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The impact of hypoxia in hepatocellular carcinoma metastasis

null

《医学前沿(英文)》 2014年 第8卷 第1期   页码 33-41 doi: 10.1007/s11684-013-0301-3

摘要:

Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondar y growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis.

关键词: hypoxia     hepatocellular carcinoma (HCC)     metastasis     hypoxia-inducible factor (HIF)    

Hypoxia-induced activity loss of a photo-responsive microtubule inhibitor azobenzene combretastatin A4

Yang An, Chao Chen, Jundong Zhu, Pankaj Dwivedi, Yanjun Zhao, Zheng Wang

《化学科学与工程前沿(英文)》 2020年 第14卷 第5期   页码 880-888 doi: 10.1007/s11705-019-1864-6

摘要: The conformation-dependent activity of azobenzene combretastatin A4 (Azo-CA4) provides a unique approach to reduce the side-effects of chemotherapy, due to the light-triggered conformation transition of its azobenzene moiety. Under hypoxic tumor microenvironment, however, the high expression of azoreductase can reduce azobenzene to aniline. It was postulated that the Azo-CA4 might be degraded under hypoxia, resulting in the decrease of its anti-tumor activity. The aim of this study was to verify such hypothesis in HeLa cells . The quantitative drug concentration analysis shows the ratiometric formation of degradation end-products, confirming the bioreduction of Azo-CA4. The tubulin staining study indicates that Azo-CA4 loses the potency of switching off microtubule dynamics under hypoxia. Furthermore, the cell cycle analysis shows that the ability of Azo-CA4 to induce mitotic arrest is lost at low oxygen content. Therefore, the cytotoxicity of Azo-CA4 is compromised under hypoxia. In contrast, combretastatin A4 as a positive control maintains the potency to inhibit tubulin polymerization and break down the nuclei irrespective of light irradiation and oxygen level. This work highlights the influence of hypoxic tumor microenvironment on the anti-tumor potency of Azo-CA4, which should be considered during the early stage of designing translational Azo-CA4 delivery systems.

关键词: hypoxia     microtubule inhibitor     drug delivery     azo-combretastatin A4     photo-responsive    

Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K

LI Yanhua, BI Zhigang

《医学前沿(英文)》 2007年 第1卷 第1期   页码 79-86 doi: 10.1007/s11684-007-0016-4

摘要: The aim of this research was to explore the effects and signaling pathway of ultraviolet-B (UVB) irradiation on the expression of hypoxia-inducible factor 1α (HIF-1α) and transferrin receptor (TfR). HIF-1α protein was measured by Western blot method. Expressions of epidermal growth factor receptor (EGFR), phosphor-EGF-R and TfR after UVB irradiation were determined with flow cytometry. After UVB irradiation, mRNA levels of HIF-1α and TfR were detected by real time-PCR. Results showed that compared with control groups, UVB was able to induce HIF1α and TfR protein expression in a dose- and time-dependent manner in HaCat cells (<0.05). TfR mRNA was expressed in a dose-dependent manner and reached a peak at the 8th hour in HaCat cells (<0.05) whereas HIF-1α mRNA expression was not affected by UVB treatment (>0.05). The EGFR/PI3K/AKT signaling pathway was required for the induction of HIF-1α and TfR expression induced by UVB. UVB induced activation of EGFR in HaCat cells and EGFR regulated expression of TfR and HIF-1α. EGFR (-/-) MEF did not increase the HIF1 expression following UVB irradiation (>0.05). In contrast, EGFR (+/+) MEF strongly enhanced HIF1α expression after UVB irradiation (<0.05). PD153035, a selective inhibitor of EGFR tyrosine kinase, inhibited the TfR protein expression in UVB-treated cells in a dose-dependent manner (P<0.05). PI3K inhibitors, LY294002 and wortmannin, inhibited HIF-1? and TfR expressions induced by UVB (P<0.05). The DEC1 (-/-) Ha-Cat cells did not increase their TfR and HIF-1α expressions following UVB irradiation (>0.05). In contrast, DEC1 (+/+) HaCat cells strongly enhanced TfR and HIF-1? protein expression after UVB irradiation (P<0.05). We conclude that UVB induces TfR and HIF-1αexpressions via EGFR/PI3K/AKT/DEC1 signaling pathway.

Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of

Bin YANG MS , Xianglin YUAN , Yanmei ZOU , Qingsong XI , Guoxian LONG , Qiang FU , Guangyuan HU MM ,

《医学前沿(英文)》 2009年 第3卷 第3期   页码 303-308 doi: 10.1007/s11684-009-0060-3

摘要: The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α (HIF-1α) were investigated. The Hela cells were divided into three groups, namely, H (non-transfected Hela cells), H (pGenesil-1 empty plasmid-transfected Hela cells), and H (HIF-1α-shRNA plasmid-transfected Hela cells), and were cultured under hypoxia (1% O) and normoxia for 48h. The expression of HIF-1α, E-cadherin, β-catenin, and actin was detected using Western blot. The scratch test and the invasion assay were applied to examine the invasion in each group. The expression of HIF-1α, E-cadherin, and β-catenin in tumor grafts was assayed immunohistochemically. Western blot results revealed that the bands of HIF-1α, E-cadherin, β-catenin, and actin proteins were detected in the H and H groups under hypoxia for 48h. The expression of E-cadherin, β-catenin, and actin was detected in the H group under hypoxia for 48h, and normoxia. In the H, H, and H groups under normoxia, and the H group under hypoxia for 48h, no expression of HIF-1α was detectable. The scratch test showed that the invasive ability in the H group was significantly alleviated. Immunohistochemically, it was found that there was a significant difference in the expression of HIF-1α, E-cadherin, and β-catenin between the H and H groups (<0.05), but the difference was not significant between the H and H groups. It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins (E-cadherin, β-catenin, and actin) depend on HIF-1α.

关键词: hypoxia     actin     β     -catenin     E-cadherin     invasion    

Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured

YANG Yingzhong, MA Lan, GE Rili, FAN Wenhong, ZHU Lingling, ZHAO Tong, WU Yan, FAN Ming

《医学前沿(英文)》 2008年 第2卷 第3期   页码 239-243 doi: 10.1007/s11684-008-0045-7

摘要: Internal standards are critical for quantitative RNA analyses. Housekeeping genes are often used as internal standards with the assumption that their expression levels remain relatively constant in different experimental conditions. In this study, four commonly used housekeeping genes, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ?-actin, 28S rRNA and 18S rRNA were selected to test whether this assumption is tenable under hypoxic conditions. We tested the RNA expression level of these four genes in different hypoxic conditions. Rats subjected to acute hypoxia for 2 hours were used for tissue detection. Primary cultured neural stem cells from E13 fetal rats were treated with 3% O or 10% O for 24 hours for experiments. In both experiments, expression levels of 28S rRNA and 18S rRNA were constant, independent of hypoxia types. However, expression levels of GAPDH and ?-actin were all changed in all kinds of hypoxic conditions. In particular, the mRNA expression level of GAPDH was increased by 43.4% under 3% O hypoxic conditions. These results suggest that 18S rRNA and 28S rRNA are reliable internal controls for comparative analyses of transcription under hypoxia. GAPDH appears particularly unfavorable for this purpose in hypoxic conditions.

关键词: Glyceraldehyde-3-phosphate dehydrogenase     comparative     constant     unfavorable     independent    

Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor

Yao Yao, Rui Zhou, Rui Bai, Jing Wang, Mengjiao Tu, Jingjing Shi, Xiao He, Jinyun Zhou, Liu Feng, Yuanxue Gao, Fahuan Song, Feng Lan, Xingguo Liu, Mei Tian, Hong Zhang

《医学前沿(英文)》 2021年 第15卷 第3期   页码 472-485 doi: 10.1007/s11684-021-0832-y

摘要: Hypoxia conditioning could increase the survival of transplanted neuronal progenitor cells (NPCs) in rats with cerebral ischemia but could also hinder neuronal differentiation partly by suppressing mitochondrial metabolism. In this work, the mitochondrial metabolism of hypoxia-conditioned NPCs (hcNPCs) was upregulated via the additional administration of resveratrol, an herbal compound, to resolve the limitation of hypoxia conditioning on neuronal differentiation. Resveratrol was first applied during the neuronal differentiation of hcNPCs and concurrently promoted the differentiation, synaptogenesis, and functional development of neurons derived from hcNPCs and restored the mitochondrial metabolism. Furthermore, this herbal compound was used as an adjuvant during hcNPC transplantation in a photothrombotic stroke rat model. Resveratrol promoted neuronal differentiation and increased the long-term survival of transplanted hcNPCs. 18-fluorine fluorodeoxyglucose positron emission tomography and rotarod test showed that resveratrol and hcNPC transplantation synergistically improved the neurological and metabolic recovery of stroke rats. In conclusion, resveratrol promoted the neuronal differentiation and therapeutic efficiency of hcNPCs in stroke rats via restoring mitochondrial metabolism. This work suggested a novel approach to promote the clinical translation of NPC transplantation therapy.

关键词: neuronal progenitor cells     resveratrol     cerebral ischemia     neuronal differentiation     mitochondrial metabolism     positron emission tomography    

Potential functions of esophageal cancer-related gene-4 in the cardiovascular system

Rui Zhou, Yuanshu Liu, Wenjun Huang, Xitong Dang

《医学前沿(英文)》 2019年 第13卷 第6期   页码 639-645 doi: 10.1007/s11684-019-0701-0

摘要: Esophageal cancer-related gene-4 ( ) is cloned from the normal epithelium of the esophagus. It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis, and expression levels are inversely correlated with the malignant phenotype of tumor cells, validating that is a real tumor suppressor gene. Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins, encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells, specialized epithelial cells, and human leukocytes, where it can be processed tissue dependently into several small peptides upon cell activation. Ecrg4 is expressed in a wide variety of other cells/tissues, including cardiomyocytes and conduction system of the heart,, the glomus cells of the carotid body, adrenal glands, choroid plexus, and leukocytes among others, where it exerts distinct functions, such as promoting/suppressing inflammation, inducing neuron senescence, stimulating the hypothalamus–pituitary–adrenal axis, maintaining the stemness of stem cells, participating in the rhythm and rate control of the heart, and possibly gauging the responsiveness of the cardiovascular system (CVS) to hypoxia, in addition to tumor suppression. Here, we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.

关键词: tumor suppressor gene     esophageal cancer-related gene-4     cardiovascular disease     hypoxia    

功能影像检测食管癌放疗过程中再增殖和乏氧以及预测临床疗效研究

于金明

《中国工程科学》 2012年 第14卷 第7期   页码 9-19

摘要:

18F-FLT PET能监测食管鳞癌放疗过程中肿瘤和正常组织的生物学变化,其较18F-FDG PET能较好区分炎症和肿瘤,能检测食管肿瘤放疗过程中的加速再增殖,18F-FETNIM PET能检测食管鳞癌的乏氧状态,18F-FLT PET和18F-FETNIM PET作为一种非创伤性的影像学技术,能为肿瘤医生提供一个早期评价治疗反应,检测放疗过程中的再增殖克隆源细胞、乏氧和评价新辅助治疗疗效的手段。18F-FLT PET和18F-FETNIM PET能为放射治疗确定“再增殖”和“乏氧”生物学靶区,以通过剂量调强放疗提高再增殖和乏氧区域放疗剂量,提高肿瘤的局部控制率和远期生存。

关键词: 食管肿瘤     放射疗法     正电子发射型     再增殖     乏氧    

标题 作者 时间 类型 操作

The impact of hypoxia in hepatocellular carcinoma metastasis

null

期刊论文

Hypoxia-induced activity loss of a photo-responsive microtubule inhibitor azobenzene combretastatin A4

Yang An, Chao Chen, Jundong Zhu, Pankaj Dwivedi, Yanjun Zhao, Zheng Wang

期刊论文

Ultraviolet-B induced expression of hypoxia-inducible factor 1α, transferrin receptor through EGFR/PI3K

LI Yanhua, BI Zhigang

期刊论文

Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of

Bin YANG MS , Xianglin YUAN , Yanmei ZOU , Qingsong XI , Guoxian LONG , Qiang FU , Guangyuan HU MM ,

期刊论文

Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured

YANG Yingzhong, MA Lan, GE Rili, FAN Wenhong, ZHU Lingling, ZHAO Tong, WU Yan, FAN Ming

期刊论文

Resveratrol promotes the survival and neuronal differentiation of hypoxia-conditioned neuronal progenitor

Yao Yao, Rui Zhou, Rui Bai, Jing Wang, Mengjiao Tu, Jingjing Shi, Xiao He, Jinyun Zhou, Liu Feng, Yuanxue Gao, Fahuan Song, Feng Lan, Xingguo Liu, Mei Tian, Hong Zhang

期刊论文

Potential functions of esophageal cancer-related gene-4 in the cardiovascular system

Rui Zhou, Yuanshu Liu, Wenjun Huang, Xitong Dang

期刊论文

功能影像检测食管癌放疗过程中再增殖和乏氧以及预测临床疗效研究

于金明

期刊论文