医学科学院、北京协和医学院、北京协和医院基本外科北京100730

胰腺术后急性胰腺炎(PPAP)是多种因素引起的术后早期残胰急性炎症,随着研究的深入,已证实其是术后胰瘘等严重并发症的独立危险因素。少数PPAP进展为坏死性PPAP后会增加患者的死亡风险。国际胰腺外科研究组综合考虑了血清淀粉酶、影像学... 详细信息

胰腺术后急性胰腺炎(PPAP)是多种因素引起的术后早期残胰急性炎症,随着研究的深入,已证实其是术后胰瘘等严重并发症的独立危险因素。少数PPAP进展为坏死性PPAP后会增加患者的死亡风险。国际胰腺外科研究组综合考虑了血清淀粉酶、影像学检查结果、临床影响等因素,将PPAP作为一种独立并发症进行标准化定义和分级。本综述主要回顾了PPAP概念提出历程,总结了其病因、预后、防治相关研究的最新进展。但鉴于相关研究存在较大异质性,且多为回顾性研究,未来有必要提高对PPAP的重视程度,通过更多标准化的研究阐明问题,从而优化胰腺术后并发症的预防与处理。

关键词：胰腺炎手术后并发症术后胰瘘高淀粉酶血症胰十二指肠切除术

Value of contrast-enhanced ultrasound combined with percutaneous ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic lesions

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Chinese Medical Journal 2022年第4期135卷 426-432页

作者： Yang Gui menghua dai Zhilan Meng Xiaoyan Chang Li Tan Jing Zhang Xueqi Chen Tongtong Zhou Qing Zhang Mengsu Xiao Ke Lyu Yuxin Jiang Department of Ultrasound State Key Laboratory of Complex Severe and Rare DiseasesPecking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeDongcheng DistrictBeijing 100730China Department of Surgery State Key Laboratory of Complex Severe and Rare DiseasesPecking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeDongcheng DistrictBeijing 100730China Department of Pathology State Key Laboratory of Complex Severe and Rare DiseasesPecking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeDongcheng DistrictBeijing 100730China

Background:Contrast-enhanced ultrasound(CEUS)can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the *** retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound(US)-guided fine-needle aspiration(FNA)with or without CEUS ***:Clinical,imaging,and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital,with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively *** were divided into CEUS and US groups according to whether CEUS was performed before the *** to FNA cytology diagnoses,we combined non-diagnostic,neoplastic,and negative cases into a negative *** positive category included malignant,suspicious,and atypical *** final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 *** sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of US-FNA were evaluated between the two ***:This study enrolled 107 male and 74 female patients(average age:60 years).There were 58 cases in the US group and 123 cases in the CEUS *** statistically significant differences in age,gender,or lesion size were found between the two *** diagnostic accuracy of the CEUS group was 95.1%(117/123),which was higher than the 86.2%(50/58)observed in the US group(P=0.036).The sensitivity,specificity,PPV,and NPV of the CEUS group were increased by 7.5%,16.7%,3.4%,and 18.8%,respectively,compared with the US ***,the differences of the two groups were not statistically ***:Compared with the conventional US,the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy,especially for some complicated FNA cases.

关键词： Biopsy Contrast-enhanced ultrasound Cytology Fine-needle aspiration Pancreatic lesion Pancreatic neoplasms Percutaneous ultrasound

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胰腺癌新辅助治疗和转化治疗的研究进展

中华外科杂志 2017年第1期55卷 69-72页

作者：胡丹旦戴梦华中国医学科学院北京协和医学院北京协和医院基本外科 100730

胰腺癌是转移倾向明显的高度恶性肿瘤，手术治疗有效但复发率高。通过新辅助治疗，部分患者可实现降期、增加切缘阴性率、降低淋巴结阳性率、减少血管侵犯等，但存在增加手术难度、延误手术时机、疗效评估指标不成熟等争议。具有高危因... 详细信息

胰腺癌是转移倾向明显的高度恶性肿瘤，手术治疗有效但复发率高。通过新辅助治疗，部分患者可实现降期、增加切缘阴性率、降低淋巴结阳性率、减少血管侵犯等，但存在增加手术难度、延误手术时机、疗效评估指标不成熟等争议。具有高危因素的可切除胰腺癌患者可积极行新辅助治疗，交界可能切除的病例建议新辅助治疗，同时转化治疗可能改善晚期胰腺癌患者预后。晚期胰腺癌一线化疗方案FOLFIRINOX可用于新辅助治疗。

关键词：胰腺肿瘤药物疗法联合新辅助治疗转化治疗

Early drain removal after major pancreatectomy reduces postoperative complications:a single-center,randomized,controlled trial

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Journal of Pancreatology 2020年第2期3卷 93-100页

作者： dai menghua Liu Qiaofei Xing Cheng Kleeff Jorg Liao Quan Guo Junchao Han Xianlin Xu Qiang Wang Shunda Department of General Surgery Peking Union Medical College Hospital(PUMCH)Peking Union Medical College&Chinese Academy of Medical SciencesBeijingChina Department of Visceral Vascular and Endocrine SurgeryMartin-Luther-University Halle-WittenbergHalleGermany

Objectives:Timing of drain removal and its effects on complications after major pancreatectomy remain *** designed this study to assess whether early drain removal after major pancreatectomy influences the incidence of complications in the patients with low risk of postoperative pancreatic fistula(POPF).Methods:This is a single-center randomized controlled trial(RCT).A total of 144 patients undergoing pancreaticoduodenectomy(PD)and distal pancreatectomy(DP)who met the criteria,including drain amylase on postoperative day(POD)1 and 3 less than 5000 U/L and drain output within POD 3 less than 300 mL/d,were randomly assigned to early drain removal(POD 3)or standard drain removal(≥POD 5).The primary outcome was major complications(Clavien-Dindo grades 2-4),and the secondary outcome was POPF,reintervention treatment,readmission,and total medical expense within 3 months after ***:A total of 5 patients in early drain removal group had at least 1 major complications(grades 2-4),compared to 15 patients in standard drain removal group(P=.028).The incidence of grade B/C pancreatic fistula was not significantly different(2.8%vs 0%).Multivariate analysis demonstrated that early drain removal was an independent factor associated with a reduced risk of major complications(P=.039,odds ratio=0.314).Majority of major complications occurred in PD patients,and only very few cases occurred in DP *** analysis showed that early drain removal significantly reduced the major complications only in the patients undergoing ***:This single-center RCT shows early drain removal on POD 3 is safe for both DP and PD patients,under our *** drain removal could reduce the incidence of major complications in patients undergoing PD.

关键词： Complications Distal pancreatectomy Drain removal Pancreaticoduodenectomy

胰腺癌患者新辅助治疗前后营养状况的改变及其对术后结局和预后的影响

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中华外科杂志 2020年第10期58卷 754-757页

作者：余张萍陈伟戴梦华中国医学科学院北京协和医学院北京协和医院基本外科100730 中国医学科学院北京协和医学院北京协和医院临床营养科100730

新辅助治疗已成为临界可能切除和局部进展期胰腺癌的标准治疗之一,但其可能在控制肿瘤进展的同时加重胰腺癌患者的营养不良,从而影响这部分患者的术后结局及长期预后。通过回顾相关文献发现,新辅助治疗会在不同程度上造成患者术前营养... 详细信息

新辅助治疗已成为临界可能切除和局部进展期胰腺癌的标准治疗之一,但其可能在控制肿瘤进展的同时加重胰腺癌患者的营养不良,从而影响这部分患者的术后结局及长期预后。通过回顾相关文献发现,新辅助治疗会在不同程度上造成患者术前营养状况恶化,但及时有效的营养干预可改善这种情况。这也提示有必要对接受新辅助治疗的患者进行早期营养干预以改善预后。但鉴于目前相关研究有限,且均存在一定局限性,未来仍需更多严谨、系统的研究来阐明问题,为早期对行新辅助治疗的胰腺癌患者进行有效的营养干预提供依据。

关键词：新辅助治疗胰腺癌患者术后结局营养干预肿瘤进展营养状况长期预后改善预后

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腹腔镜下半旋转胰头动脉优先入路胰十二指肠切除术的临床意义

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中华普外科手术学杂志（电子版） 2018年第4期12卷 275-278页

作者：戴梦华北京协和医院基本外科 100730

近年来,随着腹腔镜技术的成熟、3D及高清腹腔镜视频技术的发展和医疗止血器械的革新,目前腹腔镜胰十二指肠切除术(LPD)已经广泛应用于临床,并证实了LPD技术的可行性和安全性。LPD在胰头癌的治疗中也得到了广泛的应用,开腹胰腺癌R0切除技... 详细信息

近年来,随着腹腔镜技术的成熟、3D及高清腹腔镜视频技术的发展和医疗止血器械的革新,目前腹腔镜胰十二指肠切除术(LPD)已经广泛应用于临床,并证实了LPD技术的可行性和安全性。LPD在胰头癌的治疗中也得到了广泛的应用,开腹胰腺癌R0切除技术,例如联合门静脉/肠系膜上静脉(PV/SMV)切除重建和动脉优先入路等在LPD中也得到了广泛开展,在LPD中的优势已获得了越来越多外科医生的认可。笔者在借鉴开腹小肠系膜旋转的OPD术式,在结合腹腔镜视野角度的优势,提出了胰头半周旋转动脉优先入路的LPD术式,其目的是为了增加胰头癌的R0切除率,降低钩突切除过程中的出血风险。本文将就该术式在LPD中的应用及其特点展开讨论,进一步论述该术式的临床意义。

关键词：胰腺肿瘤腹腔镜检查胰十二指肠切除术