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Cancer Letters

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https://www.readbyqxmd.com/read/27913199/the-involvement-of-m2-macrophage-polarization-inhibition-in-fenretinide-mediated-chemopreventive-effects-on-colon-cancer
#1
Rong Dong, Yanling Gong, Wen Meng, Meng Yuan, Hong Zhu, Meidan Ying, Qiaojun He, Ji Cao, Bo Yang
Clinical studies have shown that fenretinide (4-HPR) is an attractive chemopreventive agent for cancer treatment. However, to date, few studies have demonstrated the mechanism of the preventive effect of 4-HPR. In our current study, we revealed that 4-HPR could significantly suppress IL-4/IL-13 induced M2-like polarization of macrophages, which was demonstrated by the reduced expression of M2 surface markers, the down-regulation of M2 marker genes, and the inhibition of M2-like macrophages promoted angiogenesis...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913198/argininosuccinate-synthetase-1-ass1-is-a-common-metabolic-marker-of-chemosensitivity-for-targeted-arginine-and-glutamine-starvation-therapy
#2
Yan Long, Wen-Bin Tsai, Dajuan Wang, David H Hawke, Niramol Savaraj, Lynn G Feun, Mien-Chie Hung, Helen H W Chen, Macus Tien Kuo
Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. ASS1 has been established as a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Here, we report that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913197/doxorubicin-induced-mitophagy-contributes-to-drug-resistance-in-cancer-stem-cells-from-hct8-human-colorectal-cancer-cells
#3
Chen Yan, Lan Luo, Chang-Ying Guo, Shinji Goto, Yoshishige Urata, Jiang-Hua Shao, Tao-Sheng Li
Cancer stem cells (CSCs) are known to be drug resistant. Mitophagy selectively degrades unnecessary or damaged mitochondria by autophagy during cellular stress. To investigate the potential role of mitophagy in drug resistance in CSCs, we purified CD133(+)/CD44(+) CSCs from HCT8 human colorectal cancer cells and then exposed to doxorubicin (DXR). Compared with parental cells, CSCs were more resistant to DXR treatment. Although DXR treatment enhanced autophagy levels in both cell types, the inhibition of autophagy by ATG7 silencing significantly increased the toxicity of DXR only in parental cells, not in CSCs...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27913196/nf-kb-regulated-exosomal-mir-155-promotes-the-inflammation-associated-with-arsenite-carcinogenesis
#4
Chao Chen, Fei Luo, Xinlu Liu, Lu Lu, Hui Xu, Qianlei Yang, Junchao Xue, Le Shi, Jun Li, Aihua Zhang, Qizhan Liu
In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells...
November 29, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894960/cancer-stem-cells-in-osteosarcoma
#5
Hannah K Brown, Marta Tellez-Gabriel, Dominique Heymann
Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and in some cases metastasis...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894959/inhibition-of-the-apelin-apelin-receptor-axis-decreases-cholangiocarcinoma-growth
#6
Chad Hall, Laurent Ehrlich, Julie Venter, April O'Brien, Tori White, Tianhao Zhou, Tien Dang, Fanyin Meng, Pietro Invernizzi, Francesca Bernuzzi, Gianfranco Alpini, Terry Lairmore, Shannon Glaser
PURPOSE: Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. METHODS: Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894958/poly-adp-ribose-polymerase-inhibitors-selectively-induce-cytotoxicity-in-tcf3-hlf-positive-leukemic-cells
#7
Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894957/dna-methylation-profiling-identifies-ptrf-cavin-1-as-a-novel-tumor-suppressor-in-ewing-sarcoma-when-co-expressed-with-caveolin-1
#8
Juan Huertas-Martínez, Franck Court, Santiago Rello-Varona, David Herrero-Martín, Olga Almacellas-Rabaiget, Miguel Sáinz-Jaspeado, Silvia Garcia-Monclús, Laura Lagares-Tena, Raquel Buj, Lourdes Hontecillas-Prieto, Ana Sastre, Daniel Azorin, Xavier Sanjuan, Roser López-Alemany, Sebastian Moran, Josep Roma, Soledad Gallego, Jaume Mora, Xavier García Del Muro, Paloma H Giangrande, Miquel A Peinado, Javier Alonso, Enrique de Alava, Dave Monk, Manel Esteller, Oscar M Tirado
Epigenetic modifications have been shown to be important in developmental tumors as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors, 7 cell lines, 10 healthy tissues and 4 human mesenchymal stem cells lines samples using the Infinium Human Methylation 450k. Differential methylation analysis between Ewing sarcoma and reference samples revealed 1,166 hypermethylated and 864 hypomethylated CpG sites (Bonferroni p<0.05, δ-β-value with absolute difference of >0.20) corresponding to 392 and 470 genes respectively...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894956/disulfiram-induces-anoikis-and-suppresses-lung-colonization-in-triple-negative-breast-cancer-via-calpain-activation
#9
Ji Young Kim, Nahyun Lee, Yoon-Jae Kim, Youngkwan Cho, Hyunsook An, Eunhye Oh, Tae-Min Cho, Daeil Sung, Jae Hong Seo
Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894955/blocking-preferential-glucose-uptake-sensitizes-liver-tumor-initiating-cells-to-glucose-restriction-and-sorafenib-treatment
#10
Hui-Lu Zhang, Ming-Da Wang, Xu Zhou, Chen-Jie Qin, Gong-Bo Fu, Liang Tang, Han Wu, Shuai Huang, Ling-Hao Zhao, Min Zeng, Jiao Liu, Dan Cao, Lin-Na Guo, Hong-Yang Wang, He-Xin Yan, Jie Liu
Cancer cells display altered metabolic phenotypes characterized by a high level of glycolysis, even under normoxic conditions. Because of a high rate of glycolytic flux and inadequate vascularization, tumor cells often suffer from nutrient deficiency and require metabolic adaptations to address such stresses. Although tumor-initiating cells (T-ICs) have been identified in various malignancies, the cells' metabolic phenotypes remain elusive. In this study, we observed that liver T-ICs preferentially survived under restricted glucose treatment...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27894954/dual-blocking-of-pi3k-and-mtor-signaling-by-nvp-bez235-inhibits-proliferation-in-cervical-carcinoma-cells-and-enhances-therapeutic-response
#11
Guifang Xie, Zhaoyong Wang, Yong Chen, Shuya Zhang, Lu Feng, Fanhui Meng, Zhiyun Yu
NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor that shows dramatic effects on many tumors, but its effects on cervical carcinoma cells are largely unknown. In the present study, we investigated the effects of NVP-BEZ235 on the proliferation and invasion of cervical carcinoma cells in vitro and clarified its mechanism of action. In cellular settings with human cervical carcinoma cell lines, this molecule effectively and specifically blocked dysfunctional PI3K/mTOR pathway activation, suppressed cell growth in a time- and concentration-dependent manner, led to G1 cell cycle arrest, and induced apoptosis...
November 25, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27887917/microrna-136-inhibits-cancer-stem-cell-activity-and-enhances-the-anti-tumor-effect-of-paclitaxel-against-chemoresistant-ovarian-cancer-cells-by-targeting-notch3
#12
Ju-Yeon Jeong, Hae-Youn Kang, Tae-Heon Kim, Gwang-Il Kim, Jin-Hyung Huh, Ah-Young Kwon, Se-Wha Kim, Sang-Geun Jung, Hee-Jung An
To identify microRNAs (miRNAs) regulating Notch3 expression in association with paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was significantly downregulated in OSC tissues relative to normal control tissues, and low expression of miR-136 correlated with poor overall in ovarian cancer patients. Artificial miR-136 overexpression significantly reduced cell viability, proliferation, CSC spheroid formation, and angiogenesis, and increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects of paclitaxel alone...
November 22, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#13
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27867016/vasohibin-2-promotes-epithelial-mesenchymal-transition-in-human-breast-cancer-via-activation-of-transforming-growth-factor-%C3%AE-1-and-hypoxia-dependent-repression-of-gata-binding-factor-3
#14
Min Tu, Zhanjun Li, Xian Liu, Nan Lv, Chunhua Xi, Zipeng Lu, Jishu Wei, Guoxin Song, Jianmin Chen, Feng Guo, Kuirong Jiang, Shui Wang, Wentao Gao, Yi Miao
Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27867015/cmtm3-decreases-egfr-expression-and-egf-mediated-tumorigenicity-by-promoting-rab5-activity-in-gastric-cancer
#15
Wanqiong Yuan, Baocai Liu, Xiaolin Wang, Ting Li, Hui Xue, Xiaoning Mo, Shuli Yang, Shigang Ding, Wenling Han
CMTM3 (CKLF-like MARVEL transmembrane domain containing 3), a tumor suppressor gene, is involved in multiple types of malignancies. CMTM3 knockdown promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Strong epidermal growth factor receptor1 (EGFR) expression is significantly associated with tumor metastasis and poor outcomes of gastric cancer patients. In this paper, we show that CMTM3 suppresses epidermal growth factor (EGF)-mediated migration and STAT3 signaling, downregulates EGFR expression via accelerating EGFR degradation in gastric cancer cells...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27865799/oleic-acid-induced-angptl4-enhances-head-and-neck-squamous-cell-carcinoma-anoikis-resistance-and-metastasis-via-up-regulation-of-fibronectin
#16
Chih-Jie Shen, Shih-Hung Chan, Chung-Ta Lee, Wan-Chen Huang, Jhih-Peng Tsai, Ben-Kuen Chen
Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion...
November 16, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27865798/adoptive-transfer-of-ex%C3%A2-vivo-expanded-v%C3%AE-9v%C3%AE-2-t-cells-in-combination-with-zoledronic-acid-inhibits-cancer-growth-and-limits-osteolysis-in-a-murine-model-of-osteolytic-breast-cancer
#17
Aneta Zysk, Mark O DeNichilo, Vasilios Panagopoulos, Irene Zinonos, Vasilios Liapis, Shelley Hay, Wendy Ingman, Vladimir Ponomarev, Gerald Atkins, David Findlay, Andrew Zannettino, Andreas Evdokiou
Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells...
November 16, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864115/synergistic-antitumor-activity-of-regorafenib-and-lapatinib-in-preclinical-models-of-human-colorectal-cancer
#18
Wen-Ji Zhang, Yong Li, Meng-Ning Wei, Yao Chen, Jian-Ge Qiu, Qi-Wei Jiang, Yang Yang, Di-Wei Zheng, Wu-Ming Qin, Jia-Rong Huang, Kun Wang, Wen-Juan Zhang, Yi-Jun Wang, Dong-Hua Yang, Zhe-Sheng Chen, Zhi Shi
Regorafenib significantly prolongs overall survival in patients with metastatic colorectal cancer (mCRC), but the overall clinical efficacy of regorafenib remains quite limited. Combination chemotherapy is a potentially promising approach to enhance anticancer activity, overcome drug resistance, and improve disease-free and overall survival. The current study investigates the antitumor activity of regorafenib in combination with lapatinib in preclinical models of human CRC. Our results show improved antitumor efficacy when regorafenib is combined with lapatinib both in vitro and in vivo...
November 15, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27864114/lipopolysaccharide-promotes-tumorigenicity-of-hepatic-progenitor-cells-by-promoting-proliferation-and-blocking-normal-differentiation
#19
Xiao-Yong Li, Xue Yang, Qiu-Dong Zhao, Zhi-Peng Han, Lei Liang, Xiao-Rong Pan, Jing-Ni Zhu, Rong Li, Meng-Chao Wu, Li-Xin Wei
Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate into mature hepatocytes or biliary epithelial cells (BECs). They are thought to be involved in repair of liver injury and the incidence of hepatic carcinoma. Their physiology is closely associated with the microenvironment where they reside. Lipopolysaccharide (LPS), an important component of the hepatic pathological microenvironment, is stored in the liver and affects many types of cells in various hepatosis. HPCs may also be influenced by LPS...
November 15, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27847303/sumoylation-of-large-tumor-suppressor-1-at-lys751-attenuates-its-kinase-activity-and-tumor-suppressor-functions
#20
Liu Mei, Lianwen Yuan, Wei Shi, Shihao Fan, Chao Tang, Xueying Fan, Wanlei Yang, Yu Qian, Musaddique Hussain, Ximei Wu
Large tumor suppressor (Lats) plays a critical role in maintaining cellular homeostasis and is the core to mediate Hippo growth-inhibitory signaling pathway. SUMOylation is a reversible and dynamic process that regulates a variety of cell functions. Here, we show that SUMOylation of Lats1 affects its kinase activity specifically towards Hippo signaling. Small ubiquitin-like modifier (SUMO) 1 interacts with and directly SUMOylates Lats1, whereas loss of SUMOylation pathway function disrupts Lats1 SUMOylation...
November 12, 2016: Cancer Letters
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