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https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#1
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430599/tak1-inhibitor-5z-7-oxozeaenol-sensitizes-cervical-cancer-to-doxorubicin-induced-apoptosis
#2
Shan Guan, Jiaxiong Lu, Yanling Zhao, Sarah E Woodfield, Huiyuan Zhang, Xin Xu, Yang Yu, Jing Zhao, Shayahati Bieerkehazhi, Haoqian Liang, Jianhua Yang, Fuchun Zhang, Surong Sun
Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress, is required for tumor cell viability and survival. Herein, we examined whether TAK1 inhibition is a potential therapeutic strategy for treating cervical cancer. We found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of Dox in a panel of cervical cancer cell lines...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429654/microrna-451-regulates-chemoresistance-in-renal-cell-carcinoma-by-targeting-atf-2-gene
#3
Xiang Sun, Longhua Lou, Kezhao Zhong, Lijuan Wan
Renal cell carcinoma (RCC) is a malignant tumor, which severely threatens human's life, moreover, the multi-drug resistance (MDR) under RCC undoubtedly strengthen the difficulties in the treatment. MiR-451 has been considered to play an important role in regulation of MDR in several cancers, but the role of it in MDR of RCC has not been explored. This study aims to explore the mechanism of miR-451 as a target to regulate chemotherapy resistance, which is crucial for further exploring novel therapy for RCC. Two human cell lines (ACHN and GRC-1) were performed in this study and adriamycin (ADM) was used to construct MDR cell lines...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428276/micellar-delivery-of-mir-34a-modulator-rubone-and-paclitaxel-in-resistant-prostate-cancer
#4
Di Wen, Yang Peng, Feng Lin, Rakesh K Singh, Ram I Mahato
Treatment of prostate cancer with paclitaxel (PTX) often fails due to development of chemoresistance caused by downregulation of the tumor suppressor gene miR-34a. In this study, we demonstrate that co-delivery of PTX and 2'-hydroxy-2,4,4',5,6'-pentamethoxychalcone (termed rubone) drives upregulation of miR-34a and chemosensitizes PTX-resistant prostate cancer cells, killing both cancer stem-like cells (CSCs) and bulk tumor cells. Rubone upregulated miR-34a and reversed its downstream target genes in DU145-TXR and PC3-TXR cells...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#5
Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427560/stress-adaptive-response-in-ovarian-cancer-drug-resistance-role-of-trap1-in-oxidative-metabolism-driven-inflammation
#6
Maria Rosaria Amoroso, Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Francesca Maddalena, Valentina Condelli, Matteo Landriscina, Franca Esposito
Metabolic reprogramming is one of the most frequent stress-adaptive response of cancer cells to survive environmental changes and meet increasing nutrient requirements during their growth. These modifications involve cellular bioenergetics and cross talk with surrounding microenvironment, in a dynamic network that connect different molecular processes, such as energy production, inflammatory response, and drug resistance. Even though the Warburg effect has long been considered the main metabolic feature of cancer cells, recent reports identify mitochondrial oxidative metabolism as a driving force for tumor growth in an increasing number of cellular contexts...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427212/high-myc-expression-and-transcription-activity-underlies-intra-tumoral-heterogeneity-in-triple-negative-breast-cancer
#7
Nidhi Gupta, Karen Jung, Chengsheng Wu, Abdulraheem Alshareef, Hind Alqahtani, Sambasivarao Damaraju, John R Mackey, Sunita Ghosh, Siham Sabri, Bassam S Abdulkarim, Gilbert Bigras, Raymond Lai
We have previously identified a novel intra-tumoral dichotomy in triple-negative breast cancer (TNBC) based on the differential responsiveness to a reporter containing the Sox2 regulatory region-2 (SRR2), with reporter responsive (RR) cells being more stem-like than reporter unresponsive (RU) cells. Using bioinformatics, we profiled the protein-DNA binding motifs of SRR2 and identified Myc as one of the potential transcription factors driving SRR2 activity. In support of its role, Myc was found to be highly expressed in RR cells as compared to RU cells...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#8
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28423714/usefulness-of-the-mrp2-promoter-to-overcome-the-chemoresistance-of-gastrointestinal-and-liver-tumors-by-enhancing-the-expression-of-the-drug-transporter-oatp1b1
#9
Elisa Herraez, Laura Sanchez-Vicente, Rocio I R Macias, Oscar Briz, Jose J G Marin
Tumor response to chemotherapy is often limited by drug export through ABC proteins. To overcome this problem, here we have investigated the usefulness of inducing the expression of the multidrug uptake transporter OATP1B1 under the control of the MRP2 promoter (MRP2pr). Human hepatoma cells (Alexander) were transfected with MRP2pr fragments of different length fused to the firefly luciferase ORF in order to select the shortest fragment with the highest response to dexamethasone, which was subsequently used to generate the chimeric construct MRP2pr-OATP1B1-V5...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423654/mcl-1-regulates-reactive-oxygen-species-via-nox4-during-chemotherapy-induced-senescence
#10
Abeba Demelash, Lukas W Pfannenstiel, Li Liu, Brian R Gastman
Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1's regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423543/mir-519d-impedes-cisplatin-resistance-in-breast-cancer-stem-cells-by-down-regulating-the-expression-of-mcl-1
#11
Qing Xie, Shuai Wang, Yue Zhao, Zhenchao Zhang, Chuan Qin, Xianjun Yang
Cancer stem cells are considered as the cell population which is responsible for chemoresistance and treatment failure in breast cancer patients. Therefore, it is urgent to explore the mechanism by which cancer stem cells survive under the treatment of chemotherapeutic drugs such as cisplatin. In this paper, we demonstrated significant decrease of miR-519d in breast cancer stem cells by quantitative RT-PCR analysis. Furthermore, we found the enforced expression of miR-519d in T-47D-cancer stem cells significantly increased their sensitivity to cisplatin through the apoptosis pathway...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423513/mir-503-5p-confers-drug-resistance-by-targeting-puma-in-colorectal-carcinoma
#12
Ke Xu, Guo Chen, Yanyan Qiu, Zeting Yuan, Hongchang Li, Xia Yuan, Jian Sun, Jianhua Xu, Xin Liang, Peihao Yin
The development of multidrug-resistance (MDR) is a major contributor to death in colorectal carcinoma (CRC). Here, we investigated the possible role of microRNA (miR)-503-5p in drug resistant CRC cells. Unbiased microRNA array screening revealed that miR-503-5p is up-regulated in two oxaliplatin (OXA)-resistant CRC cell lines. Overexpression of miR-503-5p conferred resistance to OXA-induced apoptosis and inhibition of tumor growth in vitro and in vivo through down-regulation of PUMA expression. miR-503-5p knockdown sensitized chemoresistant CRC cells to OXA...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423507/tgf-%C3%AE-independent-ctgf-induction-regulates-cell-adhesion-mediated-drug-resistance-by-increasing-collagen-i-in-hcc
#13
Yeonhwa Song, Jin-Sun Kim, Eun Kyung Choi, Joon Kim, Kang Mo Kim, Haeng Ran Seo
Hepatocellular carcinoma (HCC) is resistant to conventional chemotherapeutic agents and remains an unmet medical need. Here, we demonstrate a mechanism of cell adhesion-mediated drug resistance using a variety of HCC spheroid models to overcome environment-mediated drug resistance in HCC. We classified spheroids into two groups, tightly compacted and loosely compacted aggregates, based on investigation of dynamics of spheroid formation. Our results show that compactness of HCC spheroids correlated with fibroblast-like characteristics, collagen 1A1 (COL1A1) content, and capacity for chemoresistance...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423356/knockdown-of-mir-27a-sensitizes-colorectal-cancer-stem-cells-to-trail-by-promoting-the-formation-of-apaf-1-caspase-9-complex
#14
Rui Zhang, Jian Xu, Jian Zhao, Jinghui Bai
MicroRNAs have been proved to participate in multiple biological processes in cancers. For developing resistance to cytotoxic drug, cancer cells, especially the cancer stem cells, usually change their microRNA expression profile to survive in hostile environments. In the present study, we found that expression of microRNA-27a was increased in colorectal cancer stem cells. High level of microRNA-27a was indicated to induce the resistance to TNF-related apoptosis-inducing ligand (TRAIL). Knockdown of microRNA-27a resensitized colorectal cancer stem cells to TRAIL-induced cell death...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423353/silencing-prdm14-expression-by-an-innovative-rnai-therapy-inhibits-stemness-tumorigenicity-and-metastasis-of-breast-cancer
#15
Hiroaki Taniguchi, Daisuke Hoshino, Chiharu Moriya, Hitoshi Zembutsu, Nobuhiro Nishiyama, Hiroyuki Yamamoto, Kazunori Kataoka, Kohzoh Imai
PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers, it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic changes to cancer cells. Here, we examined the phenotypic characteristics and epigenetic and gene expression profiles of cancer cells that differentially express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy. PRDM14 expression was markedly increased in many different cancer types and correlated with poor survival of breast cancer patients...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419191/ppar%C3%AE-promotes-tumor-progression-via-activation-of-glut1-and-slc1-a5-transcription
#16
Wenbo Zhang, Ying Xu, QingGang Xu, Haifeng Shi, Juanjuan Shi, Yongzhong Hou
Malignant cancer cell uncontrolled growth depends on the persistent nutrient availability such as glucose and amino acids, which is required for cancer cell energetic and biosynthetic pathways. As a nuclear hormone receptor, peroxisome-proliferator-activated receptor δ (PPARδ) plays a critical role in inflammation and cancer, however, it is still unclear the regulatory mechanism of PPARδ on cancer cell metabolism. Here we found that PPARδ directly regulated neutral amino acid transporter SLC1-A5 (solutecarrier family 1 member 5) and glucose transporter-1(Glut1) gene transcription, leading to uptake of glucose and amino acid, activation of mTOR signaling, and tumor progression...
April 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28418119/endoplasmic-reticulum-stress-pathway-perk-eif2%C3%AE-confers-radioresistance-in-oropharyngeal-carcinoma-by-activating-nf-%C3%AE%C2%BAb
#17
Qiao Qiao, Chaonan Sun, Chuyang Han, Ning Han, Miao Zhang, Guang Li
Endoplasmic reticulum stress (ERS) plays an important role in the pathogenesis and development of malignant tumours, as well as in the regulation of radio- and chemoresistance in many malignancies. ERS signalling pathway protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2 (eIF2α) may induce aberrant activation of nuclear factor-κB (NF-κB). Our previous study showed that NF-κB confered radioresistance in lymphoma cells. However, whether PERK-eIF2α regulates radioresistance in oropharyngeal carcinoma through NF-κB activation is unknown...
April 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28418115/aggravation-of-diabetes-and-incompletely-deficient-insulin-secretion-in-a-case-with-type-1-diabetes-resistant-hla-drb1-15-02-treated-with-nivolumab
#18
Kimio Matsumura, Kaoru Nagasawa, Yoichi Oshima, Shouta Kikuno, Kyohei Hayashi, Akihiro Nishimura, Minoru Okubo, Hironori Uruga, Kazuma Kishi, Tetsuro Kobayashi, Yasumichi Mori
Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects especially in endocrine systems. Several cases of acute onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible HLA genotype for type 1 diabetes possibly suggesting that human leukocyte antigen (HLA) might be involved in the onset of diabetes with anti PD-1 therapy. We describe an atypical case of hyperglycemia after anti PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was administered nivolumab three times for chemoresistant adenocarcinoma of the lung...
April 18, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28416770/nid1-a-new-regulator-of-emt-required-for-metastasis-and-chemoresistance-of-ovarian-cancer-cells
#19
Ya Zhou, Yuanyuan Zhu, Xiaoyan Fan, Chundong Zhang, Yitao Wang, Lian Zhang, Huan Zhang, Tao Wen, Kaina Zhang, Xiao Huo, Xue Jiang, Youquan Bu, Ying Zhang
Nidogen-1 (NID1) has been identified as a novel candidate diagnostic biomarker of ovarian cancer in our previous study. Nevertheless, the role of NID1 in the pathogenesis of ovarian cancer is unclear. In the present study, we demonstrated that NID1 was a mesenchymal associated gene and its high expression was significantly correlated with shorter overall survival of ovarian cancer patients. The ectopic expression of NID1 in OVCAR-3 cells revealed a epithelial-mesenchymal transition (EMT) phenotype accompanied by enhancement of motility, invasiveness and cisplatin resistance, whereas the knockdown of NID1 was sufficient to convert HEY cells into epithelial phenotype with decreased capability of motility, invasiveness and cisplatin resistance...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416766/notch3-overexpression-enhances-progression-and-chemoresistance-of-urothelial-carcinoma
#20
Heng Zhang, Limei Liu, Chungang Liu, Jinhong Pan, Gensheng Lu, Zhansong Zhou, Zhiwen Chen, Cheng Qian
Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome...
March 13, 2017: Oncotarget
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