检索结果-南通市图书馆

Impact of kras mutation and PTEN expression on cetuximab-treated colorectal cancer

World Journal of Gastroenterology 2010年第46期16卷 5881-5888页

作者： Fang-Hua Li,Zhuang-Hua Li,Hui-Yan Luo,Miao-Zhen Qiu,Yu-Hong Li,Rui-Hua Xu,State Key Laboratory of Oncology in Southern China,Department of Medical Oncology,Sun YatSen University Cancer Center,Guangzhou 510060,Guangdong Province,China Fang-Hua Li,Department of Medical Oncology,Shengli Oil Field Central Hospital,Dongying 257034,Shandong Province,China Lin Shen,Department of GI Oncology,Peking University School of Oncology,Beijing Cancer Hospital and Institute,Beijing 100142,China Hui-Zhong Zhang,State Key Laboratory of Oncology in Southern China,Department of Pathology,Sun Yat-Sen University Cancer Center,Guangzhou 510060,Guangdong Province,China State Key Laboratory of Oncology in Southern China Department of Medical Oncology Sun Yat-Sen University Cancer Center Guangzhou 510060 Guangdong Province China. xurh@***

AIM:To investigate the prognostic value of kras mutation,and phosphatase and tensin (PTEN) expression in Chinese metastatic colorectal cancer metastatic colorectal cancer (mCRC) patients treated with ***:Ninety Chinese mCRC patients treated with cetuximab were evaluated for kras mutation and PTEN protein expression by DNA sequencing of codons 12 and 13 and immunohistochemistry,*** then selected 61 patients treated with cetuximab,either in combination with chemotherapy,or alone as a second-line or third-line regimen to assess whether kras mutation or PTEN protein expression is associated with the response and the survival time of mCRC patients treated with ***:kras mutation was found in 30 (33.3%) tumor samples from the 90 patients,and positive PTEN expression was detected in 58 (64.4%) of the 90 *** the 61 patients who were treated with cetuximab as a second-line or third-line regimen,the resistance to cetuximab was found in 22 patients with kras mutation and in 39 patients without kras mutation,with a response rate of 4.5% and 46.1% respectively (P=0.001),a shorter median progression-free survival (PFS) time of 14 ± 1.3 wk and 32 ± 2.5 wk respectively (P kras mutation and PTEN expression analysis showed that the PFS and OS time of patients with two favorable prognostic factors were longer than those of patients with one favorable prognostic factor or no favorable prognostic factor (P kras mutation and PTEN protein expression are significantly corr

关键词： Cetuximab Metastatic colorectal cancer kras mutation Phosphatase and tensin protein expression

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

kras mutation-induced EndMT of brain arteriovenous malformation is mediated through the TGF-β/BMP-SMAD4 pathway

引用

Stroke & Vascular Neurology 2023年第3期8卷 197-206,I0006-I0027页

作者： Hongyuan Xu Ran Huo Hao Li Yuming Jiao Jiancong Weng Jie Wang Zihan Yan Junze Zhang Shaozhi Zhao Qiheng He Yingfan Sun Shuo Wang Yong Cao Department of Neurosurgery Beijing Tiantan HospitalCapital medical universityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina Beijing Neurosurgical Institute Capital Medical UniversityBeijingChina

Objective Somatic kras mutations have been identified in the majority of brain arteriovenous malformations(bAVMs),and subsequent in vivo experiments have confirmed that kras mutation in endothelial cells(ECs)causes AVMs in mouse and zebrafish *** previous study demonstrated that the krasG12D mutant independently induced the endothelial-mesenchymal transition(EndMT),which was reversed by treatment with the lipid-lowering drug ***,the underlying mechanisms of action were *** We used human umbilical vein ECs(HUVECs)overexpressing the krasG12D mutant for Western blotting,quantitative real-time PCR,and immunofluorescence and wound healing assays to evaluate the EndMT and determine the activation of downstream *** of SMAD4 by RNA interference was performed to explore the role of SMAD4 in regulating the *** ECs expressing the krasG12D mutant were obtained to verify the SMAD4 ***,we performed a coimmunoprecipitation assay to probe the mechanism by which lovastatin affects *** HUVECs infected with krasG12D adenovirus underwent the *** growth factor beta(TGF-β)and bone morphogenetic protein(BMP)signalling pathways were activated in the krasG12D-mutant HUVECs and ECs in bAVM *** down SMAD4 expression in both krasG12D-mutant HUVECs and ECs in bAVM tissues inhibited the *** attenuated the EndMT by downregulating p-SMAD2/3,p-SMAD1/5 and acetylated SMAD4 expression in krasG12D-mutant *** Our findings suggest that the krasG12D mutant induces the EndMT by activating the ERK-TGF-β/BMP-SMAD4 signalling pathway and that lovastatin inhibits the EndMT by suppressing TGF-β/BMP pathway activation and SMAD4 acetylation.

关键词： kras SMAD4 inhibited

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

kras mutation:from undruggable to druggable in cancer

引用

Signal Transduction and Targeted Therapy 2021年第12期6卷 3466-3485页

作者： Lamei Huang Zhixing Guo Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-Sen University Cancer CenterGuangzhou 510060P.R.China

Cancer is the leading cause of death worldwide,and its treatment and outcomes have been dramatically revolutionised by targeted *** the most frequently mutated oncogene,Kirsten rat sarcoma viral oncogene homologue(kras)has attracted substantial *** understanding of kras is constantly being updated by numerous studies on kras in the initiation and progression of cancer ***,kras has been deemed a challenging therapeutic target,even“undruggable”,after drugtargeting efforts over the past four ***,there have been surprising advances in directly targeted drugs for kras,especially in kras(G12C)inhibitors,such as AMG510(sotorasib)and MRTX849(adagrasib),which have obtained encouraging results in clinical ***,AMG510 was the first drug-targeting kras(G12C)to be approved for clinical use this *** review summarises the most recent understanding of fundamental aspects of kras,the relationship between the kras mutations and tumour immune evasion,and new progress in targeting kras,particularly kras(G12C).Moreover,the possible mechanisms of resistance to kras(G12C)inhibitors and possible combination therapies are summarised,with a view to providing the best regimen for individualised treatment with kras(G12C)inhibitors and achieving truly precise treatment.

关键词： kras precise truly

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Targeting kras G12C mutations in colorectal cancer

引用

Gastroenterology Report 2023年第1期11卷 4-13页

作者： Ming-He Zhao Ai-Wen Wu Key Laboratory of Carcinogenesis and Translational Research Ministry of EducationUnit IIIGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijingP.R.China

With the advent of Kirsten rat sarcoma viral oncogene homologue G12C(kras G12C)inhibitors,RAS is no longer considered *** the suppression of RAS,new therapeutic approaches have been ***,current clinical studies have indicated therapeutic resistance after short-lived tumour *** to preclinical studies,this might be associated with acquired genetic alterations,reactivation of downstream pathways,and stimulation for upstream *** this review,we aimed to summarize current approaches for combination therapy to alleviate resistance to kras G12C inhibitors in colorectal cancer with a focus on the mechanisms of therapeutic *** also analysed the relationship between various mechanisms and therapeutic resistance.

关键词： kras G12C drug resistance colorectal neoplasms combination therapy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Targeting small GTPases:emerging grasps on previously untamable *** by kras

引用

Signal Transduction and Targeted Therapy 2023年第6期8卷 2856-2894页

作者： Guowei Yin Jing Huang Johnny Petela Hongmei Jiang Yuetong Zhang Siqi Gong Jiaxin Wu Bei Liu Jianyou Shi Yijun Gao The Seventh Affiliated Hospital of Sun Yat-sen University Shenzhen518107China State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhou510060China Wake Forest University School of Medicine Winston-SalemNC27101USA School of Medicine Sun Yat-Sen UniversityShenzhen518107China National Biomedical Imaging Center School of Future TechnologyPeking UniversityBeijing100871China Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and TechnologyChengdu610072China

Small GTPases including Ras,Rho,Rab,Arf,and Ran are omnipresent molecular switches in regulating key cellular *** dysregulation is a therapeutic target for tumors,neurodegeneration,cardiomyopathies,and ***,small GTPases have been historically recognized as“undruggable”.Targeting kras,one of the most frequently mutated oncogenes,has only come into reality in the last decade due to the development of breakthrough strategies such as fragment-based screening,covalent ligands,macromolecule inhibitors,and *** kras^(G12C)covalent inhibitors have obtained accelerated approval for treating kras^(G12C)mutant lung cancer,and allele-specific hotspot mutations on G12D/S/R have been demonstrated as viable *** methods of targeting kras are quickly evolving,including transcription,immunogenic neoepitopes,and combinatory targeting with ***,the vast majority of small GTPases and hotspot mutations remain elusive,and clinical resistance to G12C inhibitors poses new *** this article,we summarize diversified biological functions,shared structural properties,and complex regulatory mechanisms of small GTPases and their relationships with human ***,we review the status of drug discovery for targeting small GTPases and the most recent strategic progress focused on targeting *** discovery of new regulatory mechanisms and development of targeting approaches will together promote drug discovery for small GTPases.

关键词： kras Targeting breakthrough

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

kras and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

引用

World Journal of Gastroenterology 2015年第5期21卷 1595-1605页

作者： Ju-Xiang Ye Yan Liu Yun Qin Hao-Hao Zhong Wei-Ning Yi Xue-Ying Shi Department of Pathology School of Basic Medical SciencesPeking University Third Hospital Peking University Health Science Center Department of Epidemiology and Biostatistics Peking University Health Science Center

AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic ***:Clinical and pathological information for 535 patients including 538 tumors was reviewed and *** analyses for exon 2 of kras gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was *** of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by *** of kras and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were *** between kras or BRAF mutations and MMR protein expression were also ***:The overall frequencies of kras and BRAF mutations were 37.9% and 4.4%,*** mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients kras mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PM

关键词： Colorectal carcinoma kras BRAF DNA mismatch repair

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Wild-Type kras and BRAF Could Predict Response to Cetuximab in Chinese Colorectal Cancer Patients

引用

Chinese Journal of Cancer Research 2011年第4期23卷 271-275页

作者： Jing Gao, Ting-ting Wang, Jing-wei Yu, Yan-yan Li, Lin Shen* Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing 100142 China.

Objective: To analyze the relationship between kras, BRAF mutations and the response to Cetuximab in Chinese colorectal cancer patients. Methods: A total of 273 Chinese colorectal cancer patients were evaluated for kras and BRAF mutations by Sanger sequencing. Among them, 59 patients with metastatic colorectal cancer (mCRC) were treated with Cetuximab in combination with chemotherapy from August 2005 to July 2009. Statistical analysis was conducted to assess the relationship between kras, BRAF mutations and the response or survival of 59 mCRC patients. Results: kras and BRAF mutation rates were 38.5% (105/273) and 5.1% (14/273), respectively, and kras/BRAF mutations were mutually exclusive. Among 59 patients treated with Cetuximab plus chemotherapy, kras and BRAF mutations were identified in 11 and 5 patients, respectively. The response rates and median progression-free survivals (PFS) in kras wild-type and mutant patients were 35.4% (17/48) vs. 9.1% (1/11) (P=0.054) and 153 days vs. 99 days (P=0.01), respectively. Also, the response rates and median PFS in BRAF wild-type and mutant patients were 37.2% (16/43) vs. 20% (1/5) (P=0.016) and 138 days vs. 90 days (P=0.036), respectively. Conclusion: Besides kras, assessing BRAF mutation should also be required to select patients eligible for Cetuximab. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.

关键词： kras BRAF Mutation Cetuximab Colorectal cancer

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Prognostic value of kras and BRAF mutations in curatively resected colorectal cancer

引用

World Journal of Gastroenterology 2015年第4期21卷 1275-1283页

作者： Shigenori Kadowaki Miho Kakuta Shuhei Takahashi Akemi Takahashi Yoshiko Arai Yoji Nishimura Toshimasa Yatsuoka Akira Ooki Kensei Yamaguchi Keitaro Matsuo Kei Muro Kiwamu Akagi Division of Gastroenterology Saitama Cancer CenterSaitama 362-0806Japan Department of Clinical Oncology Aichi Cancer Center HospitalAichi 464-8681Japan Division of Molecular Diagnosis and Cancer Prevention Saitama Cancer Center Saitama 362-0806Japan Division of Gastroenterological Surgery Saitama Cancer CenterSaitama 362-0806Japan Department of Preventive Medicine Kyushu University Faculty of Medical Sciences Fukuoka 812-8582Japan

AIM: To investigate the prognostic role of kras and BRAF mutations after adjustment for microsatellite instability(MSI) status in Japanese colorectal cancer(CRC) ***: We assessed kras and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage Ⅰ-Ⅲ CRC and examined associations of these mutations with disease-free survival(DFS) and overall survival(OS) using uni- and multivariate Cox proportional hazards ***: kras and BRAF mutations were detected in 312(38%) of 812 and 40(5%) of 811 tumors, respectively. kras mutations occurred more frequently in females than in males(P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender(P = 0.006), proximal tumor location(P kras mutations were associated with poorer DFS(HR = 1.35; 95%CI: 1.03-1.75) and OS(HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS(HR = 2.20; 95%CI: 1.19-4.06) and OS(HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the kras by MSI interaction test yielded statistically significant results for DFS and ***: kras and BRAF mutations are associated with inferior survival, independent of MSI status, inJapanese patients with curatively resected CRC.

关键词： Colorectal cancer kras BRAF Microsatellite instabi

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

From basic researches to new achievements in therapeutic strategies of kras-driven cancers

引用

Cancer Biology & Medicine 2019年第3期16卷 435-461页

作者： Mahsa Saliani Razieh Jalal Mohammad Reza Ahmadian Department of Chemistry Faculty of ScienceFerdowsi University of MashhadMashhad***Iran Department ofResearch Cell and Molecular Biology Institute of BiotechnologyFerdowsi University of MashhadMashhad***Iran Institute of Biochemistry and Molecular Biology II Medical FacultyHeinrich-Heine UniversityDüsseldorf40225Germany

Among the numerous oncogenes involved in human cancers, kras represents the most studied and best characterized cancerrelated *** therapeutic strategies targeting oncogenic kras(krasonc) signaling pathways have been suggested,including the inhibition of synthetic lethal interactions, direct inhibition of krasonc itself, blockade of downstream krasonc effectors, prevention of post-translational krasonc modifications, inhibition of the induced stem cell-like program, targeting of metabolic peculiarities, stimulation of the immune system, inhibition of inflammation, blockade of upstream signaling pathways,targeted RNA replacement, and oncogene-induced *** intensive and continuous efforts, krasonc remains an elusive target for cancer *** highlight the progress to date, this review covers a collection of studies on therapeutic strategies for kras published from 1995 to *** overview of the path of progress from earlier to more recent insights highlight novel opportunities for clinical development towards krasonc-signaling targeted therapeutics.

关键词： Direct inhibition downstream effectors oncogenic kras drug target sites small GTPases signal transduction targeting synthetic,lethal interactions therapeutic strategies

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

ARTICLE OPEN Mutant kras triggers functional reprogramming of tumor-associated macrophages in colorectal cancer

引用

Signal Transduction and Targeted Therapy 2021年第5期6卷 1498-1510页

作者： Huashan Liu Zhenxing Liang Chi Zhou Ziwei Zeng Fengwei Wang Tuo Hu Xiaowen He Xiaojian Wu Xianrui Wu Ping Lan Department of Coloreaal Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Clinical Innovation Department Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouChina Department of Colorectal Surgery Sun Yat-sen University Cancer CenterGuangzhouChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdongChina

Oncogenic kras has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of kras,where kras engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages(TAMs).In human CRC specimens,mutant kras positively correlates with the presence of *** activated kras in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and *** turn,kras-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab ***,kras drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-la(HIF-1a),a transcription factor that controls the expression of CSF2 and glycolytic *** kras increased the production of reactive oxygen species,an inhibitor of prolyl hydroxylase activity which decreases HIF-1a hydroxylation,leading to enhanced HIF-1a *** cell-extrinsic mechanism awards kras a critical role in engineering a permissive microenvironment to promote tumor malignancy,and may present new insights on potential therapeutic defense strategies against mutant kras tumors.

关键词： kras colorectal programming

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：