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Cancer Biology & Therapy

Zhongqiu Wang, Binhui Ren, Jianfeng Huang, Rong Yin, Feng Jiang, Qin Zhang
Esophageal Squamous Cell Carcinoma (ESCC) belongs to malignant tumor of human digestive system. It has greatly threatened human health both mentally and physically. Long non-coding RNAs have been discovered to be special molecular regulators in various cancers, including ESCC. LncRNA DUXAP10 is a newfound RNA, which is able to improve the progression of cancers 1-3 . In this study, DUXAP10 was certified to be upregulated in ESCC tissues and cells. Besides, it was positively correlated with short survival time...
September 14, 2018: Cancer Biology & Therapy
Fukun Chen, Zhiping Feng, Jialun Zhu, Pengjie Liu, Chuanzhou Yang, Rongkai Huang, Zhiyong Deng
OBJECTIVE: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. METHODS: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis...
September 12, 2018: Cancer Biology & Therapy
Hairong Huang, Lei Wei, Tao Qin, Nan Yang, Zhongdong Li, Zhiyun Xu
Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly cancers worldwide, especially in Eastern Asia. It has been indicated that circular RNAs (circRNA) are the key regulators in the development and progression of human cancers. We therefore evaluated the expression and regulation effects of ciRS-7 on the progression of ESCC, which is a recently identified circRNA and acts as a natural competing endogenous RNA. The expression of ciRS-7 was significantly increased in the ESCC tissues and cells as compared with their corresponding controls...
September 12, 2018: Cancer Biology & Therapy
Muhui Lin, Zhicheng Yao, Na Zhao, Chaodong Zhang
Glioblastoma are among the most common forms of cancer affecting the central nervous system, and yet there is currently no effective means of treating them. In the current study, we reported that tousled-like kinase 2 (TLK2) is a key factor in glioblastoma that modulates SRC signaling, thereby driving tumor malignancy. TLK2 is commonly upregulated in glioblastoma, and such upregulation was associated with poor patient outcomes. TLK2 overexpression induced cell growth, migration, invasion, and epithelial-mesenchymal transition, and cell cycle arrest, while TLK2 knockdown had the opposite effect...
September 12, 2018: Cancer Biology & Therapy
Chi Ma, Manoj Nepal, Jin-Hee Kim, Ping Fan, Peiwen Fei
In the past 25 years, incidence rates of breast cancer have risen about 30% in westernized countries. Mutations in BRCA1 and BRCA2 are the most prominent cause of breast cancer. However, these cancer susceptibility genes (BRCAs) only account for a few percent of women suffering breast tumor. With our understanding that BRCAs are Fanconi Anemia (FA) genes, investigations into the FA signaling network should provide a previously unrecognized key to unlock in-depth insights into both etiology and treatment of breast cancer...
September 6, 2018: Cancer Biology & Therapy
Laurence Booth, Jane L Roberts, Rumeesa Rais, Richard E Cutler, Irmina Diala, Alshad S Lalani, Andrew Poklepovic, Paul Dent
Cancers expressing mutant RAS are associated with a weaker response to chemotherapy and a shorter overall patient survival. We have demonstrated that the irreversible inhibitor of ERBB1/2/4, neratinib, inhibits ERBB1/2/4 and causes their internalization and autolysosomal degradation. Fellow-traveler membrane proteins with RTKs, including mutant K-/N-RAS, were also degraded. We discovered that the CDK4/6 inhibitor palbociclib increased autophagosome and then autolysosome levels in a time dependent fashion, did not reduce mTOR activity, and interacted with temsirolimus to kill...
September 5, 2018: Cancer Biology & Therapy
Ke Deng, Jiawei Shen, Wei Wang, Ming Li, Hong Li, Cheng Chen, Huan Zhao, Mei Zhang, Tian Xue, Qingsong Liu, Vivian Wai Yan Lui, Bo Hong, Wenchu Lin
Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high mortality. Effective new therapy for advanced SCLC patients is urgently needed. By screening a FDA-approved drug library, we identified a cardiac glycoside (CG), namely digoxin (an inhibitor of cellular Na+ /K+ ATPase pump), which was highly effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl supplement markedly enhanced the anti-tumor activities of digoxin in both in vitro and in vivo models of SCLC...
September 5, 2018: Cancer Biology & Therapy
John J Wilson, Kin-Hoe Chow, Nathan J Labrie, Jane A Branca, Thomas J Sproule, Bryant R A Perkins, Elise E Wolf, Mauro Costa, Grace Stafford, Christine Rosales, Kevin D Mills, Derry C Roopenian, Muneer G Hasham
Targeting the early steps of the glycolysis pathway in cancers is a well-established therapeutic strategy; however, the doses required to elicit a therapeutic effect on the cancer can be toxic to the patient. Consequently, numerous preclinical and clinical studies have combined glycolytic blockade with other therapies. However, most of these other therapies do not specifically target cancer cells, and thus adversely affect normal tissue. Here we first show that a diverse number of cancer models - spontaneous, patient-derived xenografted tumor samples, and xenografted human cancer cells - can be efficiently targeted by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor...
September 5, 2018: Cancer Biology & Therapy
Muhammad Bilal Abid, Jeremiah Stromich, Nathan D Gundacker
Chronic lymphocytic leukemia (CLL) is a disorder of B cells that affects humoral as well as cell-mediated immunity. Protection against cryptococcal infections is mounted by an intricate and synchronized interplay of both integral arms of immunity. Whether CLL or small molecule tyrosine kinase inhibitors are independently predisposing hosts to cryptococcal infections remain to be explored. Herein, we present a report of a patient who developed disseminated cryptococcosis while receiving ibrutinib therapy for CLL in the salvage setting...
August 27, 2018: Cancer Biology & Therapy
D Liu, Y Skomorovska, J Song, E Bowler, R Harris, M Ravasz, S Bai, M Ayati, K Tamai, M Koyuturk, X Yuan, Z Wang, Y Wang, R M Ewing
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a key step in the transformation of epithelial cells into migratory and invasive tumour cells. Intricate positive and negative regulatory processes regulate EMT. Many oncogenic signalling pathways can induce EMT, but the specific mechanisms of how this occurs, and how this process is controlled are not fully understood. METHODS: RNA-Seq analysis, computational analysis of protein networks and large-scale cancer genomics datasets were used to identify ELF3 as a negative regulator of the expression of EMT markers...
August 27, 2018: Cancer Biology & Therapy
Laurence Booth, Jane Lisa Roberts, Andrew Poklepovic, Paul Dent
Checkpoint immunotherapy antibodies have not shown efficacy in pancreatic adenocarcinoma. Pre-clinical studies and subsequently an on-going phase I trial have demonstrated the safety and efficacy of combinatorial radio-chemotherapy plus surgery in this malignancy, including the combination of sorafenib and vorinostat. The lethality of [sorafenib + vorinostat] was enhanced by gemcitabine. Exposure to [sorafenib + vorinostat] reduced the expression of β-catenin, ERBB1, BCL-XL and MCL-1, and the phosphorylation of AKT T308, AKT S473, GSK3 S9/21, mTORC1 and mTORC2...
August 24, 2018: Cancer Biology & Therapy
Shengnan Zhao, Yakun Zhang, Lei Wang, Li Yang, Liqun Zou, Fabao Gao
BACKGROUND: Adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap (AAV2-VEGF-Trap) has been reported to inhibit the growth of primary tumor as well as distant metastasis in 4T1 metastatic breast cancer models. The aim of this study was to investigate the inhibiting efficacy of AAV2-VEGF-Trap for glioma. METHODS: The intracranial transplanted model of glioma in rats was established. They were treated with AAV2-VEGF-Trap, bevacizumab (BEV), temozolomide (TMZ), TMZ combined with AAV2-VEGF-Trap, TMZ combined with BEV and the control group, respectively...
August 23, 2018: Cancer Biology & Therapy
Shujuan Zhou, Bo Xu, Liang Qi, Dongqin Zhu, Baorui Liu, Jia Wei
Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced gastric cancer patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. Here we conducted next-generation sequencing (NGS) on matched cfDNA from plasma, MPE and ascites from a stage-IV gastric cancer patient to identify potential therapeutic targets. In all three samples, we detected an amplification in the cellular-mesenchymal to epithelial transition factor (MET) gene, a truncation mutation in SMAD3 (p...
August 17, 2018: Cancer Biology & Therapy
Min Jin, Jun Cai, Xuan Wang, Tao Zhang, Yingchao Zhao
Ovarian cancer is a most common lethal gynecological malignant tumor, with a gradual increasing incidence throughout the world. The mainstay treatment is cytoreductive surgery followed by platinum-based chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors...
August 15, 2018: Cancer Biology & Therapy
You-Cai Zhu, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Zheng-Bo Song, Kai-Qi Du, Gang Chen, Tang-Feng Lv, Yong Song
In non-small cell lung cancer (NSCLC), driver gene alterations, such as EGFR, ALK, MET, and ROS1, are usually mutually exclusive. Few clinical cases with co-existing ROS1 fusion and de-novo MET amplification have been reported. In addition, the efficacy of crizotinib in Chinese patients with driver co-existing alterations is uncertain. A 65-year-old female was diagnosed with lung adenocarcinoma metastatic to the brain. She had sufficient tumor tissue for detection of the target gene; however, common driver gene mutations, such as EGFR-wild and ALK-negative, were not initially detected...
August 10, 2018: Cancer Biology & Therapy
Changlin Li, Haixia Xu, Lin Xiao, Haizhou Zhu, Guoan Zhang, Wei Wei, Kaizhi Li, Xiande Cao, Daqing Shen, Jeffrey Holzbeierlein, Benyi Li
OBJECTIVES: Distant metastasis is a critical factor for cancer-associated death. Our previous studies identified collapsin response mediator protein 4a (CRMP4a) as a metastasis suppressor in prostate cancers. Enhancing CRMP4 expression by promoter-targeted small activating RNAs reduced cell migration in vitro and abolished distal metastasis in mouse xenograft models. In this study, we investigated the mechanism for CRMP4a-mediated suppression of cell migration. METHODS: PC-3 cells were stably infected with lentiviruses expressing CRMP4a cDNA or a shRNA sequence...
August 6, 2018: Cancer Biology & Therapy
Yanqiu Song, Bailong Liu, Meng Guan, Min Liu
The treatment of intractable vasogenic brain edema (VBE) caused by tumor and irradiation is challenging. Traditional intervention strategy includes dehydration and glucocorticoids accompanied by obvious side effects and minor effects after long-term use. Novel treatment needs to be found urgently. Recently, vascular endothelial growth factor (VEGF)/VEGFR pathway has been revealed to be essential in VBE. Therefore, tyrosine kinase inhibitor (TKI) targeting VEGFR which blocks (VEGF)/VEGFR signal might be effective...
August 6, 2018: Cancer Biology & Therapy
Ji-Jin Yao, Lu-Lu Zhang, Tian-Sheng Gao, Ying-Lin Peng, Wayne R Lawrence, Wang-Jian Zhang, Fan Zhang, Guan-Qun Zhou, Si-Yang Wang, Ying Sun
PURPOSE: The benefits of additional use of nimotuzumab (NTZ) in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is largely unclear. We aim to compare LA-NPC treatment outcomes in patients that received CCRT with nimotuzumab (NTZ) to patients that received CCRT only. MATERIALS AND METHODS: Between October 2009 and January 2012, 31 previously untreated and newly diagnosed LA-NPC patients were administered CCRT (3 cycles of 100 mg/m2 cisplatin every third week with intensity-modulated radiotherapy) plus NTZ according to an IRB-approved institutional research protocol...
August 6, 2018: Cancer Biology & Therapy
Wang Jing, Haiyong Wang, Li Kong, Jinming Yu, Hui Zhu
Leptomeningeal metastases (LMs) were devastating metastatic complications of non-small cell lung cancer (NSCLC). Management of LMs relied on conventional therapy but with poor survival, lacking effective treatment strategies. We present the case of a 52-year-old female non-smoker with advanced lung adenocarcinoma and initially positive EGFR-mutation, who failed to the treatment of standard first-line chemotherapy (pemetrexed plus cisplatin) and bevacizumab (BEV), and maintenance therapy with pemetrexed plus BEV...
August 1, 2018: Cancer Biology & Therapy
Andreas Pircher, Martin Zieher, Andrea Eigentler, Renate Pichler, Georg Schäfer, Josef Fritz, Martin Puhr, Eberhard Steiner, Wolfgang Horninger, Helmut Klocker, Isabel Heidegger
BACKGROUND: We investigated the role of diabetes mellitus (DM) and the molecular mechanisms of antidiabetic drugs in prostate cancer (PCa). PATIENTS AND METHODS: 167 patients with both DM and PCa underwent radical prostatectomy (RPE). We divided our patient collective into "metformin" users, "insulin" users, "other antidiabetic drug" users and those with "no antidiabetic drug/diet only" (control group) and analyzed differences in PCa aggressiveness and laboratory parameters among treatment groups...
August 1, 2018: Cancer Biology & Therapy
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