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IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU yongqian shu YINGWEI WANG WEN QIU CHENHUI ZHAO Department of Immunology Nanjing Medical UniversityNanjing210000China Key Laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains *** the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and *** investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to ***,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and ***,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all ***,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

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血管生成拟态在胃癌研究和治疗中的研究进展

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中国肿瘤生物治疗杂志 2024年第6期31卷 621-625页

作者：耿茜(综述) 束永前(审阅) 南京医科大学第一附属医院肿瘤科江苏南京210029 南京医科大学附属常州第二人民医院肿瘤科江苏常州213000

血管生成拟态(VM)是一种独立于内皮细胞的血管样结构,通常存在于需要血管生长的实体肿瘤中。VM与肿瘤细胞的增殖、侵袭、转移及胃癌患者的不良预后密切相关。VM的存在可能是胃癌患者抗血管生成药物耐药的原因之一,抗血管生成同时靶向VM... 详细信息

血管生成拟态(VM)是一种独立于内皮细胞的血管样结构,通常存在于需要血管生长的实体肿瘤中。VM与肿瘤细胞的增殖、侵袭、转移及胃癌患者的不良预后密切相关。VM的存在可能是胃癌患者抗血管生成药物耐药的原因之一,抗血管生成同时靶向VM治疗将有望成为胃癌治疗的新方向。

关键词：血管生成拟态胃癌抗血管生成靶向治疗

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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang shuang Tong Shiqing Chen Xing Li yongqian shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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Estrogen and its signaling pathway in non-small cell lung cancer(NSCLC)

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Journal of Nanjing Medical University 2009年第4期23卷 217-223页

作者： Ruitong Xu yongqian shu Department of Oncology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Lung cancer is the most common cancer in the world. It is a highly lethal disease in women and men, and new treatments are urgently needed. Several studies have implicated a role of estrogens and estrogen receptors in lung cancer progression. This review will investigate the biological significance of estrogens in lung cancer cells, the expression and molecular mechanisms of estrogen receptors（ER α and ER β, elucidate the prognostic significance of estrogens and their receptors in lung carcinomas and provide new options for patients afflicted with lung malignancies.

关键词： lung cancer estrogen estrogen receptor EGFR

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Sequential transcatheter arterial chemoembolization,three-dimensional conformal radiotherapy,and high-intensity focused ultrasound treatment for unresectable hepatocellular carcinoma patients

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The Journal of Biomedical Research 2012年第4期26卷 260-267页

作者： Shengfa Ni Lingxiang Liu yongqian shu Department of Oncology the First Affiliated HospitalNanjing Medical UniversityNanjingJiangsu 210029China

The purpose of this study was to evaluate the outcome of patients with unresectable hepatocellular carcinoma（HCC） treated by sequential therapy of transcatheter arterial chemoembolization（TACE）,three-dimensional conformal radiotherapy（3-DCRT） and high-intensity focused ultrasound（HIFU）.From October,2005 to September,2010,120 patients with unresectable HCC received the sequential treatments of several courses of TACE followed in 2-4 weeks by 3-DCRT and then a single session of HIFU with a curative *** median tumor irradiation dose was 40 *** response,toxicity and overall survival rate were *** factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis or multivariate *** 120 HCC patients were followed up by the last follow-up *** these patients,hepatic toxicities due to treatment were notable in 9 *** bleeding after the overall treatment occurred in 2 cases,leukopenia of grade III was detected in 1 case,radiation-induced liver disease（RILD） was observed in 2 patients,and first-and second-degree skin burn around the HIFU treatment zone were observed in 2 patients and 1 patient,*** 120 patients,23,83 and 14 cases achieved partial response,stable disease and progressive disease,*** overall survival rates at 1 year,3 years and 5 years were 70%,35% and 15%,respectively,with a median survival time of 26 *** Child-Pugh liver function grading and radiation dose were determined to be independent predictors for overall survival revealed by the multivariate *** is concluded that the sequential therapy of TACE,3-DCRT and HIFU is a promising therapeutic regimen for unresectable HCC.

关键词： transcatheter arterial chemoembolization(TACE) three-dimensional con-formal radiotherapy(3DCRT) high-intensity focused ultrasound(HIFU) hepatocellular carcinoma

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Research on the effects of CD137 signaling on the function of CD3^-CD56^+NK cells

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Journal of Nanjing Medical University 2009年第1期23卷 10-14页

作者： Yu Zhang Songwen Ju yongqian shu Cancer Biotherapy Center the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Objective： To investigate the effects of CD137 signaling on the regulation of CD3-CD56＋NK cells function. Methods： CD3 CD56＋NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects of CD 137 signaling on the function of CD3-CD56＋NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-I expression on CD3-CD56＋NK cells were analyzed by flow cytometry. Results： CD137 was expressed on activated CD3-CD56＋NK cells. The CD137 mAb enhanced the ability of CDB-CD56＋NK cells to kill lung cancer cells（A549）; Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells, and blockade of NKG2D and LFA-1 dramatically attenuated CD3CD56＋NK cytolysis of A549 cancer cells. Conclusion： CD 137 signaling increases the ability of CD3-CD56＋NK cells to kill cancer cells via up- regulating the expression of NKG2D and LFA-1.

关键词： CD137 CD3CD56+NK cells signal

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MiR-503 regulates cisplatin resistance of human gastric cancer cell lines by targeting IGF1R and BCL2

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Chinese Medical Journal 2014年第12期127卷 2357-2362页

作者： Wang Tongshan Ge Gaoxia Ding Yin Zhou Xin Huang Zebo Zhu Wei shu yongqian Liu Ping Department of Oncology First Affiliated Hospital of Nanjing Medical University NanjingJiangsu 210029China Department of Clinical Laboratory First Affiliated Hospital of Nanjing Medical University NanjingJiangsu 210029China State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjingJiangsu 210093China Department of Oncology Jiangsu Province HospitalNanjingJiangsu 210029China

Background Studies have shown that the drug resistance of gastric cancer cells can be modulated by abnormal expression of microRNAs （miRNAs）.We investigated the role of miR-503 in the development of cisplatin resistance in human gastric cancer cell *** MiR-503 expression was measured by quantitative real-time *** （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） and clonogenic assays were used to examine changes in cell viability and the drug resistance phenotype of cancer cells associated with upregulation or downregulation of the miRNA.A dual-luciferase activity assay was used to verify target genes of ***,Western blotting analysis,and a flow cytometric apoptosis assay were used to elucidate the mechanism by which miR-503 modulates drug resistance in cancer *** MiR-503 was significantly downregulated in gastric cancer tissues and several gastric cancer cell ***,downregulation of miR-503 in the cisplatin （DDP）-resistant gastric cancer cell line SGC7901/DDP was concurrent with the upregulation of insulin-like growth factor-1 receptor （IGF1R） and B-cell lymphoma 2 （BCL2） expression compared with the parental SGC7901 cell *** in vitro drug sensitivity assay showed that overexpression of miR-503 sensitized SGC7901/DDP cells to *** luciferase activity of reporters driven by IGF1R and BCL2 3＇-untranslated regions in SGC7901/DDP cells suggested that IGF1R and BCL2 were both direct target genes of *** miR-503 expression in SGC7901/DDP cells reduced expression of the target proteins,inhibited proliferation,and sensitized the cells to DDP-induced *** Our findings suggest that hsa-miR-503 modulates cisplatin resistance of human gastric cancer cells at least in part by targeting IGF1R and BCL2.

关键词： miR-503 cisplatin resistance insulin-like growth factor-1 receptor B-cell lymphoma 2 gastric cancer

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A meta-analysis of caspase-8-652 6N del polymorphism and digestive tract cancer risk

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The Journal of Biomedical Research 2019年第3期33卷 173-180页

作者： Haina Du Guoxin Song Mingzhi Fang yongqian shu Xin Zhao Lingjun Zhu Department of Oncology the Third Affiliated Hospital of Nanjing University of T.C.M Departments of Pathology the First Affiliated Hospital of Nanjing Medical University Departments of Oncology the First Affiliated Hospital of Nanjing Medical University Departments of Pneumology the First Affiliated Hospital of Nanjing Medical University

Caspase-8(CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism(-652 6 N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer *** evaluate the association between the CASP8-652 6 N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6 N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model(del/del vs. ins/ins: OR= 0.82, 95%CI= 0.72-0.95;del/ins vs. ins/ins: OR = 0.92,95%CI = 0.87-0.97;dominant model(del/ins + del/del vs. ins/ins: OR = 0.91,95%CI =0.87-0.96, recessive model: del/del vs. del/ins + ins/ins: OR = 0.85, 95%CI = 0.75-0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models,except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8-652 6 N del polymorphism and reduced digestive cancer risk, especially among Asians and populationbased studies.

关键词： caspases-8 polymorphism digestive tract cancer risk

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Prognostic significance of metastatic lymph nodes ratio in patients with gastric adenocarcinoma after curative gastrectomy

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Chinese Medical Journal 2014年第10期127卷 1874-1878页

作者： Zhang Meiling Wang Jian Shi Wei Chen Wenjiao Li Wei shu yongqian Liu Ping Lu Kaihua Department of Oncology First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu 210029 China Cancer Center of Nanjing Medical University Nanjing Jiangsu210029 China

Background We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio （the ratio between metastatic lymph nodes and total dissected lymph nodes,MLNR） in patients with gastric adenocaminoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric *** From January 2005 to December 2010,1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were *** particular,lymph node metastasis was not present in 515 *** number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease *** survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier *** The overall 5-year survival rate was 54％ in this *** analysis revealed that age category,macroscopic appearance,histological grade,tumor size,depth of primary tumor invasion,number of metastatic lymph nodes,metastatic lymph nodes ratio,tumor,nodes,metastasis-classification （TNM） stage and status of lymphovascular,and vessel invasion have significant impact on *** number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival （P ＜0.001）.However,in multivariate analyses,only the metastatic lymph nodes ratio was identified to be an independent prognostic factor （P ＜0.001）.The number of removed lymph nodes in node-negative was a strong prognostic factor of survival,the more lymph nodes dissected,the better the *** The metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph *** number of removed lymph nodes miaht be an important proanostic fact

关键词： gastric adenocarcinoma lymph nodes prognosis

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Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer

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Journal of Nanjing Medical University 2009年第6期23卷 392-397页

作者： Yongmei Yin Yiting Geng Xiaodong Li Xiaoli Hu Xiaofeng Chen Wei Li yongqian shu Department of Oncology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Objective： To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods： Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results： None of the patients achieved a complete response （CR）, while 15 patients achieved a partial remission （PR） and 17 experienced a stable disease （SD）. Thirteen patients continued to have a progressive disease （PD）. The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash （53.3%） and diarrhea （33.3%）. Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion： Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.

关键词： gefitinib non-small cell lung cancer (NSCLC) first-line treatment

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