已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Impact of the PI3K-alpha inhibitor alpelisib on everolimus resistance and somatostatin receptor expression in an orthotopic pancreatic NEC xenograft mouse model

依维莫司 医学 神经内分泌肿瘤 安慰剂 内科学 肿瘤科 mTOR抑制剂的发现与发展 药理学 PI3K/AKT/mTOR通路 泌尿科 病理 生物 替代医学 细胞凋亡 生物化学
作者
Ajay-Mohan Mohan,Sonal Prasad,Fabian Schmitz-Peiffer,Catharina Lange,Mathias Lukas,Eva J. Koziolek,Jakob Albrecht,Daniel Messroghli,Ulrike Stein,Matthias Ilmer,Katharina Wang,Laura Schober,Astrid Reul,Julian Maurer,Juliane Friemel,Achim Weber,Richard A. Zuellig,Constanze Hantel,Ralph Fritsch,Martín Reincke,Karel Pacák,Ashley Grossman,Christoph J. Auernhammer,Felix Beuschlein,Winfried Brenner,Nicola Beindorff,Svenja Nölting
出处
期刊:Endocrine-related Cancer [Bioscientifica]
卷期号:31 (1) 被引量:1
标识
DOI:10.1530/erc-23-0041
摘要

The mechanistic target of rapamycin complex 1 (mTORC1) inhibitor everolimus is one of the few approved therapies for locally advanced and metastatic neuroendocrine tumours (NETs). However, after initial disease stabilisation, most patients develop resistance within 1 year. Our aim was to overcome resistance to everolimus by additional treatment with the PI3K-alpha inhibitor alpelisib in an everolimus-resistant orthotopic pancreatic neuroendocrine carcinoma xenograft mouse model. Female SCID mice underwent laparoscopic pancreatic transplantation of everolimus-sensitive (BON1KDMSO) or everolimus-resistant (BON1RR2) NET cells. Both groups were further divided into four treatment groups: placebo, everolimus, alpelisib, and everolimus + alpelisib (combination). Oral treatment was started at a tumour volume of approximately 140 mm3 and continued until 1900-2000 mm3, validated by weekly MRI. Somatostatin receptor expression and tumour viability were analysed by 68Ga-DOTATOC and 18F-FDG PET/CT. Everolimus resistance of the BON1RR2 tumours was confirmed. In the everolimus-sensitive group, everolimus alone, alpelisib alone, and combination treatment significantly prolonged survival, compared to placebo, while in the BON1RR2 group, only combination treatment significantly prolonged survival compared to placebo, but neither everolimus nor alpelisib alone. Placebo-treated everolimus-sensitive tumours grew more rapidly (median survival 45 days), compared to placebo-treated everolimus-resistant tumours (60 days). Within the everolimus-sensitive group, the combination-treated mice showed the longest median survival (52 days). Of all groups, the everolimus-resistant combination-treated group survived longest (69 days). Combination treatment with everolimus and alpelisib seems promising to overcome everolimus resistance in neuroendocrine neoplasms, and should be further examined in a clinical trial.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
零知识完成签到 ,获得积分10
刚刚
伽拉发布了新的文献求助10
6秒前
洸彦完成签到 ,获得积分10
8秒前
CipherSage应助G1997采纳,获得10
8秒前
Ethan完成签到 ,获得积分0
9秒前
9秒前
Rondab应助科研通管家采纳,获得10
10秒前
科研通AI2S应助科研通管家采纳,获得10
11秒前
11秒前
CipherSage应助科研通管家采纳,获得10
11秒前
Rondab应助科研通管家采纳,获得10
11秒前
Rondab应助科研通管家采纳,获得10
11秒前
SciGPT应助科研通管家采纳,获得10
11秒前
SciGPT应助科研通管家采纳,获得10
11秒前
11秒前
明钟达完成签到 ,获得积分10
14秒前
domingo发布了新的文献求助20
14秒前
HughWang完成签到,获得积分10
17秒前
嘟嘟豆806完成签到 ,获得积分10
19秒前
22秒前
火星完成签到 ,获得积分10
22秒前
24秒前
研友_Zlx3aZ发布了新的文献求助10
26秒前
认真的三问完成签到,获得积分20
28秒前
kyfbrahha完成签到 ,获得积分10
29秒前
29秒前
maleo发布了新的文献求助30
32秒前
domingo完成签到,获得积分10
33秒前
一直向前发布了新的文献求助10
33秒前
希望天下0贩的0应助Unicorn采纳,获得50
34秒前
toto完成签到 ,获得积分10
34秒前
宣灵薇完成签到,获得积分0
35秒前
35秒前
39秒前
大模型应助黎乐荷采纳,获得10
40秒前
福福发布了新的文献求助10
42秒前
cc完成签到 ,获得积分10
42秒前
大帅比完成签到 ,获得积分10
44秒前
44秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
Aktuelle Entwicklungen in der linguistischen Forschung 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989957
求助须知:如何正确求助?哪些是违规求助? 3532034
关于积分的说明 11256000
捐赠科研通 3270880
什么是DOI,文献DOI怎么找? 1805070
邀请新用户注册赠送积分活动 882252
科研通“疑难数据库(出版商)”最低求助积分说明 809216