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Meta-analysis on inoperable pancreatic cancer: A comparison between gemcitabine-based combination therapy and gemcitabine alone

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World Journal of Gastroenterology 2006年第43期12卷 6973-6981页

作者： De-Rong Xie Han-Lin Liang Yu Wang Shuan-Shuan Guo Qiong Yang Department of Oncology The Second Affiliated Hospital Sun Yat-Sen University Guangzhou 510120 Guangdong Province China Department of C-hemotherapy Zhongshan People's Hospital Sun Yat-Sen University Zhoushan 528403 Guangdong Province China Department of Oncology Jiangmen Central Hospital Jiangmen 529000 Guangdong Province China

AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through meta- analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity. RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04, 95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD = 0.04, 95% CI 0.01-0.07, P = 0.02), CBR (RD = 0.10, 95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD = 0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95% CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05, 95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD = 0.03, 95% CI 0.00-0.05, P = 0.02). CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimalpatients with APCa as compared with GEM alone.

关键词： Chemotherapy Pancreatic cancer Metaanalysis gemcitabine

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第3期14卷 207-215页

作者： Wei HONG Kai WANG Yi-ping ZHANG Jun-yan KOU Dan HONG Dan SU Wei-min MAO Xin-min YU Fa-jun XIE Xiao-jian WANG Department of Medical Oncology Zhejiang Cancer Hospital Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology Department of Respiratory Medicine the Second Affiliated HospitalSchool of MedicineZhejiang University Department of Medical Oncology Hangzhou Cancer Hospital Institute of Immunology School of MedicineZhejiang University

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT）（41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

关键词： Non-small cell lung cancer Single nucleotide polymorphism Methylenetetrahydrofolate reductase gemcitabine Excision repair cross-complementation group 1

Folate-chitosan-gemcitabine core-shell nanoparticles targeted to pancreatic cancer

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Chinese Journal of Cancer Research 2013年第5期25卷 527-535页

作者： Jiahua Zhou Junying Wang Qian Xu Shi Xu Jin Wen Zeqian Yu Detong Yang Department of General Surgery Zhongda HospitalSchool of MedicineSoutheast University Ministry of Education Key Laboratory of Environmental Medicine and Engineering Southeast University

Objective：Human pancreatic cancer is one of the most common clinical *** effect of comprehensive treatment based on surgery is *** effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic *** study aimed to investigate the effects of folate receptor （FR）-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic ***：In this study,the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical *** uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FA-Chi-Gem nanoparticles on COLO357 cells was evaluated by MTT ***,the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline ***：The expression of FR in COLO357 was the highest among the six pancreatic cancer cell *** FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic ***,the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA *** proliferation of COLO357 was significantly inhibited by FA-Chi-Gem *** PEG-FA-ICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts,while non-targeted nanoparticles were mainly in normal liver ***-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts （PEG-FA-Gem-Chi ***,t=22.950,P=0.000）.Conclusions：PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.

关键词： Pancreatic cancer folate receptor targeted nanoparticle gemcitabine

Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1148-1162页

作者： Pearl Moharil Zhuoya Wan Apurva Pardeshi Jiang Li Haozhe Huang Zhangyi Luo Sanjay Rathod Ziqian Zhang Yuang Chen Bei Zhang Christian A.Fernandez Jingjing Sun Song Li Center for Pharmacogenetics Department of Pharmaceutical ScienceSchool of PharmacyUniversity of PittsburghPA 15261USA

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of ***,most reported polymeric systems have sizes above100 nm,which limits effective extravasation into tumors that are poorly vascularized and have dense *** will,in turn,limit the overall effectiveness of the subsequent uptake by tumor cells via active *** this study,we combined the passive targeting via ultra-small-sized gemcitabine(GEM)-based nanoparticles(NPs)with the active targeting provided by folic acid(FA)conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages(TAMs).We developed an FAmodified prodrug carrier based on GEM(PGEM)to load doxorubicin(DOX),for co-delivery of GEM and DOX to *** co-delivery system showed small particle size of~10 nm in *** ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release *** FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor(FR),but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of ***,in vivo,systemic delivery of FAPGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer *** study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2,which was selectively expressed on ***,targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

关键词： Folic acid gemcitabine Polymeric micelles Breast cancer Dual targeting Tumor associated macrophages Ultrasmall nanocarrier Doxorubicin

Nedaplatin/gemcitabine Versus Carboplatin/gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

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Chinese Journal of Cancer Research 2012年第2期24卷 97-102页

作者： Jin-ji Yang Qing Zhou Ri-qiang Liao Yi-sheng Huang Chong-rui Xu Zhen Wang Bin-chao Wang Hua-jun Chen Yi-long Wu Division of Pulmonary Oncology Guangdong Lung Cancer InstituteCancer CenterGuangdong General Hospital&Guangdong Academy of Medical SciencesGuangzhou 510080China

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

关键词： Non-small cell lung cancer Chemotherapy Nedaplatin Carboplatin gemcitabine Squamous cell carcinoma

RRM1 gene expression in peripheral blood is predictive of shorter survival in Chinese patients with advanced non-small-cell lung cancer treated by gemcitabine and platinum

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第3期12卷 174-179页

作者： Lin-run WANG Guo-bing ZHANG Jian CHEN Jun LI Ming-wei LI Nong XU Yang WANG Jian-zhong SHEN TU4 Department of Pharmacy the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Department of Infectious Diseases the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Department of Medical Oncology the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China Clinical Laboratory the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

Objective:To evaluate the predictive values of gene expressions of ribonucleotide reductase M1(RRM1) and breast cancer susceptibility gene 1(BRCA1) in peripheral blood from Chinese patients with non-small-cell lung cancer(NSCLC) treated with gemcitabine plus ***:Forty Chinese patients with advanced NSCLC were recruited and received gemcitabine 1200 mg/m 2 on Days 1 and 8 plus carboplatin AUC 5 on Day ***1 and BRCA1 expression levels in peripheral blood were detected by quantitative reverse transcription-polymerase chain reaction(RT-PCR) .Kaplan-Meier survival curve and log-rank test were performed to evaluate the correlation between gene expression and overall survival for these ***:No correlation was observed between gene expression of RRM1 and that of BRCA1(P>0.05) ,but there was a strong correlation between the expression of RRM1 and the response to chemotherapy(P=0.003) .Subjects with low RRM1 expression levels in peripheral blood had longer sur-vival time than those with high RRM1 expression levels(16.95 vs.12.76 months,log-rank 3.989,P=0.046) .However,no significant association between BRCA1 expression levels and survival time was found(16.80 vs.13.77 months,log-rank 0.830,P=0.362) .Conclusions:Patients with low RRM1 expression levels in peripheral blood have a greater response to chemotherapy and longer survival *** NSCLC patients with low RRM1 expression levels may benefit from gemcitabine plus platinum ***1 mRNA expression in peripheral blood could be used to predict the prognosis of NSCLC treated by gemcitabine and platinum.

关键词： gemcitabine Non-small-ce Ribonucleotide reductase M1 (RRM1) Breast cancer susceptibility gene 1 (BRCA1) ung cancer (NSCLC) Gene expression

MSX2 overexpression inhibits gemcitabine-induced caspase-3 activity in pancreatic cancer cells

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World Journal of Gastroenterology 2005年第43期11卷 6867-6870页

作者： Shin Hamada Kennichi Satoh Kenji Kimura Atsushi Kanno Atsushi Masamune Tooru Shimosegawa Division of Gastroenterology

AIM： To evaluate the effect of MSX2 on gemcitabineinduced caspase-3 activation in pancreatic cancer cell line Panc-1. METHODS： Using V5-tagged MSX2 expression vector, stable transfectant of MSX2 was generated from Panc-i cells （Px14 cells）. Cell viability under gemcitabine administration was determined by MTF assay relative to control cell line （empty-vector transfected Panc-1 cells; P-3EV cells）. Hoechst staining was used for the detection of apoptotic cell. Activation of caspase-3 was assessed using Western blotting analysis and direct measurement of caspase-3 specific activities. RESULTS： MSX2 overexpression in Panc-1 cells resulted in decreased gemcitabine-induced caspase-3 activation and increased cell viability under gemcitabine treatment in Px14 cells. CONCLUSION： MSX2 exerts repressive effects on gemcitabine-induced apoptotic pathway. This novel apoptosis-regulating function of MSX2 may provide a new therapeutic target for pancreatic cancer.

关键词： MSX2 Caspase-3 gemcitabine

Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2005年第5期6卷 446-450页

作者：王临润黄明珠徐农申屠建中刘健蔡捷 First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China

To determine the pharmacokinetics of gemcitabine (2′,2′-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m2 per min (1200 mg/m2, two hours infusion) and carboplatin, and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimnation half life (t1/2) (10.67±3.38 min), area under the curve (AUC) (7.55±1.53 (μg·h)/ml), and clearance (CL) (3940.05±672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.

关键词： gemcitabine Non-small-cell lung cancer Pharmacokinetics

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

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World Journal of Gastroenterology 2008年第34期14卷 5311-5315页

作者： Hisato Igarashi Tetsuhide Ito Ken Kawabe Terumasa Hisano Yoshiyuki Arita Toyoma Kaku Ryoichi Takayanagi Department of Medicine and Bioregulatory Science Graduate School of Medical ScienceKyushu University

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, ***: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

关键词： Advanced pancreatic cancer Chemoradio-therapy gemcitabine Radiosensitizer Tumor marker