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Elevated DLL3 in stomach cancer by tumor-associated macrophages enhances cancer-cell proliferation and cytokine secretion of macrophages

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Gastroenterology Report 2022年第1期10卷 322-334页

作者： Jian-Bin Ye Jun-Jie Wen Dan-Lin Wu Bing-Xin Hu Mei-Qun Luo Yan-Qing Lin Yun-Shan Ning Yan Li School of Laboratory Medicine and Biotechnology Southern Medical UniversityGuangzhouGuangdongP.R.China Service Union Medicine Southern Medical UniversityZhuhaiGuangdongP.R.China

Background The notch signal pathway is important in the development of both tumor-associated macrophages(TAMs)and stomach cancer,but how Notch signaling affects TAMs in stomach cancer is barely understood.Methods The expressions of Notch1,Notch2,Notch3,Notch4,hes family bHLH transcription factor 1(Hes1),and delta-like canonical Notch ligand 3(DLL3)were detected by Western blot and the expressions of interleukin(IL)-10,IL-12,and IL1-b were detected using enzyme-linked immunosorbent assay after the co-culture of macrophages and stomach-cancer cells.The proliferation and migration of cancer cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay,respectively,and the cell cycle was detected using Annexin V/propidium iodide assay.The protein interactions with DLL3 were detected using co-immunoprecipitation and mass spectrometry.Results The co-culture of macrophages and stomach-cancer cells MKN45 and BGC823 could enhance cell proliferation accompanied by the activation of Notch1/Notch2 signaling and upregulation of DLL3.Notch signaling gamma-secretase inhibitor(DAPT)blocked this process.The overexpression of DLL3 in stomach-cancer cells could promote the proliferation of cancer cells,enhance the activation of Notch1/Notch2 signaling,induce the expression of IL-33,lead to the degradation of galectin-3–binding protein(LG3BP)and heat shock cognate 71 kDa protein(HSPA8),and result in elevated IL-1b,IL-12,and IL-10 secretion by macrophages.Higher expression of DLL3 or IL-33 could lead to a lower survival rate based on University of California,Santa Cruz Xena Functional Genomics Explorer and The cancer Genome Atlas data set.Conclusions This is evidence that DLL3 regulates macrophages in stomach cancer,suggesting that DLL3 may be a novel and potential target for stomach-cancer therapy.

关键词： stomach cancer DLL3 macrophages Notch signaling,proliferation cytokines

Incidence and mortality of stomach cancer in China,2014

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Chinese Journal of cancer Research 2018年第3期30卷 291-298页

作者： Lei Yang Rongshou Zheng Ning Wang Yannan Yuan Shuo Liu Huichao Li Siwei Zhang Hongmei Zeng Wanqing Chen Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Beijing Office for Cancer Prevention and ControlPeking University Cancer Hospital & Institute National cancer Center/cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College

Objective： In this study,we aimed to estimate the updated incidence and mortality rate of stomach cancer based on the cancer registration data in 2014,collected by the National Central cancer Registry of China（NCCRC）.Methods： In 2017,339 registries＇ data were qualified based on the criteria of data quality control of the NCCRC.Cases of stomach cancer were retrieved from the national database.We estimated numbers of stomach cancer cases and deaths in China using age-specific rates and corresponding national population stratified by area,sex,agegroup（0,1–4,5–9,10–14,…,85＋）.Chinese standard population in 2000 and Segi＇s world population were applied for age-standardized incidence and mortality rates.Results： In 2014,410,400 new stomach cancer cases and 293,800 cancer-associated deaths were estimated to have occurred in China.The crude incidence rate of stomach cancer was 30.00/100,000,age-standardized incidence rates by Chinese standard population（ASIRC） and by world standard population（ASIRW） were 19.62/100,000 and19.51/100,000,respectively.The crude mortality rate of stomach cancer was 21.48/100,000,age-standardized mortality rates by Chinese（ASMRC） and by world standard population（ASMRW） were 13.44/100,000 and13.30/100,000,respectively.Incidence and mortality rates in rural areas were both higher than that in urban areas.stomach cancer has a strong relationship with gender and age.The disease has occurred more frequently among men than women with a male to female ratio of 2.4 for ASIRC.After age group of 40-44 years,incidence rates are substantially higher in men than in women,same pattern was seen for age-specific mortality rates.Conclusions： There is still a heavy burden of stomach cancer in China.The incidence and mortality patterns of stomach cancer show substantial gender and regional disparities.Great effort is needed to provide more accessible health services,sufficient financial resources,and adequate cancer-care infrastructure for the Chinese population,especially for people living in rural areas.

关键词： Incidence mortality population-based stomach cancer

High scored thyroid storm after stomach cancer perforation: A case report

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World Journal of Clinical Cases 2022年第24期10卷 8768-8774页

作者： Seung Min Baik Yejune Pae Jae-Myeong Lee Department of Surgery Ewha Womans University Mokdong HospitalEwha Womans University College of MedicineSeoul 07985South Korea Department of Surgery College of MedicineGraduate School of Korea UniversitySeoul 02841South Korea Department of Acute Care Surgery Korea University Anam HospitalSeoul 02841South Korea

BACKGROUND Thyroid storm is a life-threatening emergency.Reportedly,the prevalence of thyroid storm is 1%-2%among patients admitted to the hospital for thyrotoxicosis.Burch and Wartofsky(1993)introduced a scoring system using precise clinical criteria to identify thyroid storms.Only 17 cases of thyroid storm with a score>70 points have been reported.Although thyroid storms are uncommon,their clinical findings resemble those of sepsis.CASE SUMMARY A 48-year-old man was referred to the emergency room from a local clinic owing to suspicion of gastric ulcer perforation;medications for hypertension,diabetes mellitus,and hyperthyroidism had been suspended 1 year prior to this visit.We performed an emergency distal gastrectomy with Billroth II anastomosis for gastric cardia cancer perforation,and the patient was referred to the surgical intensive care unit(ICU).On the 2nd d in the ICU,his body temperature(BT)increased to 41.3℃ at 19:00,with the thyroid storm score(90 points)peaking at 18:00(BT;41.2℃,pulse rate;138/min,irritable status).The patient was administered propylthiouracil,intravenous glucocorticoids,acetaminophen,and Lugol’s solution daily.Subsequently,we performed bladder irrigation with cold saline using a Foley catheter and applied a hypothermic blanket to decrease the patient's BT.His vital signs were stable on the 8th day in the ICU.CONCLUSION Thyroid storms are uncommon,with few reports in the literature;however,their clinical findings resemble those of sepsis and require further investigation.Since an untreated thyroid storm results in a high mortality rate,it should be investigated when managing sepsis.

关键词： Thyroid storm stomach cancer Severity score Sepsis Case report

Epidemiology of stomach cancer

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World Journal of Gastroenterology 2022年第12期28卷 1187-1203页

作者： Milena Ilic Irena Ilic Department of Epidemiology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia

Despite a decline in incidence and mortality during the last decades,stomach cancer is one of the main health challenges worldwide.According to the GLOBOCAN 2020 estimates,stomach cancer caused approximately 800000 deaths(accounting for 7.7%of all cancer deaths),and ranks as the fourth leading cause of cancer deaths in both genders combined.About 1.1 million new cases of stomach cancer were diagnosed in 2020(accounting for 5.6%of all cancer cases).About 75%of all new cases and all deaths from stomach cancer are reported in Asia.stomach cancer is one of the most lethal malignant tumors,with a five-year survival rate of around 20%.There are some well-established risk factors for stomach cancer:Helicobacter pylori infection,dietary factors,tobacco,obesity,and radiation.To date,the most important way of preventing stomach cancer is reduced exposure to risk factors,as well as screening and early detection.Further research on risk factors can help identify various opportunities for more effective prevention.Screening programs for stomach cancer have been implemented in a few countries,either as a national or opportunistic screening of high-risk individuals only.Generally,due to its high aggressiveness and heterogeneity,stomach cancer still remains a severe global health problem.

关键词： stomach cancer Epidemiology Incidence Mortality Survival Predictive factors Prevention

EPIDEMIC STRENGTH OF CARDIA AND DISTANT stomach cancer IN THE HIGH RISK REGION OF ESOPHAGEAL cancer AND THEIR IMPLICATION TO EDOSCOPIC SCREENING

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Chinese Journal of cancer Research 2006年第2期18卷 111-115页

作者：张立玮温登瑰李英赛于卫芳王顺平尔立绵丛庆文王俊和李素平李永伟马彩芬单宝恩王士杰 Department of Endoscopy The Fourth Hospital of Hebei Medical University Shijiazhuang 050011 Hebei cancer Institute Shijiazhuang 050011 Shexian County cancer Institute Shexian County 056400

Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to clarify the tasks for the control of upper gastrointestinal tract cancer as a whole in the region. Methods： Comparisons of incidence and mortality rates of esophageal, cardia and stomach cancers were made between Cixian, Linxian and Shexian Counties with reference to detection rates of cancer in situ and precancerous lesions of the three upper gastrointestinal cancers by endoscopic screening. The screening was performed from 1999 through 2004 in the three adjacent counties including a total of 6233 local residents aged 40 to 69 years old. Results： The incidence rates for cardia cancer for the male and female from 2000 through 2004 were 69.9 and 41.5, and the mortality rates were 54.3 and 33.2 respectively in Shexian County. Esophageal, cardia, and stomach cancers constitute about 70～80 percent of all malignant disease by incidence or mortality rates. Endoscopic survey with iodine staining can effectively detect squamous cell precancerous lesions in the esophagus, but the method is inadequate for the detection of adeno precancerous lesions of the cardia and stomach. Conclusion： The south Taihang mountain region is a high risk area not only for esophagus cancer, but also for cardia and stomach cancers. To control upper gastrointestinal tract cancers as a whole in the region, special attention should be paid to the control of cardia and stomach cancers. Presently, to find effective screening methods for detecting cardia and stomach precancerous lesions is especially important.

关键词： High-risk region for esophageal cancer Cardia cancer stomach cancer Precancerous disease Endoscopic screening

DLL3 in stomach cancer enhances cancer cell proliferation and regulates the immunity of tumor associated macrophages

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DLL3 in stomach cancer enhances cancer cell proliferation an...

The impact of stomach cancer mortality on life expectancy at birth:a decomposition analysis in east Asian countries from 1990 to 2019

第十三届全国免疫学学术大会

作者： Jianbin Ye Danlin Wu Junjie Wen Bingxin Hu Meiqun Luo Yan Li Yunshan Ning Southern Medical University

Background: stomach cancer is the fifth common cancer and the third leading cause of cancer death worldwide and the second incidence and mortality of cancer in China. Tumor-associated macrophages(TAMs), as part of the adaptive immune response, constitute a major portion of the leukocyte infiltrate in cancer. Studies have demonstrated the connection between stomach cancer and macrophages. Notch signal pathway is important in the development of both tumor associated macrophages(TAMs) and stomach cancer, but how Notch in stomach cancer affects TAMs is barely understood. Methods: THP-1 was induced into macrophages by PMA and co-cultured with stomach cancer cell line MKN45. Notch signaling proteins were detected by western blot,and IL-1β, IL-12 and IL-10 were detected by ELISA in the supernatant from co-culture. The transcriptome sequencing was performed to detect the genes regulated by DLL3 overexpression in MKN45.Results: We found that co-culture of macrophages and stomach cancer cell MKN45 could enhance MKN45 cell proliferation accompanied with activation of Notch1/Notch2 signaling and up-regulation of Notch ligand DLL3. Elevated DLL3 in MKN45 could promote cell proliferation, enhance activation of Notch1/Notch2 signaling, induce IL-33 expression, and lead to galectin-3-binding protein and heat shock cognate 71 kDa protein degradation in MKN45, which resulted in elevated IL-1β, IL-12 and IL-10 secretion by macrophages. Conclusions: This is the first report unveiling how Notch signal pathway especially DLL3 in stomach cancer regulates macrophages. And this will offer new possible targets for stomach cancer therapy.

关键词： Notch stomach cancer macrophages DLL3 IL-33

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China Population and Development Studies 2023年第4期7卷 325-341页

作者： Chunyong Chen Leiwen Jiang Siying Lyu Guillaume Marois Asian Demographic Research Institute School of Sociology and Political SciencesShanghai University99 Shangda RdShanghai 200444China Population Council New YorkUS International Institute for Applied Systems Analysis Wittgenstein Centre for Demography and Global Human Capital(IIASAOeAWUniversity of Vienna)LaxenburgAustria

From 1990 to 2019,stomach cancer posed a significant health burden in East Asia.The impact of stomach cancer deaths on life expectancy at birth in East Asian countries remains underexplored.This study quantifies the impact of stomach cancer on life expectancy(LE)and decomposes the age-specific contributions of this impact from 1990 to 2019 for East Asian countries.Using Global Burden of Disease data,we utilize potential gains in life expectancy(PGLEs)at birth to assess the impact by building cause-deleted life tables.The research decomposed age-specific contributions to the impact using Arriaga’s method.The findings reveal that stomach cancer deaths reduced approximately 0.35 to 1.02 years in LE at birth for males and 0.24 to 0.66 years for females in East Asian countries over the decades.The impact of stomach cancer on life expectancy in China,Japan,and South Korea converged before 2004 and then declined.A sudden drop characterized North Korea between 1995 and 2003.Notably,the patterns of age-specific contributions to the impact were heterogeneous.In China,Japan,and South Korea,the most impactful contribution in the PGLEs at birth shifted towards older age groups,while the pattern in North Korea showed limited changes.Focusing on consistent stomach cancer prevention policies could yield greater life expectancy gains,especially for older males.Despite rising life expectancy,nations with slower declines in stomach cancer mortality may face a more pronounced impact in the future.

关键词： stomach cancer Decomposition Life expectancy East Asia

BRAF mutation in multiple primary cancer with colorectal cancer and stomach cancer

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Gastroenterology Report 2013年第1期1卷 70-74页

作者： Seung-Hyun Lee Byung-Kwon Ahn Sung-Uhn Baek Hee-Kyung Chang Department of Surgery and Pathology Kosin University College of MedicineBusanKorea

Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers.The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer.Methods:BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer,synchronously or metachronously.Results:Mean age was 64.07 years(range:47–83 years).For the colorectal cancer,tumors were located at the sigmoid colon in eight patients(17.8%)and at the rectum in 22 patients(48.9%).Twenty-three patients(51.1%)had synchronous cancer.Four patients(8.9%)had family members with cancer.BRAF mutation was identified in three patients(6.7%).All three of these patients had metachronous cancers.The colorectal cancers were located in the sigmoid colon(1 patient)and the rectum(2 patients).Conclusions:BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer.With only BRAF gene study,it was not possible to identify any correlation with family history of colorectal cancer.Further study means considering other genes–MSI,MSH2,MLH1,MSH6.

关键词： multiple primary cancer colorectal cancer stomach cancer BRAF mutation

Environmental Risk Factors for stomach cancer in an African Setting about 193 Cases at the CHU Point G in Bamako/Mali

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Surgical Science 2021年第2期12卷 23-30页

作者： Souleymane Sanogo Drissa Traoré Mamadou Coulibaly Birama Togola Bréhima Bengaly Ousmane Ibréhima Touré Drissa Ouattara Bréhima Coulibaly Babou Ba Siaka Diallo Nouhoum Ongoiba Surgery B CHU Point G Bamako Mali USTTB Faculty of Medicine Bamako Mali Koutiala Regional Hospital Koutiala Mali

CHU (University Hospital Center) Point G: The department of surgery B is a surgical department of CHU Point G. The department is par excellence a reference department for cases of visceral surgery, cancer surgery, cardiovascular surgery, plastic and endocrinology surgery. As a reminder, the CHU Point G is the largest 3rd level referral hospital in Mali. Aim: To study the environmental risk factors of stomach cancer in the B surgery department of the Point G University Hospital in Bamako. Patients and Methods: We performed a cross-sectional study with retrospective collection from January 2008 to June 2018 (126 months). Results: We have identified 380 cases of digestive cancer, including 193 cases of stomach cancer or 50.79% of digestive cancers. The mean age of the patients was 57.21 ± 13 years. Male sex represented 55% (n = 106). Eating habits were dominated by the consumption of tô with potash (cereal paste) with 64.76% (n = 185). The main methods of preserving meat and fish were curing and smoking with 57.51% (n = 111). Chronic smoking was found in 24.35% (n = 47), alcohol + tobacco consumption in 2.59% (n = 5). The low socio-economic class represented 126 cases or 65.38%. Housewives and cultivators were respectively 37.82% (n = 73) and 227.97% (n = 54). 20.20% (n = 39) had a history of epigastric pain. Epigastralgia was the most common functional sign with 84.5% of cases (n = 169). An epigastric mass was found in 72 patients or 37.3%. Adenocarcinoma represented 97.4% (n = 188). Palliative surgery concerned the majority of our

关键词： stomach cancer Environmental Risk Factors African Setting CHU Point G