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Dexmedetomidine Promotes Angiogenesis and Vasculogenic mimicry in Human Hepatocellular Carcinoma through α^(2)-AR/HIF-1α/VEGFA Pathway

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Biomedical and Environmental Sciences 2022年第10期35卷 931-942页

作者： FANG Tao LIN Li YE Zhi Jian FANG Lian SHI Shuai YU Ke Da MIAO Hui Hui LI Tian Zuo Department of Anesthesiology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Department of Anesthesiology The Affiliated Jinhua Hospital of Wenzhou Medical UniversityJinhua 321000ZhejiangChina IVF centre The Affiliated Jinhua Hospital of Wenzhou Medical UniversityJinhua 321000ZhejiangChina

Objective Dexmedetomidine(DEX),the most specificα^(2)-adrenergic receptor agonist widely used for its sedative and analgesic properties,has been reported to upregulate HIF-1αexpression to protect hypoxic and ischemic ***,it is largely unclear whether DEX can also upregulate Hypoxiainducible factor-1 alpha(HIF-1α)expression and its downstream vascular endothelial growth factor-A(VEGFA)in cancer tissues with oxygen-deficient tumor *** We used SMMC-7721 cells,MHCC97-H cells,and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry(VM)and its *** normoxic(20%O^(2))and hypoxic(1%O^(2))conditions,DEX was used to intervene cells,and yohimbine was used to rescue *** The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range,and the addition of yohimbine inhibited this *** could activate HIF-1α/VEGFA pathway,which was further verified by silencing HIF-1α.Consistently,in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression,and enhance the number of VM channels and microvessel density(MVD).Conclusion We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma,whereasα^(2)-adrenergic receptor mediation might be the critical mechanisms.

关键词： Hepatocellular carcinoma Dexmedetomidine Yohimbine α^(2)-adrenergic receptor HIF-1a VEGFA vascular mimicry Angiogenesis

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ITGA5 predicts dual-drug resistance to Temozolomide and Avastin in glioma

ITGA5 predicts dual-drug resistance to Temozolomide and Avas...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Ying Shi Mengwan Wu yuyang Liu Chuan Xu University of Electronic Science and Technology of China 解放军总医院四川省肿瘤医院(四川省第二人民医院四川省癌症防治中心)

Aims: Anti angiotherapy(Avastin) is currently regarded as a promising option for glioma patients who are resistant to TMZ treatment. But ongoing clinical research failed to meet therapeutic expectations. This study aims to explore the pivotal genetic feature responsible for TMZ and Avastin resistance in glioma ***: We downloaded transcriptomic and methylation data of glioma patients from TCGA, CGGA and GEO databases, grouped these patients into resistant and non-resistant group based on their clinical profiles. Differentially expressed genes and pathways were identified and exhibited with software in R platform. Expression of candidate gene was compared in resistant and non-resistant glioma cells, while biological function of it was investigated by CCK8 assay, western blot and PAS ***: Change of cell morphology and polarity was closely associated with TMZ mono-resistance and TMZ/Avastin dual-resistance in glioma patients. Expression level of ITGA5 was effective in determining drug resistance and glioma patients’ outcome, which is regulated by methylation on two distinct sites. ITGA5 was augmented in TMZ-resistant glioma cells, while overexpressing ITGA5 altered cell promoted TMZ resistance ***: Both epigenetic and transcriptional levels of ITGA5 are effective in predicting TMZ and Avastin resistance, indicating that ITGA5 may serve as a predictor of treatment outcome in glioma patients.

关键词： glioma TMZ resistant Avastin resistant ITGA5 vascular mimicry

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Essence of resistance to anti-angiogenic therapy in tumors

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Chinese Medical Journal 2011年第24期124卷 4363-4363页

作者： CHEN Zhong-ping Sun Yat Sen Univ State Key Lab Oncol S China Ctr Canc Guangzhou 510060 Guangdong Peoples R China Sun Yat Sen Univ Dept Neurosurg Neurooncol Ctr Canc Guangzhou 510060 Guangdong Peoples R China

To the Editor： Recently, I read, with great interest, the article Patterns in the occurrence and development of tumors by Lin1 published in your honored journal. The author of the paper suggests that the mechanism of the occurrence and progress of tumors could involve the self-renewal of the cells and repair of injured tissue. The key players are the responding cells,

关键词： Tumor anti-angiogenic therapy vascular mimicry

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