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First evidence of olaparib maintenance therapy in patients with newly diagnosed homologous recombination deficient positive/BRCA wild-type ovarian cancer:real-world multicenter study

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Frontiers of Medicine 2024年第6期18卷 1026-1034页

作者： Jing Li Youguo Chen Mian He Xiaoxiang Chen Hao wen Yu Kang Kaijiang Liu Ge Lou Xipeng Wang qinglian wen Li Wang Zhongqiu Lin Department of Gynaecological Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou510120China Department of Obstetrics and Gynecology The First Affiliated Hospital of Soochow UniversitySuzhou215006China Department of Obstetrics and Gynecology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China Department of Gynecological Oncology Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing211166China Department of Gynecological Oncology Fudan University Shanghai Cancer CenterShanghai200032China Department of Gynecological Oncology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai215311China Department of Gynecological Oncology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200025China Department of Gynecological Oncology Harbin Medical University Cancer HospitalHarbin150081China Department of Obstetrics and Gynecology Xinhua Hospital Affiliated to Shanghai Jiao Tong University of MedicineShanghai200092China Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhou646099China Department of Cancer Biology Immunotherapy The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhou450003China

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer,its effectiveness in patients without BRCA mutations remains poorly *** study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such *** real-world data from 11 high-volume tertiary care centers in China,a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian *** primary objective was 1-year progression-free survival *** was also *** patients with a median age of 54 years were included,and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency(HRD).The 1-year PFS rate was 75.2%(95%CI,63.4 to 89.2),and the median PFS was 21.0 months(95%CI,13.8 to 28.2).All the patients received olaparib at a starting dose of 300 mg twice daily,and none experienced serious adverse events(AEs).Eight(16%)patients had dose adjustment,but none discontinued olaparib treatment due to *** provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.

关键词： adverse events maintenance therapy olaparib ovarian cancer progression-free survival

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Conditional reprogramming:next generation cell culture

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1360-1381页

作者： Xiaoxiao Wu Shengpeng Wang Mingxing Li Jing Li Jing Shen Yueshui Zhao Jun Pang qinglian wen Meijuan Chen Bin Wei Parham Jabbarzadeh Kaboli Fukuan Du Qijie Zhao Chi Hin Cho Yitao Wang Zhangang Xiao Xu Wu Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhou 646000China South Sichuan Institute of Translational Medicine Luzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Oncology and Hematology Hospital(T.C.M)Affiliated to Southwest Medical UniversityLuzhou 646000China Center of Radiation Oncology Hospital(T.C.M)Affiliated to Southwest Medical UniversityLuzhou 646000China Department of Oncology the Affiliated Hospital of Southwest Medical UniversitySouthwest Medical UniversityLuzhou 646000China College of Pharmaceutical Science&Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals Zhejiang University of TechnologyHangzhou 310014China School of Biomedical Sciences Faculty of Medicinethe Chinese University of Hong KongHong KongChina

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming(CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR cocultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase(ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

关键词： culture epithelium programming

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Clinical features of patients with HER2-positive breast cancer and development of a nomogram for predicting survival

Clinical features of patients with HER2-positive breast canc...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Yu Fan Yu Wang Lijia He Saber Imani qinglian wen The affiliated hospital of southwest medical university

Background:Different estrogen receptor(ER) and progesterone receptor(PR) expression patterns have important biological and therapeutic implications in patients with human epidermal growth factor receptor 2(HER2)-positive breast ***,little is known about hormone receptor(HR)-positive and triple-positive subtypes,making therapy selection and survival prognosis *** study investigated the clinical characteristics and nomogram-predicted survival of patients with HER2-positive breast *** and methods:Data on patients with HER2-positive breast cancer were retrieved from the Surveillance,Epidemiology,and End Results *** were carried out between single HR-positive and double HR-positive/double HR-negative subtypes.A nomogram-based model of predicted outcomes was ***:This cohort study included 34 819 patients with breast cancer(34 606 women and 213 men).Single HR-positive and double HR-positive/double HR-negative subtypes showed distinct clinicopathological *** Cox regression analysis showed that patients with ER-positive/PR-negative/HER2-positive [hazard ratio(HR)= 1.24;95%confifidence interval(CI):1.14-1.39],ER-negative/PR-positive/HER2-positive(HR= 1.56;95% CI:1.23-1.97),and ER-negative/PR-negative/HER2-positive(HR= 1.56;95% CI:1.43-1.70) subtypes had worse breast cancer-specifific survival than patients with the triple-positive *** clinical parameters were included as prognostic factors in the nomogram:age,sex,race,grade,histology type,bone,brain,liver,and lung metastasis,TNM(tumor-node-metastasis) staging,and molecular *** C-index was 0.853(95%CI:0.845-0.861).Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 3-year and 5-year ***:Signifificant differences in survival rates were observed between single HR-positive and double HR-positive/double HR-negative subtypes.A nomogram accurately predicted

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CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer:An Integrated Analysis

CLIP4 Shows Putative Tumor Suppressor Characteristics in Bre...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Yu Fan Lijia He Yu Wang Shaozhi Fu Yunwei Han Juan Fan qinglian wen The affiliated hospital of southwest medical university

Background:CAP-Gly domain containing linker protein family member 4(CLIP4) plays an important role in ***,its expression,prognostic value,and biological effect in breast cancer remain ***:Data on patients diagnosed with breast cancer were retrieved from the TCGA0002RCA and other public omics *** expression profifile of CLIP4 was analyzed using Oncomine,bc-GenExMiner,and *** prognostic value of CLIP4 was determined by Kaplan-Meier Plotter and Human Protein *** of genes co-expressed with CLIP4 and potential mechanism analyses were performed using UALCAN,STRING,Metascape,and *** epigenetic characteristics of CLIP4 were determined by DiseaseMeth and ***:CLIP4 was downregulated and its expression was negatively correlated with estrogen receptor(ER),progesterone receptor(PR),human epidermal growth factor receptor type 2(HER2) status,Nottingham prognostic index(NPI),and Scarff-Bloom-Richardson(SBR) grade in breast cancer,whereas it was positively linked to basal-like and triple negative breast cancer *** expression of CLIP4 was related with poor *** the analysis of genes co-expressed with CLIP4,GSEA showed that the Hedgehog(Hh),JAK-STAT,ERBB,Wnt signaling pathway,cell adhesion molecules,and pathways in cancer were dissimilarly enriched in the CLIP4 expression high *** of the genetics and epigenetics of CLIP4 indicated that its expression was negatively correlated with DNA ***:Methylated CLIP4 may be a novel prognostic and therapeutic biomarker for breast cancer.

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重组人血管内皮抑素联合紫杉醇不同时序给药降低肺癌移植瘤小鼠血清中VEGF和HIF-1α的水平及其意义

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肿瘤 2016年第3期36卷 264-271页

作者：李萌丁瑞麟文庆莲泸州医学院附属医院肿瘤科四川泸州646000

目的：研究重组人血管内皮抑素（recombinant human endostatin,rhendostatin）联合紫杉醇（paclitaxel,PTX）不同时序给药对肺癌移植瘤小鼠血清中血管内皮生长因子（vascular endothelial growth factor,VEGF）和缺氧诱导因子1α（hypoxia inducible factor-1α,HIF-1α）水平的影响及其意义,并探讨rh-endostatin联合PTX给药的最佳时序。方法：建立肺癌Lewis细胞的C57/BL小鼠皮下移植瘤模型,并随机分为对照组（腹腔注射0.9%Na Cl,第1~14天）、单药PTX组（腹腔注射PTX,第1天）、单药rh-endostatin组（腹腔注射rh-endostatin,第1~14天）、联合组1[腹腔注射rh-endostatin（第1~14天）＋PTX（第1天）]、联合组2[腹腔注射rh-endostatin（第1~14天）＋PTX（第4天）]和联合组3[腹腔注射rh-endostatin（第1~14天）＋PTX（第7天）]。各组给药后,动态测量小鼠移植瘤体积,免疫组织化学法检测移植瘤组织中微血管密度（microvascular density,MVD）以及可反映微血管周细胞量的α平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）表达水平,ELISA法检测小鼠血清中VEGF和HIF-1α的水平,高效液相色谱法检测移植瘤组织中PTX的浓度。结果：从用药的第2天开始,rh-endostatin单药组及各联合组血清中VEGF水平均明显降低（P值均〈0.05）;从用药的第5天开始,rh-endostatin单药组及各联合组血清中HIF-1α水平也明显降低（P值均〈0.05）;在用药的第5天及第8天,rh-endostatin单药组及各联合组肿瘤组织中MVD较对照组明显降低（P值均〈0.05）,而α-SMA表达水平较对照组明显升高（P值均〈0.05）;在3个联合组中,联合组2与对照组的MVD以及VEGF、HIF-1α和α-SMA表达水平差异最明显（P值均〈0.05）。联合组2的小鼠移植瘤组织中PTX浓度明显高于另外2个联合组（P值均〈0.05）,移植瘤体积也明显小于另外2个联合组（P值均〈0.05）。结论：血清VEGF和HIF-1α水平可作为监测肿瘤微血管正常化的有效指标。在VEGF水平下降初期,rh-endostatin联合PTX用药可提高肿瘤组织中局部PTX的浓度,增加PTX的抗肿瘤效应。

关键词：肺肿瘤内皮抑素类紫杉醇血管内皮生长因子缺氧诱导因子1,α亚基

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兔VX2鼻咽移植瘤模型建立的研究现状

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中国比较医学杂志 2016年第6期26卷 83-87页

作者：胡月文庆莲张莉西南医科大学附属医院肿瘤科四川泸州646000 西南医科大学附属医院核医学科四川泸州646000

总结和介绍了兔VX2鼻咽移植瘤模型的制作方法,并对模型制备的各个环节进行了分析和方法改进的探讨,以期为医学实验研究提供良好的动物模型。

关键词：兔 VX2 鼻咽肿瘤模型,动物

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宫颈癌中DNMT1的高表达与其不良生存结局的相关性

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实用医学杂志 2018年第17期34卷 2921-2924页

作者：罗舒陈非郭黔文庆莲西南医科大学附属医院肿瘤科四川泸州646000

目的探讨DNMT1在宫颈癌中的表达与宫颈癌生存结局的相关性。方法以102例接受初级治疗的宫颈癌患者为研究对象,采用免疫组化检测DNMT1的表达,以DNMT1阳性细胞百分比及其强度表示DNMT1的表达程度,以Cox比例风险模型评估DNMT1的表达程度与... 详细信息

目的探讨DNMT1在宫颈癌中的表达与宫颈癌生存结局的相关性。方法以102例接受初级治疗的宫颈癌患者为研究对象,采用免疫组化检测DNMT1的表达,以DNMT1阳性细胞百分比及其强度表示DNMT1的表达程度,以Cox比例风险模型评估DNMT1的表达程度与调整相关协变量后存活率之间的关系。结果与正常宫颈组织及癌旁组织相比,宫颈癌组织中DNMT1的表达明显升高,DNMT1阳性细胞比例升高,DNMT1强度评分升高,并与生存率差异显着相关(P=0.041 1)。结论宫颈癌组织中DNMET1的表达较高,其高表达与宫颈癌的不良预后相关。

关键词：宫颈癌 DNMT1 生存结局

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安罗替尼联合5-氟尿嘧啶抑制结肠癌的增殖和血管生成

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遵义医科大学学报 2020年第2期43卷 195-201页

作者：杨茜文庆莲西南医科大学附属医院肿瘤科四川泸州646000

目的探讨安罗替尼联合5-氟尿嘧啶对结肠癌CT26细胞的增殖、侵袭、凋亡及血管生成的影响。方法在体外实验,应用MTT法、Transwell法以及流式细胞术检测安罗替尼组(4μmol/L)、5-氟尿嘧啶组(5μg/mL)以及联合组(安罗替尼4μmol/L+5-氟尿嘧... 详细信息

目的探讨安罗替尼联合5-氟尿嘧啶对结肠癌CT26细胞的增殖、侵袭、凋亡及血管生成的影响。方法在体外实验,应用MTT法、Transwell法以及流式细胞术检测安罗替尼组(4μmol/L)、5-氟尿嘧啶组(5μg/mL)以及联合组(安罗替尼4μmol/L+5-氟尿嘧啶5μg/mL)对结肠癌CT26细胞的增殖、侵袭及凋亡的影响。然后,建立结肠癌CT26细胞的皮下移植瘤模型,随机分为4组(n=12):NS组,安罗替尼组(2 mg/kg),5-氟尿嘧啶组(20 mg/kg),联合组(安罗替尼2 mg/kg+5-氟尿嘧啶20 mg/kg),探究各组对结肠癌皮下移植瘤的抗肿瘤作用,观察各组带瘤小鼠的肿瘤生长情况,采用免疫组化检测各组肿瘤组织中Ki-67的表达水平和微血管密度。结果体外细胞实验结果显示联合组对细胞增殖活性的抑制率明显高于单药安罗替尼组或5-FU组(P<0.05),且联合组对结肠癌CT26细胞侵袭能力的抑制作用最大(P<0.05);此外,流式细胞术检测发现联合组使细胞凋亡率显著增高(P<0.05)。皮下移植瘤模型实验结果显示联合组能明显抑制小鼠皮下移植瘤的生长(P<0.05)。与生理盐水组、单药安罗替尼或5-FU组相比,联合组药物作用能显著降低肿瘤组织中的Ki-67阳性表达率和微血管密度(P<0.05)。结论安罗替尼联合5-氟尿嘧啶能显著抑制结肠癌的增殖和侵袭,促进细胞的凋亡,并抑制小鼠肿瘤组织中细胞的增殖及血管的生成,具有良好的抗肿瘤作用。

关键词：安罗替尼 5-氟尿嘧啶结肠癌增殖抗血管生成

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18F-脱氧葡萄糖PET/CT联合胰腺肿瘤标志物在诊断早期可切除胰腺癌术后复发转移中的应用价值

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重庆医科大学学报 2019年第11期44卷 1469-1473页

作者：向张强杨茜倪来超文庆莲西南医科大学附属医院肿瘤科

目的:探讨18F-脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射型计算机断层显像(positron emission computed tomography,PET/CT)联合常见血清胰腺肿瘤标志物在诊断早期可切除胰腺癌术后复发转移中的价值及相关性。方法:回顾性... 详细信息

目的:探讨18F-脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)正电子发射型计算机断层显像(positron emission computed tomography,PET/CT)联合常见血清胰腺肿瘤标志物在诊断早期可切除胰腺癌术后复发转移中的价值及相关性。方法:回顾性分析53例早期可切除胰腺癌患者术后怀疑复发转移而行PET/CT和胰腺肿瘤标志物检测的相关检查资料,探究两者联合检查用于诊断早期可切除胰腺癌术后复发转移的价值及相关性。结果:联合组[PET/CT+糖类抗原19-9(carbohydrate antigen 19-9,CA19-9)+糖类抗原242(carbohydrate antigen 242,CA242)+糖类抗原50(carbohydrate antigen 50,CA50)]在诊断早期可切除胰腺癌术后复发转移的灵敏度、特异度、准确率、阳性预测值(positive predictive value,PPV)及阴性预测值(negative predictive value,NPV)分别为97.83%、85.71%、96.23%、97.83%、85.71%。其中联合组灵敏度分别高于单独CA19-9组、单独CA242组、单独CA50组,差异均具有统计学意义(P<0.05)。联合组准确率分别高于单独PET/CT组、单独CA19-9组、单独CA242组、单独CA50组,差异均具有统计学意义(P<0.05)。血清CA19-9水平与PET/CT中病灶的最大标准化摄取值(maximum standardized uptake value,SUVmax)呈正相关(r=0.583,P=0.018)。结论:18F-FDG PET/CT检查联合常见胰腺肿瘤标志物检测在诊断早期可切除胰腺癌术后复发转移中具有较高的灵敏度、准确率及阳性预测值,能尽早诊断胰腺癌术后出现的复发转移,使患者及时得到进一步治疗。

关键词：胰腺癌复发转移 PET/CT 胰腺肿瘤标志物

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早期宫颈癌复发的分子生物学机制研究进展

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中国医药科学 2013年第10期3卷 39-40,42页

作者：杨茂楠文庆莲泸州医学院附属医院四川泸州646000

近年来随着宫颈癌普查的普及,早期宫颈癌患者数量有所增加。但早期宫颈癌患者经治疗后也有复发现象。大量的研究已表明早期宫颈癌复发是一个多因素、多过程、多种基因蛋白分子参与的复杂演变过程,本文就早期宫颈癌复发的分子生物学机制... 详细信息

近年来随着宫颈癌普查的普及,早期宫颈癌患者数量有所增加。但早期宫颈癌患者经治疗后也有复发现象。大量的研究已表明早期宫颈癌复发是一个多因素、多过程、多种基因蛋白分子参与的复杂演变过程,本文就早期宫颈癌复发的分子生物学机制研究进展做一综述。

关键词：早期宫颈癌复发分子生物学

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