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Involvement of substance P and the NK-1 receptor in pancreatic cancer

World Journal of Gastroenterology 2014年第9期20卷 2321-2334页

作者： Miguel Muoz Rafael Coveas Virgen del Rocío University Hospital Research Laboratory on Neuropeptides (IBIS) 41013 Seville Spain Institute of Neurosciences of Castilla y León (INCYL) Laboratory of Neuroanatomy of the Peptidergic Systems (Lab 14) University of Salamanca 37007 Salamanca Spain

Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,***,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer *** peptide substance P(SP)has a widespread distribution throughout the *** binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor *** is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer *** these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.

关键词： Pancreas Substance P neurokinin-1 receptor antagonists Apoptosis Antitumor Angiogenesis Metastasis Pancreatic cancer

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Validation of different personalized risk models of chemotherapy-induced nausea and vomiting:results of a randomized,double-blind,phase III trial of fosaprepitant for cancer patients treated with high-dose cisplatin

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Cancer Communications 2023年第2期43卷 246-256页

作者： Yuanyuan Zhao Bing Zhao Gang Chen Yinlan Chen Zijun Liao Haiming Zhang Weineng Feng Yinyin Li Heng Weng Weidong Li Yuefen Zhou Biyong Ren Yanda Lu Jianhua Chen Zhenteng Liu Zhenzhong Su Wenliang Wang Li Zhang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.Chin Department of Day Ward First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangP.R.China Department of Medical Oncology Jiangxi Cancer HospitalNanchangJiangxiP.R.China Department of Medical Oncology Shaanxi Provincial Cancer HospitalXi’anShaanxiP.R.China Department of Medical Oncology The First People Hospital of XiangtanXiangtanHunanP.R.China Department of Medical Oncology The First People Hospital of FoshanFoshanGuangdongP.R.China Department of Medical Oncology Shenyang Tenth People’s HospitalShenyangLiaoningP.R.China Respiratory Medicine Fuzhou Pulmonary Hospital of FujianFuzhouFujianP.R.China Department of Medical Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouGuangdongP.R.China Department of Medical Oncology The Central Hospital of LishuiLishuiZhejiangP.R.China Department of Medical Oncology Chongqing Three Gorges Central HospitalChongqingP.R.China Department of Medical Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikouHainanP.R.China Department of Medical Oncology Hunan Province Tumor HospitalChangshaHunanP.R.China Institute of Materia Medica Luoxin Pharmaceutical Group Co.LtdShanghaiP.R.China

Background:Highly emetogenic chemotherapy induces emesis in cancer patients without *** purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting(CINV)in patients with solid malignant tumors,determine risk factors and externally validate different personalized risk models for ***:This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin *** primary endpoint was complete response(CR)during the overall phase(OP)with a non-inferiority margin of 10.0%.Logistic regression modelswere used to assess the risk factors ofCRand no *** validate the personalized risk models,the accuracy of the risk scoring systems was determined by measuring the specificity,sensitivity and area under the receiver operating characteristic(ROC)curve(AUC),while the predictive accuracy of the nomogram was measured using concordance index(C-index).Results:A total of 720 patients were randomly *** during the OP in the fosaprepitant group was not inferior to that in the aprepitant group(78.1%vs.77.7%,P=0.765)with a between-group difference of 0.4%(95%CI,-5.7%to 6.6%).Female sex,higher cisplatin dose(≥70 mg/m2),no history of drinking and larger body surface area(BSA)were significantly associated with *** AUC for the acute and delayed CINV risk indexes was 0.68(95%CI:0.66-0.71)and 0.66(95%CI:0.61-0.70),respectively,and the C-index for nomogram CINV prediction was 0.59(95%CI,0.54-0.64).Using appropriate cutoff points,the three models could stratify patients with high-or low-risk *** nausea and CR rate were significantly higher in the low-risk group than in the high-risk group(P1).Conclusions:Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cis

关键词： aprepitant chemotherapy-induced nausea and vomiting clinical trial fosaprepitant neurokinin-1 receptor antagonists nomogram nomogram personalized risk model

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