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Cancer Letters

Ana Lukic, Casper J E Wahlund, Cristina Gomez, Daniel Brodin, Bengt Samuelsson, Craig E Wheelock, Susanne Gabrielsson, Olof Radmark
Tumor-derived exosomes can modulate the cancer microenvironment and induce metastatic spread. Exosomes may carry enzymes for leukotriene (LT) biosynthesis, but the role of exosomal LTs has not been studied in cancer. We isolated exosomes and malignant cells from pleura exudates from 14 patients with non-small cell lung cancer. Lipidomic profiles, migration and apoptosis were determined. Both exosomes and primary cancer cells contained g-glutamyl transpeptidase 1 (GGT-1) and avidly transformed exogenous LTC4 to pro-tumorigenic LTD4 , for the cells to levels 100-fold above their endogenous CysLT production...
November 30, 2018: Cancer Letters
Shu-Sheng Wang, Yan Lv, Xin-Chun Xu, Yun Zuo, Yu Song, Ge-Ping Wu, Pei-Hua Lu, Zhi-Qing Zhang, Min-Bin Chen
Advanced stage nasopharyngeal carcinoma (NPC) has a poor prognosis. Triptonide ("TN") is a small molecule monomer extract from the ancient Chinese herb Tripterygium wilfordii Hook. We show that TN, at nanomolar concentrations, potently inhibited survival and proliferation of multiple established and primary human NPC cells. TN induced NPC cell cycle arrest and apoptosis activation. NPC cell migration and invasion were also inhibited by TN. Importantly, TN was non-cytotoxic to nasopharyngeal epithelial cells...
November 29, 2018: Cancer Letters
Hecun Zou, Hong-Hao Zhou
Single nucleotide polymorphisms (SNPs) are the most common genetic variants and universally present in human genome. GWASs have identified a great number of diseases or trait-associated SNPs, much of them are located on non-coding regions. Long intergenic non-coding RNAs (lincRNAs) are the major subtype of long non-coding RNAs, lincRNAs act crucial roles in various disorders and cellular models via multiple mechanisms. With the rapid growth of identified lincRNAs and SNPs, there are great demands for the investigation of SNPs in lincRNAs...
November 29, 2018: Cancer Letters
Hongye Zou, Mary B Sevigny, Shengquan Liu, David T Madden, Maggie C Louie
SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells...
November 29, 2018: Cancer Letters
Ruiqi Liu, Yuejin Li, Lantian Tian, Huawen Shi, Jiabei Wang, Yingjian Liang, Boshi Sun, Shuangjia Wang, Meng Zhou, Li Wu, Jianhua Nie, Binlin Lin, Shuli Tang, Yanqiao Zhang, Guangyu Wang, Chunhui Zhang, Jiguang Han, Benjie Xu, Lianxin Liu, Kunmei Gong, Tongsen Zheng
Gankyrin plays important roles in tumorigenicity and metastasis of hepatocellular carcinoma (HCC). We have for the first time investigated the effects of Gankyrin on glycolysis and glutaminolysis both in vitro and in vivo, including in patient-derived xenografts. We reported Gankyrin increases glucose consumption, lactate production, glutamine consumption and glutamate production in HCC through upregulating the expression of the transporters and enzymes involved in glycolysis and glutaminolysis, including HK2, GLUT1, LDHA, PKM2, ASCT2 and GLS1...
November 29, 2018: Cancer Letters
Jie Gu, Wei Mao, Wenjia Ren, Fengkai Xu, Qiaoliang Zhu, Chunlai Lu, Zongwu Lin, Zhilong Zhang, Yiwei Chu, Ronghua Liu, Di Ge
Cancer stem-like cells (CSCs) are regarded as sources of tumorigenesis, metastasis, and drug resistance, which limits current cancer therapies. Elucidating the molecular modes governing CSC properties is necessary to optimize therapeutic approaches. In this study, we discovered that ubiquitin-protein ligase E3C (UBE3C)-mediated ubiquitination is a key posttranslational mechanism involved in maintaining CSC properties of non-small-cell lung cancer (NSCLC). UBE3C was overexpressed in stem-like NSCLC cells and acted as a stemness enhancer...
November 29, 2018: Cancer Letters
Meng Jia, Yang Shi, Zhuyao Li, Jiaxiang Wang, Xiubo Lu
The microRNA-146-5p (miR-146b-5p) is known to be involved in the development of papillary thyroid cancer (PTC); however, the underlying mechanism is unclear. Here we have investigated the biological functions and underlying molecular mechanisms of miR-146b-5p in PTC. The expression of miR-146-5p was assessed in 92 pairs of PTC and adjacent normal tissues and showed correlation with the clinicopathological status such as the tumour size. Effects of miR-146b-5p and its direct target, coiled-coil domain containing 6 (CCDC6), on cell proliferation, migration, invasion, and cell cycle were evaluated through gain- and loss-of-function studies in vitro and in vivo...
November 29, 2018: Cancer Letters
Rangasudhagar Radhakrishnan, Ji Hee Ha, Muralidharan Jayaraman, Jinsong Liu, Katherine Moxley, Ciro Isidoro, Anil K Sood, Yong Sang Song, Danny N Dhanasekaran
Cancer Associated fibroblasts (CAFs) play a critical role in cancer progression, metastasis, and therapy resistance. Molecular events that confer CAF-phenotype to predecessor-cells are not fully understood. We demonstrate here that the ovarian cancer cell-conditioned medium (OCC-CM) induces CAF-phenotype in MRC5 lung-fibroblasts and it can be mimicked by LPA. While OCC-CM and LPA stimulated the expression of cellular CAF-markers by 3-days, they induced aerobic glycolysis, a metabolic marker for CAF, by 6 hrs...
November 29, 2018: Cancer Letters
Lei Zhang, Yan Chen, Li-Jun Zhang, Ming Wang, Dong-Lei Chang, Wei-Wei Wan, Bi-Xiang Zhang, Wan-Guang Zhang, Xiao-Ping Chen
Although hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC) cause a sever health problem worldwide, the underlying mechanisms are still elusive. This study aimed to investigate the responses of different cell types isolated from HBV transgenic mice. A cross-sectional set of hepatocytes and oval cells were obtained from HBV transgenic and control mice. Flow cytometry, immunohistochemistry and microarray were applied to investigate the cell biology of the hepatocytes and oval cells. Our results showed that HBV induced the proliferation of both cell oval cells and hepatocytes, and induced cell death of HBV hepatocytes while had minimal effects on oval cells...
November 29, 2018: Cancer Letters
Ji Young Hwang, Jung Hwa Park, Min Jae Kim, Woo Jean Kim, Ki-Tae Ha, Byung Tae Choi, Seo-Yeon Lee, Hwa Kyoung Shin
Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which remains incurable. Plant extracts are a potential source of potent anticancer medicines. In this study, we investigated the effect of isolinderalactone from Lindera aggregata on tumor growth using U-87 human glioblastoma cells. Treatment with isolinderalactone inhibited cell viability and promoted apoptotic cell death. In addition, intraperitoneal injection of isolinderalactone significantly inhibited tumor growth in a human GBM xenograft mouse model...
November 29, 2018: Cancer Letters
Min Xie, Tianshi Ma, Jiangyang Xue, Hongwei Ma, Ming Sun, Zhihong Zhang, Minjuan Liu, Yinghua Liu, Zhaoxia Wang, Wei De
Multiple studies have revealed that long non-coding RNAs (lncRNAs) extensively participate in human cancer malignant progression. The long intergenic non-protein coding RNA 707 (LINC00707), 3087 bp in length, was recently reported to be an essential oncogene in promoting lung adenocarcinoma cell proliferation and metastasis. However, its role in gastric cancer (GC) remains unclear. In this study, we identified that LINC00707 was excessively expressed in GC tissues and correlated with advanced stage, larger tumor size, lymph node metastasis and poorer prognosis in GC patients...
November 28, 2018: Cancer Letters
Varsha Thakur, Keman Zhang, Alyssa Savadelis, Patrick Zmina, Brittany Aguila, Scott M Welford, Fadi Abdul-Karim, Kristen W Bonk, Ruth A Keri, Barbara Bedogni
Breast cancer is the second leading cause of death among women in the US. Targeted therapies exist, however resistance is common and patients resort to chemotherapy. Chemotherapy is also a main treatment for triple negative breast cancer (TNBC) patients; while radiation is delivered to patients with advanced disease to counteract metastasis. Yet, resistance to both chemo- and radiotherapy is still frequent, highlighting a need to provide novel sensitizers. We discovered that MT1-MMP modulates DNA damage responses (DDR) in breast cancer...
November 28, 2018: Cancer Letters
Christina Brummer, Stephanie Faerber, Christina Bruss, Christian Blank, Ruben Lacroix, Sebastian Haferkamp, Wolfgang Herr, Marina Kreutz, Kathrin Renner
Tumors, including melanomas, frequently show an accelerated glucose metabolism. Mutations in the v-Raf murine sarcoma viral oncogene homolog B (BRAF) oncogene, detected in about 50 % of all melanomas, result in further enhancement of glycolysis. Therefore anti-metabolic substances might enhance the impact of RAF inhibitors. We have identified the two non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and lumiracoxib being able to restrict energy metabolism in human melanoma cells by targeting lactate release and oxidative phosphorylation (OXPHOS)...
November 24, 2018: Cancer Letters
Bowen Xie, Shuangyan Wang, Nian Jiang, Jian Jian Li
A mammalian cell houses two genomes located separately in the nucleus and mitochondria. During evolution, communications and adaptations between these two genomes occur extensively to achieve and sustain homeostasis for cellular functions and regeneration. Mitochondria provide the major cellular energy and contribute to gene regulation in the nucleus, whereas more than 98% of mitochondrial proteins are encoded by the nuclear genome. Such two-way signaling traffic presents an orchestrated dynamic between energy metabolism and consumption in cells...
November 24, 2018: Cancer Letters
Shaorong Deng, Qing Deng, Yingjie Zhang, Hao Ye, Xiaolan Yu, Yang Zhang, Grace Yq Han, Ping Luo, Mingyuan Wu, Yan Yu, Wei Han
CXCL4 is mainly produced by activated platelets, and certain somatic cells and cancer cells also express CXCL4. However, the physiological function of non-platelet-derived CXCL4 is unclear. Previously, we reported that CXCL4 produced by cancer cells accelerated tumor growth by suppressing the antitumor activities of cytotoxic T lymphocytes (CTLs). To elucidate the mechanism of CXCL4 in tumor immunity, we compared the CTLs and regulatory T cells (Tregs) from CXCL4-/- , CXCR3-/- and C57BL/6 mice overexpressing CXCL4 via intramuscular electroporation...
November 24, 2018: Cancer Letters
Yong Li, Xiaosong Li, Feifan Zhou, Austin Doughty, Ashley R Hoover, Robert E Nordquist, Wei R Chen
Phototherapy is a non-invasive or minimally invasive therapeutic strategy. Immunotherapy uses different immunological approaches, such as antibodies, vaccines, immunoadjuvants, and cytokines to stimulate the host immune system to fight against diseases. In cancer treatment, phototherapy not only destroys tumor cells, but also induces immunogenic tumor cell death to initiate a systemic anti-tumor immune response. When combined with immunotherapy, the effectiveness of phototherapy can be enhanced. Because of their special physical, chemical, and sometimes immunological properties, nanomaterials have also been used to enhance phototherapy...
November 23, 2018: Cancer Letters
Chenbo Ding, Wendong Tang, Hairu Wu, Xiaobo Fan, Junmin Luo, Jihong Feng, Kunming Wen, Guoqiu Wu
Pseudopodium enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, was recently implicated in cancer pathogenesis. However, its functional role in colorectal cancer (CRC) is not well known. Herein, we demonstrated that PEAK1 was frequently downregulated in CRC and significantly associated with tumor size, differentiation status, metastasis, and clinical stage. PEAK1 overexpression suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo, whereas knockout had the opposite effects...
November 22, 2018: Cancer Letters
Mian-Fu Cao, Lu Chen, Wei-Qi Dang, Xian-Chao Zhang, Xiang Zhang, Yu Shi, Xiao-Hong Yao, Qian Li, Jiang Zhu, Yong Lin, Sha Liu, Qian Chen, Yong-Hong Cui, Xia Zhang, Xiu-Wu Bian
Hybrid formation is a fundamental process in normal development and tissue homeostasis, while the presence and the biological role of hybrids between tumor-associated macrophages (TAMs) and glioblastoma (GBM) cells remain elusive. In this study, we observed that TAM-GBM cell hybrids existed in human GBM specimens as demonstrated by co-expression of glioma biomarkers (GFAP, IDH1R132H and PDGFRA) and macrophage biomarkers (CD68 and CD14). Furthermore, TAM-GBM cell hybrids could also be found in C57BL/6 mice orthotopically inoculated with mouse GBM cells labeled with RFP and after co-culture of bone marrow-derived macrophages from GFP-expressed mice with RFP-labeled GBM cells...
November 22, 2018: Cancer Letters
Honglin Cheng, Xin Li, Chuanlin Wang, Yujie Chen, Sijiang Li, Jincai Tan, Bing Tan, Yunfeng He
Tankyrase (TNKS) is a crucial mediator of Wnt signal transduction and has been recognized as a novel molecular target for Wnt-pathway dependent cancer. TNKS is stabilized by the ubiquitin-specific protease 25 (USP25). The effect of disruption of the interaction between TNKS and USP25 by small molecules on prostate cancer proliferation is unknown. In this study we conducted a hierarchical virtual screening with more than 200,000 compounds on the characterized structures of the USP25/TNKS-ARC5 protein complex...
November 22, 2018: Cancer Letters
Liam Friel Tremble, Morgan A O'Brien, Patrick F Forde
Electrochemotherapy is an emerging treatment modality for cancer patients which can effectively reduce tumour burden and induce immunogenic cell death. Electrochemotherapy is most commonly used with bleomycin as the drug of choice, here we examine the efficacy of electrochemotherapy with cisplatin. Electrochemotherapy with cisplatin was found to effectively reduce tumour growth in a range of murine models and induce significant intratumoural recruitment of myeloid and humoral immune cells. Following the observations of immune system mobilisation, we have shown an ability of electrochemotherapy to reduce metastatic potential as determined by tumour burden in the lung, and to exert an abscopal effect by reducing growth at distal untreated secondary tumours...
November 22, 2018: Cancer Letters
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