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Cancer Letters

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https://www.readbyqxmd.com/read/29906488/nrf2-activated-expression-of-sulfiredoxin-contributes-to-urethane-induced-lung-tumorigenesis
#1
Murli Mishra, Hong Jiang, Hedy A Chawsheen, Matthieu Gerard, Michel B Toledano, Qiou Wei
Lung cancer is the leading cause of cancer death worldwide. Cigarette smoking and exposure to chemical carcinogens are among the risk factors of lung tumorigenesis. In this study, we found that cigarette smoke condensate and urethane significantly stimulated the expression of sulfiredoxin (Srx) at the transcript and protein levels in cultured normal lung epithelial cells, and such stimulation was mediated through the activation of nuclear related factor 2 (Nrf2). To study the role of Srx in lung cancer development in vivo, mice with Srx wildtype, heterozygous or knockout genotype were subjected to the same protocol of urethane treatment to induce lung tumors...
June 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29906487/deferoxamine-suppresses-esophageal-squamous-cell-carcinoma-cell-growth-via-erk1-2-mediated-mitochondrial-dysfunction
#2
Linhua Lan, Wei Wei, Ying Zheng, Lili Niu, Xiaoling Chen, Dawei Huang, Yang Gao, Shouyong Mo, Jin Lu, Miaomiao Guo, Yongzhang Liu, Bin Lu
Deferoxamine (DFO) was found to modulate multiple cellular pathways involved in the growth of breast cancer, hepatocellular carcinoma, lung cancer and bladder cancer. However, the effect of DFO on esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we report that DFO-treated ESCC cells show strong anti-tumorigenic properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and promotion of apoptosis. Mechanistically, DFO significantly activated ERK1/2 signaling, which is reactive oxygen species (ROS)-dependent...
June 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29890208/the-identification-of-the-atr-inhibitor-ve-822-as-a-therapeutic-strategy-for-enhancing-cisplatin-chemosensitivity-in-esophageal-squamous-cell-carcinoma
#3
Qi Shi, Luyan Shen, Bin Dong, Hao Fu, Xiaozheng Kang, Yongbo Yang, Liang Dai, Wanpu Yan, Hongchao Xiong, Zhen Liang, Keneng Chen
Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. The endogenous DNA damage response confers chemoresistance to these agents by repairing DNA damage. The initiation and transduction of the DNA damage response (DDR) signaling pathway, which is dependent on the activation of ATM (ataxia-telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), is essential for DNA damage repair, the maintenance of genomic stability and cell survival...
June 8, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29890207/hdac1-induced-epigenetic-silencing-of-aspp2-promotes-cell-motility-tumour-growth-and-drug-resistance-in-renal-cell-carcinoma
#4
Huayi Li, Xingwen Wang, Cheng Zhang, Yiwei Cheng, Miao Yu, Kunming Zhao, Wenjie Ge, Anyong Cai, Yao Zhang, Fengtong Han, Ying Hu
Renal cell carcinoma (RCC) is highly resistant to chemotherapies. The lack of efficacious treatment for metastatic RCC has led to a poor 5-year survival rate. Here, we found that Apoptosis-stimulating protein of p53-2(ASPP2) was frequently decreased in primary RCC tissues in comparison with non-tumoural kidney controls. Decreased ASPP2 was correlated with high grades and poor outcomes of RCC. Further studies revealed that ASPP2 downregulation promoted EMT and increased resistance to 5-Fluorouracil (5-FU)-induced apoptosis...
June 8, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885520/igfbp2-promotes-salivary-adenoid-cystic-carcinoma-metastasis-by-activating-the-nf-%C3%AE%C2%BAb-zeb1-signaling-pathway
#5
Xiaofeng Yao, Yu Wang, Yuansheng Duan, Qiang Zhang, Ping Li, Rui Jin, Yingjie Tao, Wenchao Zhang, Xudong Wang, Chao Jing, Xuan Zhou
Metastasis is a major cause of poor prognosis in patients suffered with salivary adenoid cystic carcinoma (SACC), in which many factors are implicated. In this study, we identified that IGFBP2, overexpressed in SACC, correlated positively with perineural invasion or metastasis and indicated worse outcome. Moreover, IGFBP2 overexpression could dramatically improve motility and invasion capacity of SACC cells in vitro. Mechanically, IGFBP2 enhanced expression of ZEB1 in a NF-κB (p65)-dependent manner and then promoted epithelial-mesenchymal transition (EMT) in SACC...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885519/methylation-mediated-mir-155-fam133a-axis-contributes-to-the-attenuated-invasion-and-migration-of-idh-mutant-gliomas
#6
Guo-Hao Huang, Lei Du, Ningning Li, Ying Zhang, Yan Xiang, Jun-Hai Tang, Shuli Xia, Eric Erquan Zhang, Sheng-Qing Lv
Gliomas with isocitrate dehydrogenases genes mutation (IDHMT ) were found to be less aggressive than their wildtype (IDHWT ) counterparts. However, the mechanism remains unclear. The current study aims to investigate the role of silenced oncogenic microRNAs in IDHMT gliomas, which were largely ignored and may contribute to the less aggressive behavior of IDHMT gliomas. Microarrays, bioinformatics analysis of the data from TCGA and qPCR analysis of samples from our experimental cohort (LGG: IDHWT =10, IDHMT =31; GBM: IDHWT =34, IDHMT =9) were performed...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885518/an-endogenous-and-ectopic-expression-of-metabotropic-glutamate-receptor-8-mglur8-inhibits-proliferation-and-increases-chemosensitivity-of-human-neuroblastoma-and-glioma-cells
#7
Danuta Jantas, Beata Grygier, Sławomir Gołda, Jakub Chwastek, Justyna Zatorska, Magdalena Tertil
The present study aimed to determine the role of metabotropic glutamate receptor 8 (mGluR8) in tumor biology. Using various molecular approaches (RNAi or GRM8 cDNA), cell clones with downregulated (human neuroblastoma SH-SY5Y and human glioma LN229) or overexpressed (human glioma U87-MG and LN18 cell lines) mGluR8 were generated. Next, comparative studies on cell proliferation and migration rates, induction of apoptosis and chemosensitivity were performed among these clones. The mGluR8-downregulated SH-SY5Y clones proliferated faster and were more resistant to cytotoxic action of staurosporine, doxorubicin, irinotecan and cisplatin when compared to control cells...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885517/does-metronomic-chemotherapy-induce-tumor-angiogenic-dormancy-a-review-of-available-preclinical-and-clinical-data
#8
Gianfranco Natale, Guido Bocci
Tumor dormancy is the ability of cancer cells to survive in a non-proliferating state. This condition can depend on three main mechanisms: cell cycle arrest (quiescence or cell dormancy), immunosurveillance (immunologic dormancy), or lack of functional blood vessels (angiogenic dormancy). In particular, under angiogenic dormancy, cancer cell proliferation is counterbalanced by apoptosis owing to poor vascularization, impeding tumor mass expansion beyond a microscopic size, with an asymptomatic and non-metastatic state...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885516/cooperative-multi-targeting-of-signaling-networks-by-angiomir-204-inhibits-vasculogenic-mimicry-in-breast-cancer-cells
#9
Yarely M Salinas-Vera, Laurence A Marchat, Raúl García-Vázquez, Claudia Haydée González de la Rosa, Eduardo Castañeda-Saucedo, Napoleón Navarro Tito, Carlos Palma Flores, Carlos Pérez-Plasencia, José L Cruz-Colin, Ángeles Carlos-Reyes, José Sullivan López-González, María Elizbeth Álvarez-Sánchez, César López-Camarillo
RNA-based multi-target therapies focused in the blocking of signaling pathways represent an attractive approach in cancer. Here, we uncovered a miR-204 cooperative targeting of multiple signaling transducers involved in vasculogenic mimicry (VM). Our data showed that invasive triple negative MDA-MB-231 and Hs-578T breast cancer cells, but not poorly invasive MCF-7 cells, efficiently undergoes matrix-associated VM under hypoxia. Ectopic restoration of miR-204 in MDA-MB-231 cells leads to a potent inhibition of VM and reduction of number of branch points and patterned 3D channels...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29885515/human-colorectal-cancer-initiation-is-bidirectional-and-cell-growth-metabolic-genes-and-transporter-genes-are-early-drivers-of-tumorigenesis
#10
Yi Hong, Soo Chin Liew, Lai Fun Thean, Choong Leong Tang, Peh Yean Cheah
The role of stem cells in the development of solid tumors remains controversial. In colorectal cancers (CRC), this is complicated by the conflicting "top-down" or "bottom-up" hypotheses of cancer initiation. We profiled the expressions of genes from the top (T) and bottom (B) crypt fractions of normal-appearing human colonic mucosa (M) at least 20 cm away from the tumor as a baseline and compared this to the genes of matched mucosa adjacent to tumors (MT ) in twenty-three sporadic CRC patients...
June 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29883750/antitumor-activity-of-nanoliposomes-encapsulating-the-novobiocin-analogue-6brcaq-in-a-triple-negative-breast-cancer-model-in-mice
#11
Félix Sauvage, Elias Fattal, Walhan Al-Shaer, Stéphanie Denis, Emilie Brotin, Christophe Denoyelle, Cécile Blanc-Fournier, Balthazar Toussaint, Samir Messaoudi, Mouad Alami, Gillian Barratt, Juliette Vergnaud-Gauduchon
In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for the first time, the anti-proliferative effects of this drug in vivo in an orthotopic breast cancer model (MDA-MB-231 luc) using pegylated liposomes to allow its administration. Hsp90, hsp70 and hsp27 protein and mRNA expressions were not strongly affected after treatment meaning it did not induce a heat shock response often associated with resistance and poor prognosis...
June 5, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29879498/precision-medicine-approaches-may-be-the-future-for-crlf2-rearranged-down-syndrome-acute-lymphoblastic-leukaemia-patients
#12
Elyse C Page, Susan L Heatley, David T Yeung, Paul Q Thomas, Deborah L White
Breakthrough studies over the past decade have uncovered unique gene fusions implicated in acute lymphoblastic leukaemia (ALL). The critical gene, cytokine receptor-like factor 2 (CRLF2), is rearranged in 5-16% of B-ALL, comprising 50% of Philadelphia-like ALL and cooperates with genomic lesions in the Jak, Mapk and Ras signalling pathways. Children with Down Syndrome (DS) have a predisposition to developing CRLF2 rearranged-ALL which is observed in 60% of DS-ALL patients. These patients experience a poor survival outcome...
June 4, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29879497/anti-angiogenesis-effect-of-neferine-via-regulating-autophagy-and-polarization-of-tumor-associated-macrophages-in-high-grade-serous-ovarian-carcinoma
#13
Qing Zhang, Yinuo Li, Chunying Miao, Yuqiong Wang, Ying Xu, Ruifen Dong, Zhiwei Zhang, Brannan B Griffin, Xingsheng Yang, Zhaojian Liu, Beihua Kong
High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecologic malignancies. Currently, anti-angiogenesis therapy is the most promising strategy for the successful treatment of HGSOC. In this study, we found Neferine could inhibit the angiogenesis of ovarian cancer cells both in vitro and in vivo. Further analysis revealed that its suppressive effect on human umbilical vein endothelial cell (HUVEC) proliferation correlated with promoting cell cycle arrest and autophagy. The cell cycle genes were dose-dependently reduced and the level of LC3II/LC3I (microtubule associated protein 1 light chain 3) was increased...
June 4, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29870774/a-crispr-cas13a-system-for-efficient-and-specific-therapeutic-targeting-of-mutant-kras-for-pancreatic-cancer-treatment
#14
Xiao Zhao, Liang Liu, Jiayan Lang, Keman Cheng, Yongwei Wang, Xueyan Li, Jian Shi, Yanli Wang, Guangjun Nie
Mutant KRAS is a known driver oncogene in pancreatic cancer. However, this protein remains an "undruggable" therapeutic target. Inhibiting mutated KRAS expression at the mRNA level is a potentially effective strategy. Recently, a novel CRISPR-Cas effector, Cas13a has been reported to specifically knock down mRNA expression under the guidance of a single CRISPR-RNA in mammalian cells. Here we demonstrate that the CRISPR-Cas13a system can be engineered for targeted therapy of mutant KRAS in pancreatic cancer...
June 2, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29864454/rassf6-mediated-inhibition-of-mcl-1-through-jnk-activation-improves-the-anti-tumor-effects-of-sorafenib-in-renal-cell-carcinoma
#15
Ying-Ying Liang, Xu-Bin Deng, Li-Si Zeng, Xian-Tao Lin, Xun-Fan Shao, Bin Wang, Zhi-Wen Mo, Ya-Wei Yuan
Ras association domain family member 6 (RASSF6) has been shown to act as a tumor suppressor and predictor of poor prognosis in renal cell carcinoma (RCC). However, little is known about the effects of RASSF6 on sorafenib resistance or the underlying mechanism. Here, we show that RASSF6 expression positively correlates with sorafenib sensitivity in RCC cells and human samples. Stable ectopic overexpression of RASSF6 in RCC cell lines reduces resistance to sorafenib in vitro and in vivo. At a molecular level, RASSF6 activates the JNK signaling pathway, which further contributes to Mcl-1 inhibition...
June 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859876/microrna-mediated-immune-regulation-in-rheumatic-diseases
#16
Ian Kar Yin Lam, Jia Xin Chow, Chak Sing Lau, Vera Sau Fong Chan
MicroRNAs (miRNAs) are endogenous small, non-coding RNAs that regulate genome expression at the post-transcriptional level. They are involved in a wide range of physiological processes including the maintenance of immune homeostasis and normal function. Accumulating evidence from animal studies show that alterations in pan or specific miRNA expression would break immunological tolerance, leading to autoimmunity. Differential miRNA expressions have also been documented in patients of many autoimmune disorders...
May 31, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859875/pyrazolo-1-5-a-pyrimidine-trpc6-antagonists-for-the-treatment-of-gastric-cancer
#17
Mingmin Ding, Hongbo Wang, Chunrong Qu, Fuchun Xu, Yingmin Zhu, Guangyao Lv, Yungang Lu, Qingjun Zhou, Hui Zhou, Xiaodong Zeng, Jingwen Zhang, Chunhong Yan, Jiacheng Lin, Huai-Rong Luo, Zixing Deng, Yuling Xiao, Jinbin Tian, Michael X Zhu, Xuechuan Hong
Transient receptor potential canonical 6 (TRPC6) proteins form receptor-operated Ca2+ -permeable channels, which have been thought to bring benefit to the treatment of diseases, including cancer. However, selective antagonists for TRPC channels are rare and none of them has been tested against gastric cancer. Compound 14a and analogs were synthesized by chemical elaboration of previously reported TRPC3/6/7 agonist 4o. 14a had very weak agonist activity at TRPC6 expressed in HEK293 cells but exhibited strong inhibition on both 4o-mediated and receptor-operated activation of TRPC6 with an IC50 of about 1 μM...
May 31, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859300/targeting-autophagy-enhances-apatinib-induced-apoptosis-via-endoplasmic-reticulum-stress-for-human-colorectal-cancer
#18
Xi Cheng, Haoran Feng, Haoxuan Wu, Zhijian Jin, Xiaonan Shen, Jie Kuang, Zhen Huo, Xianze Chen, Haoji Gao, Feng Ye, Xiaopin Ji, Xiaoqian Jing, Yaqi Zhang, Tao Zhang, Weihua Qiu, Ren Zhao
Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma and some other solid tumors. However, the direct functional mechanisms of tumor lethality mediated by apatinib have not yet been fully characterized, and the precise mechanisms of drug resistance are largely unknown. Here, in this study, we demonstrated that apatinib could induce both apoptosis and autophagy in human colorectal cancer (CRC) via a mechanism that involved endoplasmic reticulum (ER) stress...
May 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859299/overexpression-of-mist1-reverses-the-epithelial-mesenchymal-transition-and-reduces-the-tumorigenicity-of-pancreatic-cancer-cells-via-the-snail-e-cadherin-pathway
#19
Xiaogang Li, Hengyu Chen, Zhiqiang Liu, Zeng Ye, Shanmiao Gou, Chunyou Wang
The role of transcription factors in cancer has attracted significant attention. Although genetic models indicate MIST1 functions as a tumor suppressor in mice, its role in human pancreatic cancer is unclear. We explored the expression and function of MIST1 in pancreatic cancer. Analysis of three GEO datasets (GSE16515, GSE15471, and GSE62165) showed MIST1 mRNA was significantly downregulated in human pancreatic cancer compared to normal pancreatic tissues. Moreover, MIST1 protein and mRNA expression were downregulated in pancreatic cancer cell lines compared to normal cells...
May 30, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29859298/autotaxin-exacerbates-tumor-progression-by-enhancing-mek1-and-overriding-the-function-of-mir-489-3p
#20
Sudeepti S Kuppa, Wei Jia, Shuying Liu, Ha Nguyen, Susan S Smyth, Gordon B Mills, Kevin K Dobbin, William J Hardman, Mandi M Murph
Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic 'AT-ATX' mice, whereby human wild-type autotaxin is expressed in liver under the control of the alpha-1 antitrypsin promoter, transgenic animals express augmented autotaxin in circulation and a percentage develop tumors...
May 30, 2018: Cancer Letters
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