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oxaliplatin-induced neuropathy and colo-rectal cancer patient's quality of life:Practical lessons from a prospective cross-sectional,real-world study

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World Journal of Clinical Cases 2022年第10期10卷 3101-3112页

作者： Iulian Prutianu Teodora Alexa-Stratulat Elena Octaviana Cristea Andrei Nicolau Diana Cornelia Moisuc Alina Alexandra Covrig Karina Ivanov Adina Emilia Croitoru Monica Ionela Miron Mihaela Ioana Dinu Anca Viorica Ivanov Mihai Vasile Marinca Iulian Radu Bogdan Gafton SC MNT Healthcare Europe SRL Iasi 700021Romania University of Medicine and Pharmacy Grigore T Popa Iasi Iasi 700483Romania Regional Oncology Institute Iasi Iasi 700483Romania Oral and Maxillo-facial Surgery University of Medicine and Pharmacy Grigore T Popa IasiIasi 700021Romania Department of Medical Oncology Fundeni Clinical InstituteBucuresti 022328Romania University of Medicine and Pharmacy“Grigore T Popa” Iasi 700021Romania Department of Surgery Department of Surgical OncologyUniversity of Medicine and Pharmacy“Grigore T Popa”Regional Institute of OncologyIasi 700021Romania

BACKGROUND Colon cancer is one the most common forms of cancer in both *** to important progress in the field of early detection and effective treatment,colon and rectal cancer survivors currently account for 10%of cancer survivors ***,the effects of anti-cancer treatments,especially oxaliplatinbased chemotherapy,on the quality of life(QoL)have been less *** the incidence of severe chemotherapy-induced neuropathy(CIPN)in clinical studies is below 20%,data from real-world studies is scarce,and CIPN is probably under-reported due to patient selection and the patients’fear that reporting side-effects might lead to treatment *** To determine the impact of CIPN on QoL in colorectal cancer patients with a recent history of oxaliplatin-based *** We performed a prospective cross-sectional study in two major Romanian oncology tertiary hospitals—the Regional Institute of Oncology Ia?i(Iasi,Romania)and the Fundeni Clinical Oncology Institute(Bucharest,Romania).All consecutive patients with colon or rectal cancer,undergoing oxaliplatin-based chemotherapy that consented to enroll in the study,were assessed by means of two questionnaires—the EORTC QQ-CR29(quality of life in colon and rectal cancer patients)and the QLQ-CIPN20(assessment of neuropathy).Several demographical,social,clinical and treatment data were also *** analysis was performed by means of SPSS *** student t test was used to assess the relationship between the QLQ-CIPN20 and QLQ-CR29 *** Meyer-curves were used to report 3-year progression-free survival(PFS)in patients that discontinued chemotherapy vs those that completed the recommended *** Of the 267 patients that fulfilled the inclusion criteria in the pre-specified time frame,101(37.8%)agreed to participate in the clinical *** the time of the enrolment in the study,over 50%of the patients had recently interrupted their oxaliplatin-based chemotherapy,mo

关键词： Colorectal cancer oxaliplatin Neuropathy Quality of Life Recurrence-free survival Cross-sectional study

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer

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World Journal of Gastroenterology 2009年第7期15卷 871-876页

作者： Tian-Jie Qin Gai-Li An Xin-Han Zhao Fang Tian Xiao-Hua Li Juan-Wen Lian Bo-Rong Pan Shan-Zhi Gu Department of Medical Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China Department of Oncology Cancer Institute Fourth Military Medical University Xi'an 710032 Shaanxi Province China Key Laboratory of Environment and Genes Related to Diseases Ministry of Education School of Medicine of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China

AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the ***:Sixty-four patients(median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative *** patient received at least two cycles of *** efficacy,side effects and patient survival were ***:The partial response(PR) rate was 43.8%(28/64).Stable disease(SD) rate was 47.9%(26/64),and disease progression rate was 15.6%(10/64).The clinical benefit rate(PR + SD) was 84.4%.The main toxicities were leukopenia(50.0%),nausea and vomiting(51.6%),diarrhea(50.0%),stomatitis(39.1%),polyneuropathy(37.5%) and hand-foot syndrome(37.5%).No grade 4 event in the entire cohort was *** median progression-free survival was 4 mo,median overall survival was 10 mo(95% CI:8.3-11.7 mo),and the 1-and 2-year survival rates were 38.1% and 8.2%,*** Karnofsky index,single metastatic lesion and response to the regimen indicated respectively good ***:oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC *** regimen has improved the survival moderately and merits further studies.

关键词： oxaliplatin Capecitabine Metastaticesophageal squamous cell cancer Survival analysis

Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin(Ⅳ) prodrug delivery and enhanced colorectal cancer therapy

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Chinese Chemical Letters 2024年第4期35卷 280-286页

作者： Wenjia Wang Xingyue He Xiaojie Wang Tiantian Zhao Osamu Muraoka Genzoh Tanabe Weijia Xie Tianjiao Zhou Lei Xing Qingri Jin Hulin Jiang State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Faculty of Pharmacy Kinki University HigashiosakaOsaka 577-8502Japan State Key Laboratory of Natural Medicines(SKLNM)and Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China School of Pharmacy Hangzhou Medical CollegeHangzhou 311399China College of Pharmacy Yanbian UniversityYanji 133002China

oxaliplatin(Oxa) is the first-line chemotherapeutic drug for the treatment of colorectal cancer(CRC). However, long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2(COX-2) and prostaglandin E2(PGE2), which can promote tumor metastasis. Moreover,high glutathione(GSH) levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa. Herein, an Oxa(Ⅳ) prodrug with anti-inflammatory properties(desmethyl naproxe, DN) and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles(designated DNPt@PPRI). The relesae of DN from DNPt@PPRI can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein,and also synergize with Oxa to inhibit tumor. More importantly, GSH depletion can reduce the detoxification of Oxa and further enhance chemotherapy-induced apoptosis. DNPt@PPRI have a good GSH depletion ability to enhance the sensitivity of Oxa, indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.

关键词： oxaliplatin Glutathione depletion Tetravalent platinum prodrug Synergistic therapy Colorectal cancer

Mechanism of Suppression on Proliferation of QGY Cell by oxaliplatin

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Chinese Journal of Cancer Research 2007年第4期19卷 263-268页

作者：何松左国庆张燕汤为学刘长安 Department of Gastroenterology The Second Clinical CollegeChongqing Medical University Department of Pathophysiology The Second Clinical College Chongqing Medical University Department of Hepatobiliary Surgery The Second Clinical College

Objective： To observe the effects of oxaliplatin（L-OHP） on proliferation of human hepatoma cell line QGY in vitro and to investigate the mechanism. Methods： The inhibition of proliferation in QGY cell was assayed by MTT-test. Morphologic changes were observed under light microscope and electronic microscope. Distribution of cell cycle and apoptosis were analyzed using flow cytometry. The expressions of cell cycle proteins and apoptosis-associated proteins were detected with immuno-histochemical technique. Results： oxaliplatin could inhibit the proliferation of QGY cells and the inhibition depended on the exposure time and dose. The cells showed morphologic changes of the early stage of apoptosis under the light microscope： the shrunk round cells, condensed cytoplasma and pycnosis of nucleus. Apoptotic cells and apoptotic body could be found under the transmission electronic microscope. The analysis of cell cycle indicated that oxaliplatin blocked cells at S and G2/M phases and the cells of G0/G1 phase reduced. When treated with oxaliplatin for 72h, the expressions of cyclin A and Bax were up-regulated, mutant type P53, Bcl-2 and Myc were down-regulated, and Fas was not changed. Conclusion： oxaliplatin could inhibit the proliferation of the hepatoma cell lines. Cells were blocked at S and G2/M phases. The apoptosis was related to the up-regulation of Bax and down-regulation of mutant type P53, Bcl-2 and Myc. oxaliplatin could not induce apoptosis through the Fas pathway.

关键词： oxaliplatin Hepatocellularcarcinoma Proliferation

oxaliplatin induced disseminated intravascular coagulation: A case report and review of literature

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World Journal of Gastrointestinal Oncology 2012年第7期4卷 181-183页

作者： Shweta Kurian Jessica Macintyre Muzammil Mushtaq Caio Max Rocha-Lima Yeon Ahn Division of Hematology Oncology Sylvester Comprehensive Cancer Center University of Miami Miami FL 33136 United States

oxaliplatin in combination with a fluoropyrimide is a treatment option for colorectal cancer patients in the adjuvant and metastatic settings. Very few hematological emergencies have been reported associated with oxaliplatin. These include autoimmune hemolytic anemia, thrombocytopenia and pancytopenia. We present a case report of a patient who developed hematuria and disseminated intravascular coagulation while receiving the second cycle of FOLFOX and bevacizumab for metastatic colon cancer.

关键词： oxaliplatin Disseminated intravascular coagulation Hematological emergencies Metastatic colon cancer Platelet count

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by oxaliplatin in Rats

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Chinese Journal of Integrative Medicine 2022年第9期28卷 833-839页

作者： WANG Feng-jiao SHI She WANG Yong-qiang WANG Ke FAN Shen-dong ZHANG Ya-nan FENG Chen-chen JU Zi-yong College of Acumox and Tuina Shanghai University of Traditional Chinese MedicineShanghai201203China Department of Anesthesiology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200120China Acupuncture Anesthesia Clinical Research Institute Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China

Objective:To study the effect of electroacupuncture(EA)on oxaliplatin-induced peripheral neuropathy(OIPN)in ***:Male Sprague-Dawley rats were equally divided into 3 groups using a random number table:the control group,the OIRN group,and the EA(OIPN+EA)group,with 10 rats in *** time courses of mechanical,cold sensitivity,and microcirculation blood flow intensity were *** morphology of the dorsal root ganglion(DRG)was observed by electron microscopic *** protein levels of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and the transient receptor potential(TRP)protein family in DRGs were assayed by Western ***:EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats(Poxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs(Poxaliplatin(P<0.01).In addition,the expression levels of Nrf2 and HO-1 were down-regulated,and the TRP protein family was over-expressed in the DRGs of OIPN rats(P<0.01).EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG(P<0.05 or P<0.01).Conclusion:EA may be a potential alternative therapy for OIPN,and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

关键词： electroacupuncture oxaliplatin peripheral neuropathy dorsal root ganglion nuclear factor-erythroid-2-related factor 2

Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells

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World Journal of Gastroenterology 2012年第7期18卷 646-653页

作者： Xiang-Liang Zhang An-Bin Hu Shu-Zhong Cui Hong-Bo Wei Department of Gastroin-testinal Surgery The Third Affiliated Hospital of Sun Yat-SenUniversity Guangzhou 510630 Guangdong Province China Department of General Surgery The First AffiliatedHospital of Sun Yat-Sen University Guangzhou 510080 Guang-dong Province China Department of Abdominal Surgery AffiliatedTumor Hospital of Guangzhou Medical College Guangzhou510095 Guangdong Province China

AIM： To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.

关键词： Colorectal cancer oxaliplatin Thermoche-motherapy Mitochondrial apoptotic pathway

Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2

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Acta Pharmaceutica Sinica B 2019年第5期9卷 1008-1020页

作者： Lu Chen Le Chen Zhiyuan Qin Jinxiu Lei Sheng Ye Kui Zeng Hua Wang Meidan Ying Jianqing Gao Su Zeng Lushan Yu Institute of Drug Metabolism and Pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Paediatric Intensive Care Unit the Children's HospitalZhejiang University School of MedicineHangzhou310003China Department of Urology Cancer Hospital of Zhejiang ProvinceHangzhou310022China

Renal cell carcinoma(RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that mi R-489-3 p and mi R-630 suppress OCT2 expression by directly binding to the OCT2 30-UTR. Meanwhile, via 786-O-OCT2-mi RNAs stable expression cell models, we found that mi RNAs could repress the classic substrate 1-methyl-4-phenylpyridinium(MPP+), fluorogenic substrate N,N-dimethyl-4-(2-pyridin-4-ylethenyl) aniline(ASP+), and oxaliplatin uptake by OCT2 both in vitro and in xenografts. In 33 clinical samples, mi R-489-3 p and mi R-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and q PCR validation. The increased binding of c-Myc to the promoter of pri-mi R-630, responsible for the upregulation of mi R-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that mi R-489-3 p and mi R-630 function as oncotherapy-obstructing micro RNAs by directly targeting OCT2 in RCC.

关键词： OCT2 mi RNA Renal cell carcinoma Epigenetic regulation oxaliplatin

LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway

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World Journal of Gastroenterology 2011年第2期17卷 181-190页

作者： Jie Liu xue-Qiong Fu Wei Zhou Hong-Gang Yu Jie-Ping Yu He-Sheng Luo Institute of Gastroenterology and Hepatology Wuhan University Medical School Wuhan430060 Hubei Province China Department ofGastroenterology Renmin Hospital of Wuhan University Wu-han 430060 Hubei Province China

AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide *** cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling *** blotting and immuno-precipitation were used to examine protein expression and recruitment,*** factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift *** mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in *** MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB ***294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) *** vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer *** enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.

关键词： Gastric cancer oxaliplatin Phosphatidylinositol 3’-kinase/Akt pathway Death receptor pathway Apoptosis LY294002