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Clinical efficacy and safety evaluation of Buzhongyiqi pills(补中益气丸)on appetite improvement in patients with colorectal cancer receiving chemotherapy:a pilot randomized cross-over clinical trial

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Journal of Traditional Chinese Medicine 2024年第6期44卷 1254-1267页

作者： QIAN Jianan XU Yan HU Hongyi zhao aiguang Department of Gastroenterology Longhua HospitalShanghai University of Traditional Chinese Medicine2.Institute of Digestive DiseasesLonghua HospitalShanghai University of Traditional Chinese Medicine3.Department of OncologyLonghua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Gastroenterology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

OBJECTIVE: To evaluate the clinical efficacy and safety of Buzhongyiqi pills(BZYQP, 补中益气丸) in improving the appetite of patients with colorectal cancer(CRC) receiving chemotherapy. TRIAL DESIGN: A pilot, randomized, single-blind crossover clinical trial was conducted on diagnosed stage II-IV CRC patients receiving chemotherapy. METHODS: Patients were randomly assigned to either the BZYQP-placebo or placebo-BZYQP groups. The BZYQP-placebo group received BZYQP for 1-2 d before the first cycle of chemotherapy and continued until the end of the third cycle. A 7-day washout followed, after which they received a placebo until the end of the sixth cycle. The placebo-BZYQP group followed the opposite treatment order. The oral dose of BZYQP and placebo was ten pills three times daily. A total of 12 visit points were scheduled in this study, with each visit point carried out before and after each of the six cycles of chemotherapy. The Simplified Nutrition Appetite Questionnaire(SNAQ), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30, version 3.0), and the National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE, V5.0) were used to evaluate patient appetite, quality of life, and drug safety. RESULTS: Totally 62 patients completed the study, and baseline characteristics were balanced between the BZYQP-placebo and placebo-BZYQP groups. The primary outcome, as assessed by SNAQ scores, demonstrates a statistically significant difference between the two groups during the first three cycles of chemotherapy, with the mean SNAQ score of the BZYQP-placebo group consistently higher than that of the placebo-BZYQP group from V1(P < 0.001). After the washout period, the SNAQ score of the BZYQP-placebo group decreased from V7, and the difference in SNAQ scores between the two groups gradually became more significant after the intersection at V9. Secondary outcomes showed that during the first three cycles of che

关键词： colorectal neoplasms appetite quality of life adverse events pilots cross-over studies randomized controlled trials Buzhongyiqi pills

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基于胃癌关键基因的中药抗肿瘤研究现状分析

中医杂志 2022年第23期63卷 2239-2245页

作者：王芮沈雨苗赵爱光上海中医药大学附属龙华医院上海市200032

目的分析以胃癌关键基因为治疗靶点的中药在胃癌防治中的研究现状。方法在GEO数据库中下载胃癌基因表达谱芯片数据,经筛选后确定GSE54129和GSE64916两个数据集,以“P<0.05,Log2FC≥1”为截断值进行肿瘤组织与正常组织的差异表达基因筛选... 详细信息

目的分析以胃癌关键基因为治疗靶点的中药在胃癌防治中的研究现状。方法在GEO数据库中下载胃癌基因表达谱芯片数据,经筛选后确定GSE54129和GSE64916两个数据集,以“P<0.05,Log2FC≥1”为截断值进行肿瘤组织与正常组织的差异表达基因筛选,利用韦恩图取两个数据集的交集,进行基因本体论(GO)分析、京都基因与基因组百科全书(KEGG)通路富集分析及差异表达基因的蛋白互作(PPI)网络分析,采用Cytoscape(3.8.2版本)软件计算得出的关键基因,在Coremine Medical数据库中对关键基因进行检索,在“traditional Chinese medicine”条目中得到以关键基因作为治疗靶点的中药。对得到的中药进行频次统计,选择前5味中药,在中文及外文数据库中对其在胃癌中的相关研究进行文献检索。将检索到的文献分为临床研究、网络药理学分析、数据挖掘/处方经验、基础实验,对研究现状进行总结。结果韦恩图取交集后得到两个数据集有150个共同的差异表达基因,富集到的生物功能与通路主要有PI3K/AKT通路、上皮细胞转移、胶原蛋白细胞外基质等。利用String绘制PPI网络,进一步在Cytoscape中根据自由度大小选出前10位的关键基因:CDKN2A、SPP1、CTGF、C3、CST3、APOB、GC、IL18、CCND1、CD34。应用Coremine medical数据库分析得到治疗关键基因靶点的中药,对检索到的中药进行频次统计,出现频次最高的前五味中药分别为黄芪(与9个基因有关),白花蛇舌草、淫羊藿、三七(各与4个基因有关),菝葜(与3个基因有关)。外文数据库未检索到相关文献,于2022年2月20日在中文CNKI数据库分别以“胃癌”“胃恶性肿瘤”and“黄芪”“白花蛇舌草”“淫羊藿”“三七”“菝葜”进行检索,仅中药黄芪有临床研究,共49篇;网络药理学分析中黄芪有8篇,白花蛇舌草3篇,其他中药未检索到;数据挖掘/处方规律研究中黄芪21篇,白花蛇舌草4篇,其他中药未检索到;基础实验中黄芪35篇,白花蛇舌草15篇,三七6篇,淫羊藿3篇,菝葜4篇,其中黄芪与三七有一项基础实验研究重合。临床研究多涉及黄芪提取物注射液联合其他治疗对患者临床疗效及不良反应的影响;网络药理学分析中,包括的药对有黄芪-党参/白术/莪术/女贞子、白花蛇舌草-半枝莲等;数据挖掘多集中在黄芪、白花蛇舌草两味中药;基础实验研究多以药物单体为主。结论治疗胃癌组织与正常组织的关键差异表达基因靶点的中药主要有黄芪、白花蛇舌草、三七、淫羊藿、菝葜,目前以黄芪的相关研究最多。

关键词：胃癌基因芯片生物信息分析关键基因

The Mechanism pf Weichang'an in Inducing Apoptosis of Gastric Cancer SGC7901 Cells

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Chinese Medicine and Natural Products 2021年第1期1卷 13-23页

作者： CHEN Weixi NIU Yaofei zhao aiguang Department of Oncology Longhua Hospital Affiliated to Shanghai University of Chinese MedicineShanghai 200032China Department of Oncology Henan Province Hospital of Chinese MedicineZhengzhouHenan 450002China Infection ICU Henan Provincial People's HospitalZhengzhouHenan 450003China

Objective:To investigate the effect of Chinese medicine Compound Weichang'an(胃肠安)for invig-orating the spleen on apoptosis of gastric cancer SGC7901 cells and its possible ***:The gas-trie cancer SGC-7901 cells were divided into different mass concentration groups(0 mg·L^(-1),500 mg·L^(-1)1000 mg·L^(-1),1500 mg·L^(-1),2000 mg·L^(-1)).CCK8 and monoclonal test were applied to detect prolifera-tion ability;comet assay was used to detect DNA *** DCFH-DA fluorescent labeling,the level of ROS activity was detected by flow cytometer;after AnnexinV-FTC/PI double labeling,the proportion of apoptotic ellls was detected by flow cytometer;after JC-1 staining,the mi tochondri almembrane potential was detected by flow cytometer;after FTTC-DEVD-FMK staining,the ratio of Caspase activity was detected by flow ***:Weichang an inhibited cell proliferation and reduced cell colony formation in a time-dose-dependent manner;the results of comet electrophoresis showed that Weichang'an could induce DNA damage in gastric cancer cells;com-pared with control *** ratio of Weichang'an's intervention with the apoptosis of gastric cancer cells in-creased(P<0.05),the mitochondrial membrane potential decreased(P<0.05),the activity of Caspase3 and Caspase9 increased(P<0.05),and the intracellular ROS level increased(P<0.05).Among them,the effect of Weichang'an treatment group(1000 mg·L^(-1))was the most ***:Weichang'an has an inhibi-tory effect on the proliferation of gastric cancer SGC7901 cells and can induce cell *** mechanism may be related with the ROS-mediated pathway of mitochondrial apoptosis and DNA damage.

关键词： Weichang'an gastric cancer SGC7901 cells mitochondrial apoptosis DNA damage

The Chinese Herbal Formula Weichang’an Reduces the Proliferation of Human Gastric Cancer Cells via Mitochondrial Apoptosis

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Chinese Medicine and Natural Products 2024年第3期4卷 117-125页

作者： Weixia Chen Yaofei Niu Bin Chen aiguang zhao Department of Oncology Henan Province Hospital of Traditional Chinese MedicineZhengzhouHenanChina Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Infection Henan Provincial People’s Hospital/Zhengzhou University People’s HospitalZhengzhouHenanChina Department of Oncology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

Objective The aim of the study was to investigate the effects of Chinese herbal formula Weichang’an(WCA)on the proliferation and mitochondria-mediated apoptosis of human gastric cancer *** Cell Counting Kit-8(CCK8)was used to evaluate the antiproliferative activity ofWCA on MKN45 cells;Giemsa staining was used to investigate cell colony formation;flow cytometry was used to analyze cell cycle,apoptosis rate,and caspases activation;and Hoechst staining was used to analyze the morphology of cell *** mitochondrial membrane potential was analyzed by both flow cytometric measurements and fluorescence *** blot was used to analyze the protein levels of pro-caspase-3,Bcl-2,Bax,and ***45 cells were subcutaneously injected into the right forelimb of 16 nude mice to establish the tumor xenograft model,and a total of 12 nude mouse tumor xenograft models were successfully *** nude mice were divided into the control group and the WCA-treated *** two groups received normal saline and WCA treatment at 35.49 g/kg by a single daily oral gavage for 21 *** body weight and tumor size of the nude mice were measured twice a *** ultrastructural changes of subcutaneous tumors were observed by a transmission electron *** WCA can suppress cell proliferation and colony *** can also induce changes in the mitochondrial membrane potential and increase the activities of caspases-3,caspases-8,and caspases-9 in MKN45 *** induced S-phase arrest and apoptosis in MKN45 cells,and decreased the expression levels of antiapoptotic proteins Bcl-2 and Bcl-X in MKN45 cells,while increasing the expression levels of the proapoptotic proteins Bax and pro-caspase-3 compared with the control *** inhibited the growth of a xenografted MKN45 tumor in nude mice,and the protein levels of Bax and pro-caspase-3 were significantly increased,while Bcl-X and Bcl-2 were reduced compared with the control *** differences are

关键词： gastric cancer Chinese herbal formula Weichang’an mitochondrial apoptosis

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中药汤剂及主要新剂型的研究现状

世界中医药 2014年第3期9卷 396-399页

作者：陈彬赵爱光上海中医药大学附属龙华医院上海200032

通过分析中药汤剂(传统煎煮与机器煎煮)、中药配方颗粒剂以及中药微粉的优缺点,表明中药新煎法的使用及新剂型的开发需要进一步深入研究。

关键词：中药汤剂机器煎煮中药配方颗粒剂中药微粉

胃肠安对人胃癌细胞侵袭转移及RUFY3、MAPKs通路的影响

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中医杂志 2019年第7期60卷 592-596页

作者：李佳陈伟霞李朝燕赵爱光上海中医药大学附属龙华医院上海市200023 河南省郑州市中医院

目的探讨胃肠安抑制胃癌侵袭转移的作用及可能作用机制。方法采取细胞增殖实验筛选胃肠安进行实验的药物浓度。实验分为空白组,胃肠安高、低剂量组,5-氟尿嘧啶(5-FU)组。细胞培养24 h后胃肠安高、低剂量组用拟筛选浓度的胃肠安100μl进... 详细信息

目的探讨胃肠安抑制胃癌侵袭转移的作用及可能作用机制。方法采取细胞增殖实验筛选胃肠安进行实验的药物浓度。实验分为空白组,胃肠安高、低剂量组,5-氟尿嘧啶(5-FU)组。细胞培养24 h后胃肠安高、低剂量组用拟筛选浓度的胃肠安100μl进行干预,5-FU组加入32 mg/L 5-FU注射液100μl,空白组给予无血清培养基100μl。采用CCK8法检测细胞增殖的变化,划痕实验和Transwell侵袭实验检测胃癌细胞迁移和侵袭能力;采用免疫印迹法检测RUN和FYVE结构域蛋白3 (RUFY3)、磷酸化细胞外信号调节激酶(p-ERK)、促分裂原活化蛋白激酶(MEK)、磷酸化促分裂原活化蛋白激酶(p-MEK)、Twist1、E-钙粘蛋白、波形蛋白、N-钙粘蛋白、血管内皮生长因子(VEGF)、基质金属蛋白酶2 (MMP2)、基质金属蛋白酶9 (MMP9)蛋白表达水平。结果筛选出500 mg/L和1000 mg/L浓度的胃肠安为胃肠安低、高剂量组给药量。给药48 h时胃肠安高、低剂量组和5-FU组细胞迁移率均明显低于空白组(P <0. 01)。胃肠安高剂量组、5-FU组穿膜细胞数显著低于空白组和胃肠安低剂量组(P <0. 01)。胃肠安高、低剂量组侵袭抑制率分别为54. 11%、7. 65%,5-FU组侵袭抑制率为47. 88%。与空白组比较,胃肠安低剂量组p-ERK、Twist1蛋白表达降低,E-钙粘蛋白表达增加(P <0. 05);胃肠安高剂量组RUFY3、p-ERK、p-MEK、Twist1、N-钙粘蛋白及波形蛋白表达降低,E-钙粘蛋白表达增加(P <0. 05)。与胃肠安低剂量组比较,胃肠安高剂量组RUFY3、p-MEK、N-钙粘蛋白表达降低更明显(P <0. 05)。结论胃肠安可抑制胃癌的侵袭转移,并且以1000 mg/L浓度效果最好,其机制可能是通过调控RUFY3、MAPKs通路来调节侵袭转移相关蛋白和抑制胃癌细胞上皮-间充质转化。

关键词：胃肠安胃癌侵袭转移 RUN和FYVE结构域蛋白3 丝裂原活化蛋白激酶

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秦皮乙素抗肿瘤作用及机制

中华中医药学刊 2019年第7期37卷 1620-1623页

作者：李朝燕丁亚杰李佳赵爱光上海中医药大学附属龙华医院肿瘤科

秦皮乙素是一种具有良好抗肿瘤活性的中药提取活性成分,特别是秦皮乙素的有效性和低毒性,使其在肿瘤治疗中的应用越来越广泛。研究表明秦皮乙素对肺癌、胃癌、肝癌、胰腺癌、肠癌、前列腺癌、乳腺癌、黑色素瘤、脑胶质瘤、骨髓瘤、白血... 详细信息

秦皮乙素是一种具有良好抗肿瘤活性的中药提取活性成分,特别是秦皮乙素的有效性和低毒性,使其在肿瘤治疗中的应用越来越广泛。研究表明秦皮乙素对肺癌、胃癌、肝癌、胰腺癌、肠癌、前列腺癌、乳腺癌、黑色素瘤、脑胶质瘤、骨髓瘤、白血病等肿瘤均有治疗作用,可以抑制细胞增殖、诱导细胞凋亡、阻滞细胞周期、抑制肿瘤转移、抑制血管生成、增强免疫力和增敏减毒等作用,这些研究为秦皮乙素的临床应用及药物开发提供实验基础。

关键词：秦皮乙素抗肿瘤机制实验研究

胃肠安对人胃癌细胞SGC-7901原位移植瘤细胞增殖和凋亡的影响

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胃肠病学 2006年第6期11卷 336-339页

作者：郑嘉岗赵爱光顾缨尤圣富赵海磊唐莱娣上海中医药大学附属龙华医院消化内科 200032 上海中医药大学附属龙华医院肿瘤科上海中医药大学附属龙华医院科研实验中心

背景:以健脾类中药为基础的复方胃肠安可抑制人胃癌细胞SGC-7901裸小鼠皮下移植瘤细胞的增殖,并诱导细胞凋亡,提高进展期胃癌的3年生存率。目的:通过观察胃肠安对人胃癌细胞裸小鼠原位移植瘤生长和凋亡的影响,探讨其抑制肿瘤的作用机制... 详细信息

背景:以健脾类中药为基础的复方胃肠安可抑制人胃癌细胞SGC-7901裸小鼠皮下移植瘤细胞的增殖,并诱导细胞凋亡,提高进展期胃癌的3年生存率。目的:通过观察胃肠安对人胃癌细胞裸小鼠原位移植瘤生长和凋亡的影响,探讨其抑制肿瘤的作用机制。方法:以高效液相色谱(HPLC)法监测复方胃肠安制剂的稳定性;采用胃小囊法,予45只雄性BALB/c-nu/nu裸小鼠接种人胃癌细胞SGC-7901移植瘤模型,造模第28天,选出扪及胃部肿块直径为3mm左右的裸小鼠共43只,随机分为胃肠安组(14只)、5-氟尿嘧啶(5-FU)组(14只)和对照组(15只);采用免疫组化SP法检测增殖细胞核抗原(PCNA)的表达;采用缺口末端标记(TUNEL)法检测细胞凋亡指数。结果:胃肠安组原位瘤抑制率为40.8%,肝转移率(7.7%)和总转移率(30.8%)显著低于对照组(50.0%和71.4%)(P<0.05);胃肠安组原位移植瘤PCNA阳性率和总阳性率(51.0%±11.4%和60.4%±13.3%)显著低于对照组(61.6%±11.6%和74.4%±7.9%)(P=0.0287和P=0.0029);胃肠安组细胞凋亡指数(17.3%±8.9%)显著高于对照组(7.8%±3.0%)(P=0.0010)。结论:复方胃肠安可抑制人胃癌细胞裸小鼠原位移植瘤的生长和转移,并可抑制人胃癌细胞原位移植瘤的细胞增殖和诱导凋亡。

关键词：中草药胃肠安胃肿瘤增殖细胞核抗原细胞凋亡肿瘤转移

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刺槐素抗肿瘤作用分子机制的研究进展

中华中医药学刊 2021年第5期39卷 53-56页

作者：李朝燕张光涛韩晨赵爱光上海中医药大学附属龙华医院上海200032 上海中医药大学附属岳阳中西医结合医院上海200437

刺槐素是从中药太子参、野菊花、藿香、刺槐等植物中提取的一种天然黄酮类化合物,因其药理作用广泛而受到科学工作者的关注与研究,近年来的研究发现其具有抗肿瘤的作用。随着分子生物学技术的应用,国内外对于刺槐素抗肿瘤作用机制的研... 详细信息

刺槐素是从中药太子参、野菊花、藿香、刺槐等植物中提取的一种天然黄酮类化合物,因其药理作用广泛而受到科学工作者的关注与研究,近年来的研究发现其具有抗肿瘤的作用。随着分子生物学技术的应用,国内外对于刺槐素抗肿瘤作用机制的研究逐渐向细胞分子水平深入,研究表明刺槐素对肺癌、胃癌、肝癌、肠癌、前列腺癌、乳腺癌、白血病等恶性肿瘤均具有治疗作用,可抑制肿瘤细胞增殖,诱导肿瘤细胞自噬及凋亡,抑制肿瘤细胞侵袭迁移和血管生成,调节免疫及逆转多药耐药等。通过对刺槐素抗肿瘤功效及分子机制层面的分析,探讨刺槐素的抗肿瘤作用,以阐明其具体作用机制,为抗肿瘤药物的研发提供参考。

关键词：刺槐素抗肿瘤机制实验研究综述