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Liangkun Pan, Qiang Zheng, Yu Chen, Rui Yang, Yanyan Yang, Zhongjun Li, Xiangbao Meng
Indoleamine 2,3-dioxygenase 1 (IDO1) mediated kynurenine pathway of tryptophan degradation is identified as an appealing and novel target in immunotherapy for the treatment of cancer. In this study, a novel series of naphthoquinone derivatives were synthesized, characterized and evaluated for their inhibitory activities against IDO1, and their structure-activity relationship was investigated. Among them, compounds T16, T44, T47, T49, T53 and T54 displayed potent IDO1 inhibitory activities with IC50 values ranging between 18 and 61 nM, which are more potent than INCB024360 undergoing clinical trial III evaluation...
August 7, 2018: European Journal of Medicinal Chemistry
Xinbo Xu, Heng Liu, Neil Gross, Dongmin Wei, Ye Qian, Wenming Li, Peng Wei, Guojun Li, Fenghua Zhang, Zheng Yang, Dapeng Lei, Xinliang Pan
Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers. These tumors often have an aggressive clinical outcome characterized by local invasion and regional nodal metastasis. Upregulated miRNAs might be useful as biomarkers for prognosis and molecular targets for these tumors. We determined tumor expression of candidate miRNAs using microarray in 8 HC patients and validated in 372 HC patients. We also used paired tumorous and mucosal tissue to verify the miRNA expression. Log-rank test and Cox model were used to evaluate the survival; and Harrell's C-index was used to compare concordance of Cox models...
August 10, 2018: Translational Oncology
Afu Fu, Yu Ming Peh, Weida Ngan, Na Wei, Kathy Qian Luo
Treating systemic metastases at the micrometastatic stage is a potential strategy to inhibit cancer metastasis. This study aims to establish an apoptosis sensor-based platform for rapid, effective, and non-invasive identification of drugs that can inhibit the proliferation of micrometastatic cancer cells. We stably transfected the plasmid DNA encoding the fluorescence resonance energy transfer (FRET)-based caspase-3 sensor into highly metastatic melanoma B16F10 cells. The resulting B16F10-C3 cells were applied for screening of anti-proliferative and pro-apoptotic drugs in two-dimensional (2D) monolayer, three-dimensional (3D) spheroids, and zebrafish xenotransplantation tumors...
August 13, 2018: Biotechnology and Bioengineering
Jianping Lu, Juan Xu, Junyi Li, Tao Pan, Jing Bai, Liqiang Wang, Xiyun Jin, Xiaoyu Lin, Yunpeng Zhang, Yongsheng Li, Nidhi Sahni, Xia Li
Epigenetic alterations, a well-recognized cancer hallmark, are driven by chromatin regulators (CRs). However, little is known about the extent of CR deregulation in cancer, and less is known about their common and specialized roles across various cancers. Here, we performed genome-wide analyses and constructed molecular signatures and network profiles of functional CRs in over 10 000 tumors across 33 cancer types. By integration of DNA mutation, genome-wide methylation, transcriptional/post-transcriptional regulation, and protein interaction networks with clinical outcomes, we identified CRs associated with cancer subtypes and clinical prognosis as potential oncogenic drivers...
August 8, 2018: Nucleic Acids Research
A L F V Assumpção, Z Lu, K W Marlowe, K S Shaffer, X Pan
Canine diffuse large B-cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule NEDD8-activating enzyme inhibitor. In human activated B-cell-like (ABC) diffuse large B-cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage and G1 cell cycle arrest by inhibiting the nuclear factor-κB (NF-κB) pathway...
August 13, 2018: Veterinary and Comparative Oncology
István Hajdú, József Kardos, Balázs Major, Gabriella Fabó, Zsolt Lőrincz, Sándor Cseh, György Dormán
Lysyl oxidase (LOX) enzymes as potential drug targets maintain constant attention in the therapy of fibrosis, cancer and metastasis. In order to measure the inhibitory activity of small molecules on the LOX enzyme family members a fluorometric activity screening method was developed. During assay validation, previously reported non-selective small inhibitor molecules (BAPN, MCP-1, thiram, disulfiram) were investigated on all of the major LOX enzymes. We confirmed that MCP-1, thiram, disulfiram are in fact pan-inhibitors, while BAPN inhibits only LOX-like enzymes (preferably LOX-like-protein-2, LOXL2) in contrast to the previous reports...
July 6, 2018: Bioorganic & Medicinal Chemistry Letters
Hanibal Bohnenberger, Lars Kaderali, Philipp Ströbel, Diego Yepes, Uwe Plessmann, Neekesh V Dharia, Sha Yao, Carina Heydt, Sabine Merkelbach-Bruse, Alexander Emmert, Jonatan Hoffmann, Julius Bodemeyer, Kirsten Reuter-Jessen, Anna-Maria Lois, Leif Hendrik Dröge, Philipp Baumeister, Christoph Walz, Lorenz Biggemann, Roland Walter, Björn Häupl, Federico Comoglio, Kuan-Ting Pan, Sebastian Scheich, Christof Lenz, Stefan Küffer, Felix Bremmer, Julia Kitz, Maren Sitte, Tim Beißbarth, Marc Hinterthaner, Martin Sebastian, Joachim Lotz, Hans-Ulrich Schildhaus, Hendrik Wolff, Bernhard C Danner, Christian Brandts, Reinhard Büttner, Martin Canis, Kimberly Stegmaier, Hubert Serve, Henning Urlaub, Thomas Oellerich
Patients with head-and-neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types...
August 10, 2018: EMBO Molecular Medicine
Jianzhong Su, Yung-Hsin Huang, Xiaodong Cui, Xinyu Wang, Xiaotian Zhang, Yong Lei, Jianfeng Xu, Xueqiu Lin, Kaifu Chen, Jie Lv, Margaret A Goodell, Wei Li
BACKGROUND: Cancers have long been recognized to be not only genetically but also epigenetically distinct from their tissues of origin. Although genetic alterations underlying oncogene upregulation have been well studied, to what extent epigenetic mechanisms, such as DNA methylation, can also induce oncogene expression remains unknown. RESULTS: Here, through pan-cancer analysis of 4174 genome-wide profiles, including whole-genome bisulfite sequencing data from 30 normal tissues and 35 solid tumors, we discover a strong correlation between gene-body hypermethylation of DNA methylation canyons, defined as broad under-methylated regions, and overexpression of approximately 43% of homeobox genes, many of which are also oncogenes...
August 10, 2018: Genome Biology
Maria Cosenza, Samantha Pozzi
Histone deacetylases (HDACs) are master regulators of chromatin remodeling, acting as epigenetic regulators of gene expression. In the last decade, inhibition of HDACs has become a target for specific epigenetic modifications related to cancer development. Overexpression of HDAC has been observed in several hematologic malignancies. Therefore, the observation that HDACs might play a role in various hematologic malignancies has brought to the development of HDAC inhibitors as potential antitumor agents. Recently, the class IIb, HDAC6, has emerged as one potential selective HDACi...
August 9, 2018: International Journal of Molecular Sciences
Majid Momeny, Haniyeh Eyvani, Farinaz Barghi, Seyed H Ghaffari, Sepehr Javadikooshesh, Robab H Jamadi, Fatemeh Esmaeili, Zivar Alishahi, Azam Zaghal, Davood Bashash, Fazel S Samani, Parisa Ghaffari, Ahmad R Dehpour, Seyyed M Tavangar, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination are the major reasons for low survival rate in the patients. The bromodomain and extraterminal domain (BET) proteins are known as epigenetic 'readers,' and their inhibitors are novel epigenetic strategies for cancer treatment. Accumulating body of evidence indicates that epigenetic modifications have critical roles in development of EOC, and overexpression of the BET family is a key step in the induction of important oncogenes...
August 9, 2018: Anti-cancer Drugs
Jung Soo Lee, Hye Sung Won, Der Sheng Sun, Ji Hyung Hong, Yoon Ho Ko
BACKGROUND: The potential prognostic value of tumor-infiltrating lymphocytes (TILs) in gastric cancer remains controversial. This meta-analysis examines the association between TILs and survival outcomes in gastric cancer. METHODS: Twenty-two eligible studies were identified using the PubMed and Google Scholar databases. The combined sample size of the 22 studies was 2941, and the median sample size of the individual studies was 122 patients (52-220). The main clinical outcomes examined were overall cancer survival (OCS) and overall cancer relapse-free survival (OCRFS)...
August 2018: Medicine (Baltimore)
Xiaoyuan Gao, Yang Zhang, Fei Yuan, Bei Ding, Qianchen Ma, Wenjie Yang, Jing Yan, Lianjun Du, Baisong Wang, Fuhua Yan, Martin Sedlmair, Zilai Pan, Huan Zhang
PURPOSE: Pathologic response to neoadjuvant chemotherapy is a prognostic factor in many cancer types. However, the existing evaluative criteria are deficient. We sought to prospectively evaluate the total iodine uptake derived from dual-energy computed tomography (DECT) in predicting treatment efficacy and progression-free survival (PFS) time in gastric cancer after neoadjuvant chemotherapy. METHODS: From October 2012 to December 2015, 44 patients with locally advanced gastric cancer were examined with DECT 1 week before and three cycles after neoadjuvant chemotherapy...
August 9, 2018: Journal of Cancer Research and Clinical Oncology
Hans Ligtenberg, Stefan M Willems, Lilian N Ruiter, Elise Anne Jager, Chris H J Terhaard, Cornelis P J Raaijmakers, Marielle E P Philippens
Background: For accurate target definition, we determined margins for the clinical target volume (CTV) for laryngeal and hypopharyngeal cancer in computed tomography (CT, 4.3 mm), magnetic resonance imaging (MR, 6.1 mm) and fluorodeoxyglucose (FDG)-positron emission tomography (PET, 5.2 mm). Previously, we used Hematoxylin-eosin (HE) stained whole-mount sections of total laryngectomy specimens as gold standard to define CTV margins. In the present study, we verified the HE-based tumor delineation with staining for pan-cytokeratin, specific for squamous cell carcinoma...
August 2018: Clinical and Translational Radiation Oncology
Shaokun Pan, Tian Yu, Yanchun Wang, Renquan Lu, Huijie Wang, Youhua Xie, Xiping Feng
At least 12% of human cancers are caused by virus infection. To understand whether other viruses are associated with human cancers, a viral metagenomics approach was used to analyze the composition of the viral communities of the serum of the patients with Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma. In this report, a human anellovirus TTMV named TTMV-SH was discovered from three patients with HL. The complete genome of TTMV-SH is 2812nt in length. Phylogenetic analysis based on ORF1 indicated that TTMV-SH of the 11 isolates cluster with TTMV strain TLMV-CBD231 sharing only 60...
2018: Frontiers in Microbiology
Cong Wang, Yuepeng Ke, Shaoyou Liu, Sharon Pan, Ziying Liu, Hui Zhang, Zhichao Fan, Changyi Zhou, Junchen Liu, Fen Wang
Initiation of expression of fibroblast growth factor receptor 1 (FGFR1) concurrent with loss of FGFR2 expression is a well-documented event in the progression of prostate cancer (PCa). Although it is known that some FGFR isoforms confer advantages in cell proliferation and survival, the mechanism by which the subversion of different FGFR isoforms contributes to PCa progression is incompletely understood. Here, we report that fibroblast growth factor (FGF) promotes NF-κB signaling in PCa cells and that this increase is associated with FGFR1 expression...
August 9, 2018: Journal of Biological Chemistry
Yiping Weng, Yifei Shen, Yunjie He, Xiaohui Pan, Jingwen Xu, Yuqing Jiang, Qiang Zhang, Shenyu Wang, Fanqi Kong, Shujie Zhao, Dong Zhou, Yunkun Zhang
Blocking aerobic glycolysis has been proposed as an attractive therapeutic strategy for impairing the proliferation of cancer cells. However, the underlying mechanisms are poorly understood. Here, we show that miR-15b-5p was downregulated in osteosarcoma (OS) and that lower expression of miR-15b-5p promoted proliferation and contributed to the Warburg effect in OS cells. Mechanistically, miR-15b-5p acted as a tumor suppressor in OS by directly targeting pyruvate dehydrogenase kinase-4 and inhibiting its expression...
August 6, 2018: Biochemical and Biophysical Research Communications
Imane El Dika, David H Ilson
Gastrointestinal (GI) cancers altogether represent the most common cancer type. HER2 is found to be present in nearly all histologic types of GI cancers in variable degrees of expression. Over the last decade, substantial advances have been made in targeting HER2-positive cancers. Areas covered: The present review summarizes the current progress and future directions for HER2 targeted therapies in GI cancers, including esophagogastric, pancreaticobiliary, and colon cancers. To date trastuzumab is the only anti-HER2 therapy approved for metastatic esophagogastric adenocarcinoma...
August 9, 2018: Expert Review of Anticancer Therapy
Hehai Pan, Adam Strickland, Vedavathi Madhu, Zariel I Johnson, Saswati N Chand, Jonathan R Brody, Andrzej Fertala, Zhaomin Zheng, Irving M Shapiro, Makarand V Risbud
Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic signaling in several cancers, however, its function in the disc is unknown. HuR did not show cytoplasmic translocation in hypoxia and evidenced levels of Hif-1α and HIF-targets in NP cells. RNA-Sequencing data revealed important extracellular matrix-related genes including several collagens, MMPs, aggrecan, Tgf-β3 and Sdc4 were regulated by HuR. Analysis of HuR-silenced NP cells confirmed that HuR maintained expression of these matrix genes...
August 6, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
Yumiko Azuma, Takahiko Tokuda, Yukie Kushimura, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Yasushi Iwasaki, Mari Yoshida, Duojia Pan, Hideki Yoshida, Masamitsu Yamaguchi
Mutations in the Fused in Sarcoma (FUS) gene have been identified in familial ALS in human. Drosophila contains a single ortholog of human FUS called Cabeza (Caz). We previously established Drosophila models of ALS targeted to Caz, which developed the locomotive dysfunction and caused anatomical defects in presynaptic terminals of motoneurons. Accumulating evidence suggests that ALS and cancer share defects in many cellular processes. The Hippo pathway was originally discovered in Drosophila and plays a role as a tumor suppressor in mammals...
August 6, 2018: Experimental Cell Research
Alireza Sanchooli, Khosrow Aghayipour, Bahman Abedi Kiasari, Alireza Samarbaf-Zadeh, Ataollah Ghadiri, Manoocher Makvandi
Human papillomavirus 16 is considered a causative agent of genital cancers. Since there is no decisive treatment, the only approach is vaccination of high-risk group. Due to the high cost, the current HPV vaccines are not affordable in developing countries. This study aimed to produce a chimeric L1/L2 protein in Pichia Pastoris system. To develop the VLPs retrieved from chimeric L1/L2 protein HPV-16, first, a cross-neutralizing epitope of HPV-16 L2 gene was inserted into L1 HPV-16 gene. The chimeric L1/L2 HPV-16 was inserted in pPICZA plasmid and expressed in Pichia pastoris (P...
August 9, 2018: Protein and Peptide Letters
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