分类： 地球科学 >> 地质学 提交时间： 2021-12-01
摘要： Indochina developed continental-scale shear zones that record Cenozoic tectonic processes in SE Asia. Previous extrusion models that linked these shear zones with the northward indentation of the Indian continent, conflict with distributed conjugate strike-slip pairs and post-Oligocene rotation in Indochina. This paper presents evidence of coeval shearing along the Mogok-Shan Scarp fault in Myanmar, the western boundary of the Indochina block, previously proposed as a product of northward indentation of Indian Plate. The Kyanigan quarry along the northern Mogok-Shan Scarp fault exposes paragneiss, marble and quartzite schist. ‘σ’ structures, cored with garnet, in paragneiss record right-lateral shear sense, consistent with ‘σ’ and ’δ’ structures in L-tectonites in the Moulmein granitic mylonite to the south. U-Pb ages of metamorphic zircons of paragneiss and a biotite 39Ar-40Ar age of quartzite schist constrain deformation in the Kyanigan quarry to 33-21 Ma; a biotite 39Ar-40Ar age of mylonite at Moulmein is 26 Ma. These ages demonstrate Oligocene right-lateral shearing along the Mogok-Shan Scarp fault, coeval with other shear zones in Indochina. These Oligocene shear zones and strike-slip faults are conjugate structures recording left-lateral shear sense on NW-striking and right-lateral shear sense on N-S to NE-striking features. After restoration of ~80° clockwise rotation, the Oligocene conjugate strike-slip pairs in Indochina reflect approximate N-S-directed shortening, corresponding to northward subduction of the Indian ocean. This suggests that continental-scale intra-continental shearing may have been triggered by syn-subduction compression in SE Asia.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-15
Zhang, Bo
Wei, Peng
Hao, Junfeng
Zhao, Lijing
Zhang, Fenglin
Wei, Taotao
Wang, Jing
Huang, Zhen
Wei, Peng
Liu, Ying
Tu, Yaping
摘要： Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Cao, Wei
Zhang, Ran
Zhu, Xianbing
Mei, Lin
Chen, Hongbo
Zhang, Hongling
Huang, Laiqiang
Cao, Wei
Liu, Ying
Zhang, Ran
Wang, Teng
Zhu, Xianbing
Mei, Lin
Chen, Hongbo
Zhang, Hongling
Huang, Laiqiang
Cao, Wei
Liu, Ying
Zhang, Ran
Wang, Teng
摘要： Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia, on Gefitinib-resistant NSCLC cell lines in vitro and in vivo. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGF beta signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo. Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-11
摘要： Dasatinib-based therapy is often used as a second-line therapeutic strategy for imatinib-resistance gastrointestinal stromal tumors (GISTs); however, acquired aberrant activation of dasatinib target proteins, such as c-KIT and PDGFR13, attenuates the therapeutic efficiency of dasatinib. Combination therapy which inhibits the activation of dasatinib target proteins may enhance the cytotoxicity of dasatinib in GISTs. Bortezomib, a proteasome inhibitor, significantly inhibited cell viability and promoted apoptosis of dasatinib-treated GIST-TI cells, whereas GIST-TI cells showed little dasatinib cytotoxicity when treated with dasatinib alone, as the upregulation of c-KIT caused by dasatinib itself interfered with the inhibition of c-KIT and PDGFRI3 phosphorylation by dasatinib. Bortezomib induced internalization and degradation of c-KIT by binding c-KIT to Cbl, an E3 ubiquitin-protein ligase, and the subsequent release of Apaf-1, which was originally bound to the c-KIT-Hsp903-Apaf-1 complex, induced primary apoptosis in GISTTI cells. Combined treatment with bortezomib plus dasatinib caused cell cycle arrest in the G1 phase through inactivation of PDGFRP and promoted bortezomib-induced apoptosis in GIST-TI cells. Our data suggest that combination therapy exerts better efficiency for eradicating GIST cells and may be a promising strategy for the future treatment of GISTs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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