Novel Combined Ato-C Treatment Synergistically Suppresses Proliferation of Bcr-Abl-Positive Leukemic Cells In Vitro and In Vivo
Chronic myelogenous leukemia (CML) accounts for 15-20% of all leukemias affecting adults. Despite recent advances in the development of specific Bcr-Abl tyrosine kinase inhibitors (TKIs), some CML patients suffer from relapse due to TKI resistance. Here, we assessed the efficacy of a novel combinatorial arsenic trioxide (ATO) and cisplatin (CDDP) treatment (Ato-C) in human Bcr-Abl-positive leukemic cells. Combination index analyses revealed that a synergistic interaction of ATO and CDDP elicits a wide range of effects in K562, KU-812, MEG-A2, and KCL-22 cells. (Source: Cancer Letters)
Source: Cancer Letters - June 23, 2018 Category: Cancer & Oncology Authors: Md Wahiduzzaman, Akinobu Ota, Sivasundaram Karnan, Ichiro Hanamura, Shohei Mizuno, Jo Kanasugi, Md Lutfur Rahman, Toshinori Hyodo, Hiroyuki Konishi, Shinobu Tsuzuki, Akiyoshi Takami, Yoshitaka Hosokawa Tags: Original Articles Source Type: research

HOTAIR is a REST-regulated lncRNA that promotes neuroendocrine differentiation in castration resistant prostate cancer
Long non-coding RNAs (lncRNAs) are emerging as novel diagnostic markers of prostate cancer (PCa) and new determinants of castration-resistant PCa (CRPC), an aggressive and metastatic form of PCa. In addition to androgen receptor (AR) signaling, neuroendocrine differentiation (NED) is associated with CRPC. Recent reports demonstrate that the downregulation of repressor element-1 silencing transcription factor (REST) protein is a key step in NED of PCa cells. Here, we report HOTAIR as a novel REST-repressed lncRNA that is upregulated in NED PCa cells and in CRPC. (Source: Cancer Letters)
Source: Cancer Letters - June 23, 2018 Category: Cancer & Oncology Authors: Yi-Ting Chang, Tzu-Ping Lin, Jui-Ting Tang, Mel Campbell, Yun-Li Luo, Shih-Yen Lu, Chia-Pei Yang, Ting-Yu Cheng, Ching-Hsin Chang, Tze-Tze Liu, Chi-Hung Lin, Hsing-Jein Kung, Chin-Chen Pan, Pei-Ching Chang Tags: Original Articles Source Type: research

Targeting the NRG1/HER3 pathway in tumor cells and cancer-associated fibroblasts with an anti-neuregulin 1 antibody inhibits tumor growth in pre-clinical models of pancreatic cancer
Neuregulin 1 (NRG1), a ligand for HER3 and HER4 receptors, is secreted by both pancreatic tumor cells (PC) and cancer-associated fibroblasts (CAFs), the latter representing the most abundant compound of pancreatic stroma. This desmoplastic stroma contributes to Pancreatic Ductal Adenocarcinoma (PDAC) aggressiveness and therapeutic failure by promoting tumor progression, invasion and resistance to chemotherapies. In the present work, we aimed at disrupting the complex crosstalk between PC and CAF in order to prevent tumor cell proliferation. (Source: Cancer Letters)
Source: Cancer Letters - June 20, 2018 Category: Cancer & Oncology Authors: Charline Ogier, Pierre-Emmanuel Colombo, Corinne Bousquet, Lucile Canterel-Thouennon, Pierre Sicard, V éronique Garambois, Gaëlle Thomas, Nadège Gaborit, Marta Jarlier, Nelly Pirot, Martine Pugnière, Nadia Vie, Céline Gongora, Pierre Martineau, Bruno Tags: Original Articles Source Type: research

Emerging roles of microRNAs in the metabolic control of immune cells
Immunometabolism is an emerging field that focuses on the role of cellular metabolism in the regulation of immune cells. Recent studies have revealed an intensive link between the metabolic state and the functions of immune cells. MicroRNAs (miRNAs) are small non-coding, single-stranded RNAs generally consisting of 18-25 nucleotides that exert crucial roles in regulating gene expression at the posttranscriptional level. Although the role of miRNAs in immune regulation has long been recognized, their roles in immunometabolism have not yet been well established. (Source: Cancer Letters)
Source: Cancer Letters - June 20, 2018 Category: Cancer & Oncology Authors: Qiuming Yao, Zhenyu Song, Bin Wang, Jin-an Zhang Tags: Mini-review Source Type: research

High collagen density augments mTOR-dependent cancer stem cells in ER α+ mammary carcinomas, and increases mTOR-independent lung metastases
We examined this interplay and response to mTOR inhibition using ERα+ adenocarcinomas from NRL-PRL females in combination with Col1a1tmJae/+ (mCol1a1) mice, which accumulate collagen-I around growing tumors. Orthotopic transplantation of tumor cells to mCol1a1 but not wildtype hosts resulted in striking desmoplasia. (Source: Cancer Letters)
Source: Cancer Letters - June 20, 2018 Category: Cancer & Oncology Authors: Michael P. Shea, Kathleen A. O'Leary, Kyle A. Wegner, Chad M. Vezina, Linda A. Schuler Tags: Original Articles Source Type: research

Pharmacologic inhibition of AKT leads to cell death in relapsed multiple myeloma
Multiple myeloma (MM) is a neoplastic plasma cell disorder with high disease recurrence rates. Novel therapeutic approaches capable of improving outcomes in patients with MM are urgently required. The AKT signalling plays a critical regulatory role in MM pathophysiology, including survival, proliferation, metabolism, and has emerged as a key therapeutic target. Here, we identified a novel AKT inhibitor, HS1793, and defined its mechanism of action and clinical significance in MM. HS1793 disrupted the interaction between AKT and heat shock protein 90, resulting in protein phosphatase 2A-modulated phosphorylated-AKT (p-AKT) r...
Source: Cancer Letters - June 19, 2018 Category: Cancer & Oncology Authors: In-Sung Song, Yu Jeong Jeong, Seung Hun Jeong, Hyoung Kyu Kim, Nam-Chul Ha, MyungGeun Shin, Kyung Soo Ko, Byoung Doo Rhee, Sungbo Shim, Sung-Wuk Jang, Jin Han Tags: Original Articles Source Type: research

Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines
Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. (Source: Cancer Letters)
Source: Cancer Letters - June 19, 2018 Category: Cancer & Oncology Authors: Maria Ferraiuolo, Claudio Pulito, Megan Finch-Edmondson, Etleva Korita, Anna Maidecchi, Sara Donzelli, Paola Muti, Massimo Serra, Marius Sudol, Sabrina Strano, Giovanni Blandino Tags: Original Articles Source Type: research

Corrigendum to “Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands” [Canc. Lett. 403 (2017) 98–107]
The authors regret to inform readers that the chemical structure presented in Fig. 1 is incorrect. The correct chemical structure for Ag8 is presented below. The authors would like to apologise for any inconvenience caused. (Source: Cancer Letters)
Source: Cancer Letters - June 19, 2018 Category: Cancer & Oncology Authors: Simon J. Allison, Maria Sadiq, Efstathia Baronou, Patricia A. Cooper, Chris Dunnill, Nikolaos T. Georgopoulos, Ayse Latif, Samantha Shepherd, Steve D. Shnyder, Ian J. Stratford, Richard T. Wheelhouse, Charlotte E. Willans, Roger M. Phillips Tags: Corrigendum Source Type: research

Oral recombinant methioninase (o-rMETase) is superior to injectable rMETase and overcomes acquired gemcitabine resistance in pancreatic cancer
Recombinant methioninase (rMETase) was administered as an injectable drug to target methionine dependence of cancer. Recently, we observed that rMETase could be administered orally (o-rMETase) in a patient-derived orthotopic xenograft (PDOX) mouse model of melanoma. Here, we determined the efficacy of o-rMETase on a pancreatic cancer PDOX model. Forty pancreatic cancer PDOX mouse models were randomized into four groups of 10 mice each. o-rMETase was significantly more effective than i.p.-rMETase, but combination of both was significantly more effective. (Source: Cancer Letters)
Source: Cancer Letters - June 18, 2018 Category: Cancer & Oncology Authors: Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Tasuku Kiyuna, Masuyo Miyake, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Michael Bouvet, Shree Ram Singh, Michiaki Unn Tags: Original Articles Source Type: research

CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer
Sulfasalazine has been repurposed to induce ferroptotic cancer cell death via inhibition of xc--cystine/glutamate antiporter (xCT). However, cancer cells are capable of developing mechanisms to evade cell death. Therefore, we sought to determine the molecular mechanisms underlying resistance to sulfasalazine-induced ferroptosis in head and neck cancer (HNC). The effects of sulfasalazine and pioglitazone were tested in various HNC cell lines. The effects of these drugs and inhibition and overexpression of CISD2 gene were determined by evaluating viability, cell death, lipid ROS production, mitochondrial iron, and mouse tumo...
Source: Cancer Letters - June 18, 2018 Category: Cancer & Oncology Authors: Eun Hye Kim, Daiha Shin, Jaewang Lee, Ah Ra Jung, Jong-Lyel Roh Tags: Original Articles Source Type: research

Rational design and development of a peptide inhibitor for the pd-1/pd-l1 interaction
We report here the rational design and validation of a peptide inhibitor to the PD-1/PD-L1 interaction as an attempt to develop a viable alternative to current inhibitory antibodies. We demonstrated, by biolayer interferometry and in silico docking simulations, that a PD-L1 peptide mimetic (PL120131) can interfere with the PD-1/PD-L1 interaction by binding to PD-1. We show that PL120131 is capable of inhibiting PD-1 mediated apoptotic signaling pathway and rescuing Jurkat cells and primary lymphocytes from apoptosis. (Source: Cancer Letters)
Source: Cancer Letters - June 16, 2018 Category: Cancer & Oncology Authors: Rebecca J. Boohaker, Vijaya Sambandam, Isaac Segura, James Miller, Mark Suto, Bo Xu Tags: Original Articles Source Type: research

Novel tumor necrosis factor- α induced protein eight (TNFAIP8/TIPE) family: Functions and downstream targets involved in cancer progression
The tumor necrosis factor (TNF)- α- induced protein 8 (TNFAIP8/TIPE) family is a death effector domain (DED)-containing protein family with four identified members: TNFAIP8 (TIPE), TNFAIP8L1 (TIPE1), TNFAIP8L2 (TIPE2), and TNFAIP8L3 (TIPE3). These proteins were found to play crucial roles in the regulation of immune homeostasis, i nflammation, and cancer development. Intensive research in the past two decades revealed a strong correlation of TIPE proteins with development of various cancers including cancers of the bladder, blood, bone, breast, cervix, colon, esophagus, endometrium, stomach, liver, lung, ovary, pancr...
Source: Cancer Letters - June 16, 2018 Category: Cancer & Oncology Authors: Ganesan Padmavathi, Kishore Banik, Javadi Monisha, Devivasha Bordoloi, Shabnam Bano, Frank Arfuso, Gautam Sethi, Fan Lu, Ajaikumar B. Kunnumakkara Tags: Mini-review Source Type: research

Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover
There is currently limited knowledge regarding the involvement of long non-coding RNAs (lncRNAs) in cancer development. We aimed to identify lncRNAs with important roles in pancreatic cancer progression. We screened for lncRNAs that were differentially expressed in pancreatic cancer tissues. Among 349 differentially expressed lncRNAs, Linc01060 showed the lowest expression in pancreatic cancer tissues compared with normal pancreatic tissues. Lower Linc01060 expression in pancreatic cancer tissues was significantly associated with a poor prognosis. (Source: Cancer Letters)
Source: Cancer Letters - June 15, 2018 Category: Cancer & Oncology Authors: Xiuhui Shi, Xingjun Guo, Xu Li, Min Wang, Renyi Qin Tags: Original Articles Source Type: research

ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells
The present study aimed to investigate the pathway related to MCL1 expression in ABT-263-treated human leukemia U937 cells. ABT-263 upregulated MCL1 protein expression but did not affect its mRNA level and protein stability. Notably, ABT-263 increased 4EBP1 mRNA decay and thus reduced 4EBP1 expression. Overexpression of 4EBP1 abrogated ABT-263-induced MCL1 upregulation. ABT-263-induced activation of IKK α/β-NFκB axis elicited autophagy of U937 cells, leading to reduced mRNA stability of 4EBP1. Inhibition of the IKKα/β-NFκB axis or autophagy mitigated the effect of ABT-263 on 4EBP1 and MCL1...
Source: Cancer Letters - June 15, 2018 Category: Cancer & Oncology Authors: Yuan-Chin Lee, Liang-Jun Wang, Chia-Hui Huang, Yi-Jun Shi, Long-Sen Chang Tags: Original Articles Source Type: research

Targeting Orai1-mediated store-operated calcium entry by RP4010 for anti-tumor activity in esophagus squamous cell carcinoma
Esophageal cancer (EC) is the 6  t h leading cause of cancer mortality worldwide with poor prognosis, hence more effective chemotherapeutic drugs for this deadly disease are urgently needed. We previously reported that high expression of Orai1, a store-operated Ca2+entry (SOCE) channel was associated with poor survival rate in EC patients and Orai1-mediated intracellular Ca2+ oscillations regulated cancer cell proliferation. Previous studies suggested that Orai1-mediated SOCE is a promising target for EC chemotherapy. (Source: Cancer Letters)
Source: Cancer Letters - June 14, 2018 Category: Cancer & Oncology Authors: Chaochu Cui, Yan Chang, Xiaoli Zhang, Sangyong Choi, Henry Tran, Kumar V. Penmetsa, Srikant Viswanadha, Liwu Fu, Zui Pan Tags: Original Articles Source Type: research

The TGF β-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling
Long non-coding RNAs (lncRNAs) play critical roles in multiple cellular processes in non-small cell lung cancer (NSCLC); however, the involvement of lncRNAs in the transforming growth factor-beta (TGF β) signaling pathway, the critical tumor cell epithelial-mesenchymal transition (EMT) and metastasis pathway, remains poorly understood. To address this issue, we compared the lncRNAs expression patterns of NSCLC cells treated with and without TGFβ1 treatment. We observed that one of the most prom inent hits, TGFβ-induced lncRNA (TBILA), promoted NSCLC progression and was upregulated in tumor tissues. (Source: Cancer Letters)
Source: Cancer Letters - June 13, 2018 Category: Cancer & Oncology Authors: Zhiliang Lu, Yuan Li, Yun Che, Jianbing Huang, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Ning Li, Nan Sun, Jie He Tags: Original Articles Source Type: research

Roles of microRNA in the immature immune system of neonates
Neonates have an immature immune system; therefore, their immune activities are different from the activities of adult immune systems. Such differences between neonates and adults are reflected by cell population constitutions, immune responses, cytokine production, and the expression of cellular/humoral molecules, which contribute to the specific neonatal microbial susceptibility and atopic properties. MicroRNAs (miRNAs) have been discovered to modulate many aspects of immune responses. Herein, we summarize the distinct manifestations of the neonatal immune system, including cellular and non-cellular components. (Source: Cancer Letters)
Source: Cancer Letters - June 13, 2018 Category: Cancer & Oncology Authors: Hong-Ren Yu, Lien-Hung Huang, Sung-Chou Li Tags: Mini-review Source Type: research

Nrf2-activated Expression of Sulfiredoxin Contributes to Urethane-induced 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. (Source: Cancer Letters)
Source: Cancer Letters - June 12, 2018 Category: Cancer & Oncology Authors: Murli Mishra, Hong Jiang, Hedy A. Chawsheen, Matthieu Gerard, Michel B. Toledano, Qiou Wei Tags: Original Articles Source Type: research

Deferoxamine suppresses esophageal squamous cell carcinoma cell growth via ERK1/2 mediated mitochondrial dysfunction
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. (Source: Cancer Letters)
Source: Cancer Letters - June 12, 2018 Category: Cancer & Oncology Authors: Linhua Lan, Wei Wei, Ying Zheng, Lili Niu, Xiaoling Chen, Dawei Huang, Yang Gao, Shouyong Mo, Jin Lu, Miaomiao Guo, Yongzhang Liu, Bin Lu Tags: Original Articles Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - June 10, 2018 Category: Cancer & Oncology Source Type: research

HDAC1-induced epigenetic silencing of ASPP2 promotes cell motility, tumour growth and drug resistance in renal cell carcinoma
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. (Source: Cancer Letters)
Source: Cancer Letters - June 8, 2018 Category: Cancer & Oncology Authors: Huayi Li, Xingwen Wang, Cheng Zhang, Yiwei Cheng, Miao Yu, Kunming Zhao, Wenjie Ge, Anyong Cai, Yao Zhang, Fengtong Han, Ying Hu Tags: Original Articles Source Type: research

The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma
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. (Source: Cancer Letters)
Source: Cancer Letters - June 8, 2018 Category: Cancer & Oncology Authors: Qi Shi, Luyan Shen, Bin Dong, Hao Fu, Xiaozheng Kang, Yongbo Yang, Liang Dai, Wanpu Yan, Hongchao Xiong, Zhen Liang, Keneng Chen Tags: Original Articles Source Type: research

Does metronomic chemotherapy induce tumor angiogenic dormancy? A review of available preclinical and clinical data
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. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Gianfranco Natale, Guido Bocci Tags: Mini-review Source Type: research

Cooperative multi-targeting of signaling networks by angiomiR-204 inhibits vasculogenic mimicry in breast cancer cells
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. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Yarely M. Salinas-Vera, Laurence A. Marchat, Ra úl 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 Tags: Original Articles Source Type: research

An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells
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 ...
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Danuta Jantas, Beata Grygier, S ławomir Gołda, Jakub Chwastek, Justyna Zatorska, Magdalena Tertil Tags: Original Articles Source Type: research

Human colorectal cancer initiation is bidirectional, and cell growth, metabolic genes and transporter genes are early drivers of tumorigenesis
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 adj acent to tumors (MT) in twenty-three sporadic CRC patients. In thirteen patients, the genetic distance (M-MT) between the B fractions is smaller than the distance b...
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Yi Hong, Soo Chin Liew, Lai Fun Thean, Choong Leong Tang, Peh Yean Cheah Tags: Original Articles Source Type: research

Methylation-mediated miR-155-FAM133A axis contributes to the attenuated invasion and migration of IDH mutant gliomas
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. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Guo-Hao Huang, Lei Du, Ningning Li, Ying Zhang, Yan Xiang, Jun-Hai Tang, Shuli Xia, Eric Erquan Zhang, Sheng-Qing Lv Tags: Original Articles Source Type: research

IGFBP2 promotes salivary adenoid cystic carcinoma metastasis by activating the NF- κB/ZEB1 signaling pathway
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. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Xiaofeng Yao, Yu Wang, Yuansheng Duan, Qiang Zhang, Ping Li, Rui Jin, Yingjie Tao, Wenchao Zhang, Xudong Wang, Chao Jing, Xuan Zhou Tags: Original Articles Source Type: research

Antitumor activity of nanoliposomes encapsulating the novobiocin analogue 6BrCaQ in a triple-negative breast cancer model in mice
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 ass...
Source: Cancer Letters - June 5, 2018 Category: Cancer & Oncology Authors: F élix 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 Tags: Original Articles Source Type: research

Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients
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. (Source: Cancer Letters)
Source: Cancer Letters - June 4, 2018 Category: Cancer & Oncology Authors: Elyse C. Page, Susan L. Heatley, David T. Yeung, Paul Q. Thomas, Deborah L. White Tags: Mini-review Source Type: research

Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma
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. (Source: Cancer Letters)
Source: Cancer Letters - June 4, 2018 Category: Cancer & Oncology Authors: Qing Zhang, Yinuo Li, Chunying Miao, Yuqiong Wang, Ying Xu, Ruifen Dong, Zhiwei Zhang, Brannan B. Griffin, Xingsheng Yang, Zhaojian Liu, Beihua Kong Tags: Original Articles Source Type: research

A CRISPR-Cas13a system for efficient and specific therapeutic targeting of mutant KRAS for pancreatic cancer treatment
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. Her e we demonstrate that the CRISPR-Cas13a system can be engineered for targeted therapy of mutant KRAS in pancreatic cancer. (Source: Cancer Letters)
Source: Cancer Letters - June 2, 2018 Category: Cancer & Oncology Authors: Xiao Zhao, Liang Liu, Jiayan Lang, Keman Cheng, Yongwei Wang, Xueyan Li, Jian Shi, Yanli Wang, Guangjun Nie Tags: Original Articles Source Type: research

RASSF6-mediated inhibition of Mcl-1 through JNK activation improves the anti-tumor effects of sorafenib in renal cell carcinoma
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. (Source: Cancer Letters)
Source: Cancer Letters - June 1, 2018 Category: Cancer & Oncology Authors: Ying-Ying Liang, Xu-Bin Deng, Li-Si Zeng, Xian-Tao Lin, Xun-Fan Shao, Bin Wang, Zhi-Wen Mo, Ya-Wei Yuan Tags: Original Articles Source Type: research

Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Source Type: research

Pyrazolo[1,5-a]pyrimidine TRPC6 Antagonists for the Treatment of Gastric Cancer
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. (Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Authors: 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 Tags: Original Articles Source Type: research

MicroRNA-mediated immune regulation in rheumatic diseases
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. (Source: Cancer Letters)
Source: Cancer Letters - May 31, 2018 Category: Cancer & Oncology Authors: Ian Kar Yin Lam, Jia Xin Chow, Chak Sing Lau, Vera Sau Fong Chan Tags: Mini-review Source Type: research

Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p
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. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Sudeepti S. Kuppa, Wei Jia, Shuying Liu, Ha Nguyen, Susan S. Smyth, Gordon B. Mills, Kevin K. Dobbin, William J. Hardman, Mandi M. Murph Tags: Original Articles Source Type: research

Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway
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. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Xiaogang Li, Hengyu Chen, Zhiqiang Liu, Zeng Ye, Shanmiao Gou, Chunyou Wang Tags: Original Articles Source Type: research

Targeting autophagy enhances apatinib-induced apoptosis via endoplasmic reticulum stress for human colorectal cancer
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. (Source: Cancer Letters)
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: 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 Tags: Original Articles Source Type: research

The hypoxic tumor microenvironment in vivo selects the tumor cells with increased survival against genotoxic stresses
Tumor sensitivity to radiation therapy has been known to be dependent on O2 concentrations. However, radiosensitivity of naturally occurring hypoxic tumor cells remains to be well fully investigated in direct comparison to that of their adjacent non-hypoxic tumor cells within the same tumor. We developed a hypoxia-sensing xenograft model using the hypoxia-response element (HRE)-driven enhanced green fluorescence protein (EGFP) as a hypoxia reporter to identify hypoxic tumor cells in situ. Here, we have found that naturally hypoxic tumor cells are moderately radioresistant compared to their neighboring non-hypoxic tumor cel...
Source: Cancer Letters - May 30, 2018 Category: Cancer & Oncology Authors: Hoon Kim, Qun Lin, Zhong Yun Tags: Original Articles Source Type: research

Piribedil disrupts the MLL1-WDR5 interaction and sensitizes MLL-rearranged acute myeloid leukemia (AML) to doxorubicin-induced apoptosis
Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA –approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non -MLL cells. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Xiong Zhang, Xingling Zheng, Hong Yang, Juan Yan, Xuhong Fu, Rongrui Wei, Xiaowei Xu, Zhuqing Zhang, Aisong Yu, Kaixin Zhou, Jian Ding, Meiyu Geng, Xun Huang Tags: Original Articles Source Type: research

Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model
Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and hu...
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Chulwon Kim, Seok-Geun Lee, Woong Mo Yang, Frank Arfuso, Jae-Young Um, Alan Prem Kumar, Jinsong Bian, Gautam Sethi, Kwang Seok Ahn Tags: Original Articles Source Type: research

Insight into the Roles of Vitamins C and D against Cancer: Myth or Truth?
The consumption of vitamins C and D for prevention and treatment of cancer is still an uncertain recommendation due to their controversial roles in cancer. The epidemiological studies document that vitamins C and D possess potential antineoplastic property. In addition, accumulating experimental studies strongly support their anticancer efficacy both in vitro and in vivo, although the mechanisms of action are not completely clear. Vitamin C at pharmacological concentration has cancer-selective cytotoxicity in several cancer cell lines. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Cai-Ning Zhao, Ya Li, Xiao Meng, Sha Li, Qing Liu, Guo-Yi Tang, Ren-You Gan, Hua-Bin Li Tags: Mini-review Source Type: research

New insights into the biological impacts of immune cell-derived exosomes within the tumor environment
Exosomes are a group of nano-sized membrane vesicles that transfer proteins, nucleic acids, and lipids to nearby and faraway cells, playing an important role in the intercellular communication within the extracellular environment. Emerging evidences show that exosomes derived from immunocytes, including dendritic cells, T cells, B cells, macrophages, natural killer cells and myeloid-derived suppressor cells, can play an intimate role in the crosstalk among immunocytes in a tumor microenvironment. (Source: Cancer Letters)
Source: Cancer Letters - May 29, 2018 Category: Cancer & Oncology Authors: Meng Shen, Xiubao Ren Tags: Mini-review Source Type: research

Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells
Melanoma, one of the toughest tumors to treat, features high metastasis and high lethality. Pinocembrin is a natural flavanone with versatile biological and pharmacological activities. Here, we evaluated the anti-tumor effects of pinocembrin against melanoma in vitro and in vivo. In vitro, pinocembrin inhibited the proliferation of melanoma cells (B16F10 and A375) in a dose-dependent manner. It induced endoplasmic reticulum stress via IRE1 α/Xbp1 pathway and triggered caspase-12/-4 mediated apoptosis in both cell lines. (Source: Cancer Letters)
Source: Cancer Letters - May 26, 2018 Category: Cancer & Oncology Authors: Yufei Zheng, Kai Wang, Yuqi Wu, Yifan Chen, Xi Chen, Chenyue W. Hu, Fuliang Hu Tags: Original Articles Source Type: research

Sulforaphane-N-Acetyl-Cysteine inhibited autophagy leading to apoptosis via Hsp70-mediated microtubule disruption
Sulforaphane-N-acetyl-cysteine (SFN-NAC) is a potential drug to inhibit human non-small cell lung cancer (NSCLC), but the underlying mechanisms are elusive. Here, we uncovered that SFN-NAC induced apoptosis via flow cytometer assay and transmission electron microscopy. Further, SFN-NAC increased LC3 II/LC3 I and the number of LC3 punctas, but Western blot showed that SFN-NAC inhibited cell autophagy in response to a co-treatment of Bafilomycin A1 and SFN-NAC. Furthermore, immunofluorescence staining and Western blot showed that SFN-NAC triggered microtubule disruption causing apoptosis via downregulating α-tubulin an...
Source: Cancer Letters - May 26, 2018 Category: Cancer & Oncology Authors: Yabin Hu, Yan Zhou, Gaoxiang Yang, Yalin Wang, Zhongnan Zheng, Juntao Li, Yuting Yan, Wei Wu Tags: Original Articles Source Type: research

Comprehensive pharmacogenomic profiling of human papillomavirus-positive and -negative squamous cell carcinoma identifies sensitivity to aurora kinase inhibition in KMT2D mutants
To address the unmet need for effective biomarker-driven targeted therapy for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and cervical cancer, we conducted a high-throughput drug screen using 1122 compounds in 13 HPV-positive and 11 matched HPV-negative cell lines. The most effective drug classes were inhibitors of polo-like kinase, proteasomes, histone deacetylase, and Aurora kinases. Treatment with a pan-Aurora inhibitor, danusertib, led to G2M arrest and apoptosis in vitro. (Source: Cancer Letters)
Source: Cancer Letters - May 25, 2018 Category: Cancer & Oncology Authors: Nene N. Kalu, Tuhina Mazumdar, Shaohua Peng, Pan Tong, Li Shen, Jing Wang, Upasana Banerjee, Jeffrey N. Myers, Curtis R. Pickering, David Brunell, Clifford C. Stephan, Faye M. Johnson Tags: Original Articles Source Type: research

Curcumin suppresses oncogenicity of human colon cancer cells by covalently modifying the cysteine 67 residue of SIRT1
SIRT1, an NAD+-dependent histone/protein deacetylase, has diverse physiological actions. Recent studies have demonstrated that SIRT1 is overexpressed in colorectal cancer, suggesting its oncogenic potential. However, the molecular mechanisms by which overexpressed SIRT1 induces the progression of colorectal cancer and its inhibition remain largely unknown. Curcumin (diferuloymethane), a major component of the spice turmeric derived from the plant Curcuma longa L., has been reported to exert chemopreventive and anti-carcinogenic effects on colon carcinogenesis. (Source: Cancer Letters)
Source: Cancer Letters - May 25, 2018 Category: Cancer & Oncology Authors: Yeon-Hwa Lee, Na-Young Song, Jinyoung Suh, Do-Hee Kim, Wonki Kim, Jihyae Ann, Jeewoo Lee, Jeong-Heum Baek, Hye-Kyung Na, Young-Joon Surh Tags: Original Articles Source Type: research

miRNAs in immune responses to Mycobacterium tuberculosis infection
Tuberculosis (TB) is one of the most fatal infectious diseases, affecting one third of the world's population. The causative agent, Mycobacterium tuberculosis (Mtb), has a well-established ability to circumvent the host's immune system for its long-term intracellular survival. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune response. They act by negatively regulating the expression levels of important genes in both innate and adaptive immunity. It has been established in recent studies that the host immune response against Mtb is regulated by many miRNAs, most of which are induced by Mtb infection....
Source: Cancer Letters - May 24, 2018 Category: Cancer & Oncology Authors: Tianshu Yang, Baoxue Ge Tags: Mini-review Source Type: research

Nemo-Like Kinase (NLK) Primes Colorectal Cancer Progression by Releasing the E2F1 Complex from HDAC1
Control of E2F1 activity is restricted via its interactions with RB1 and HDAC1. However, the detailed regulatory mechanisms underlying the E2F1/HDAC1 complex remain elusive. Here, we report that nemo-like kinase (NLK) boosts cell cycle progression, which facilitates tumor development by releasing the E2F1 protein from HDAC1. Deletion of NLK largely blocks colorectal tumor proliferation and development. Moreover, RNA-seq shows that cell cycle is arrested at the G1/S phase in NLK-deficient cells and that the expression of E2F complex-targeted genes is affected, whereas overexpression of NLK but not an NLK mutant restores the...
Source: Cancer Letters - May 24, 2018 Category: Cancer & Oncology Authors: Shang-Ze Li, Feng Zeng, Jun Li, Qi-Peng Shu, Hui-Hui Zhang, Jun Xu, Jian-Wei Ren, Xiao-Dong Zhang, Xue-Min Song, Run-Lei Du Tags: Original Articles Source Type: research