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Translational Oncology

Ghayathri Balasundaram, Lu Ding, Xiuting Li, Amalina Binte Ebrahim Attia, Xose Luis Dean-Ben, Chris Jun Hui Ho, Prashant Chandrasekharan, Hui Chien Tay, Hann Qian Lim, Chee Bing Ong, Ralph P Mason, Daniel Razansky, Malini Olivo
PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO2 ) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO2 upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors...
August 10, 2018: Translational Oncology
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
Yanli Lin, Qixin Leng, Min Zhan, Feng Jiang
The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer-associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls...
August 8, 2018: Translational Oncology
Christina Demuth, Karen-Lise Garm Spindler, Julia S Johansen, Niels Pallisgaard, Dorte Nielsen, Estrid Hogdall, Benny Vittrup, Boe Sandahl Sorensen
Measuring total cell-free DNA (cfDNA) or cancer-specific mutations herein has presented as new tools in aiding the treatment of cancer patients. Studies show that total cfDNA bears prognostic value in metastatic colorectal cancer (mCRC) and that measuring cancer-specific mutations could supplement biopsies. However, limited information is available on the performance of different methods. Blood samples from 28 patients with mCRC and known KRAS mutation status were included. cfDNA was extracted and quantified with droplet digital polymerase chain reaction (ddPCR) measuring Beta-2 Microglobulin...
August 4, 2018: Translational Oncology
Eleni Vasilaki, Zoi Kanaki, Dimitrios J Stravopodis, Apostolos Klinakis
The Notch signaling pathway has been implicated in homeostasis and disease, including cancer, in various tissues. Moreover, it has been involved both in stem cell maintenance and differentiation, in a context-dependent manner. Stem/progenitor cells, on the other hand, have long been suspected to be the cells of origin in various malignancies. In order to gain insight in the role of the Notch ligand Dll1 in mouse development, we generated a knock-in line expressing an inducible Cre recombinase. We have employed in vivo approaches in mice to genetically mark rare subpopulations of cells expressing Dll1 in various adult tissues...
August 3, 2018: Translational Oncology
Bing Zhu, Pei Zhang, Mulin Liu, Congqiao Jiang, Hao Liu, Jun Fu
BACKGROUND: COP9 signalosome subunit 2 (CSN2) is believed to be involved in human cancer, but its prognostic significance in colorectal cancer (CRC) has not been elucidated. PATIENTS AND METHODS: We retrospectively analyzed the expression of CSN2 andCD8+ tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) status in 267 paraffin-embedded specimens using immunohistochemistry in a training cohort. A number of risk factors were used to form nomograms to evaluate survival, and Harrell's concordance index (C-index) was used to evaluate the predictive accuracy...
July 31, 2018: Translational Oncology
Shailesh M Advani, Pragati Advani, Stacia M DeSantis, Derek Brown, Helena M VonVille, Michael Lam, Jonathan M Loree, Amir Mehrvarz Sarshekeh, Jan Bressler, David S Lopez, Carrie R Daniel, Michael D Swartz, Scott Kopetz
BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods...
July 30, 2018: Translational Oncology
Zehang Jiang, Zhixian Liu, Mengyuan Li, Cai Chen, Xiaosheng Wang
Although immunotherapy continues to demonstrate efficacy in a variety of refractory cancers, currently, no any immunotherapeutic strategy is clinically used for gastric cancer (GC) except its microsatellite instable subtype. Thus, it is important to identify molecular biomarkers for predicting the responders to GC immunotherapy. TP53 mutations frequently occur in GC and are associated with unfavorable clinical outcomes in GC. We performed a comprehensive characterization of the associations between TP53 mutations and immune activities in GC based on two large-scale GC cancer genomics data...
July 27, 2018: Translational Oncology
K Veskimäe, M Scaravilli, W Niininen, H Karvonen, S Jaatinen, M Nykter, T Visakorpi, J Mäenpää, D Ungureanu, S Staff
Ovarian cancer has the highest mortality rate of all gynecologic malignancies. Identification of new biomarkers is highly needed due to its late diagnosis and high recurrence rate. The objective of this study was to identify mechanisms of therapy resistance and potential biomarkers by analyzing mRNA and protein expression from samples derived from patients with platinum-sensitive and -resistant ovarian cancer (total cohort n = 53). The data revealed new candidates for targeted therapies, such as GREB1 and ROR2...
July 26, 2018: Translational Oncology
ChuanLiang Cui, Li Zhou, Bin Lian, Lu Si, XiNan Sheng, ZhiHong Chi, Yan Kong, Xuan Wang, BiXia Tang, LiLi Mao, SiMing Li, Jie Dai, XieQiao Yan, Xue Bai, Jun Guo
OBJECTIVE: Asian melanoma patients, predominantly comprised of acral and mucosal subtypes, might not benefit from immunotherapy and targeted therapy as much as Caucasian patients. Novel treatment strategies are demanded after conventional treatment failure. This was a prospective, single-arm, and single-center dose escalation study to investigate the safety and preliminary efficacy of apatinib combined with temozolomide in heavily treated advanced melanoma patients. METHODS: Patients were sequentially admitted to four dose-escalating groups of apatinib and temozolomide (three cases in each group) using a traditional 3 + 3 dose escalation design method...
July 26, 2018: Translational Oncology
Wenhan Deng, Alexandra Clipson, Hongxiang Liu, Yuanxue Huang, Rachel Dobson, Ming Wang, Peter Johnson, Ming-Qing Du
Several newly developed drugs including JQ1 (BET inhibitor), ABT199 (BCL2 inhibitor), and bortezomib (proteasome inhibitor) may offer novel therapeutic strategies for aggressive diffuse large B-cell lymphoma (DLBCL). We tested these drugs together with doxorubicin in a series of combinations in 16 DLBCL cell lines including 4 ABC-DLBCL (OCI-Ly3, OCI-Ly10, SUDHL2, RIVA) and 12 GCB-DLBCL lines (OCI-Ly4, OCI-Ly18, BJAB, SUDHL4, SUDHL6, SUDHL10, DB, PR1, VAL, SC1, Karpas-231, Karpas-422). Among these cell lines, ABT199 and doxorubicin, and to a lesser extent JQ1 and bortezomib, showed high variations in their ED50 values...
July 25, 2018: Translational Oncology
Jacqueline V Brady, Ryan M Troyer, Stephen A Ramsey, Haley Leeper, Liping Yang, Claudia S Maier, Cheri P Goodall, Carl E Ruby, Hassan A M Albarqi, Oleh Taratula, Shay Bracha
Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease and can be found in blood. The exosomal proteomic cargo can often be traced to the cells from which they originated, reflecting the physiological status of these cells. The similarities between cancer exosomes and the tumor cells they originate from exhibit the potential of these vesicles as an invaluable target for liquid biopsies. Exosomes were isolated from the serum of eight osteosarcoma-bearing dogs, five healthy dogs, and five dogs with traumatic fractures...
July 24, 2018: Translational Oncology
Anette Hauge, Catherine S Wegner, Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
Antiangiogenic treatment (AAT) used in combination with radiation therapy or chemotherapy is a promising strategy for the treatment of several cancer diseases. The vascularity and oxygenation of tumors may be changed significantly by AAT, and consequently, a noninvasive method for monitoring AAT-induced changes in these microenvironmental parameters is needed. The purpose of this study was to evaluate the potential usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI). DW-MRI was conducted with a Bruker Biospec 7...
July 20, 2018: Translational Oncology
Xueyan Wang, Ye Xu, Weiqing Tang, Lingxiang Liu
BACKGROUND: The role of radiotherapy (RT) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains controversial. Therefore, we conducted a meta-analysis to comprehensively evaluate the efficacy and safety of RT plus EGFR-TKIs in those patients. MATERIALS AND METHODS: Relevant literatures published between 2012 and 2017 were searched. Objective response rate(ORR), disease control rate (DCR), overall survival (OS), intracranial progression-free survival (I-PFS) and adverse events (AEs) were extracted...
July 19, 2018: Translational Oncology
Yu-Feng Yang, Ying-Hua Pan, Qiu-Hong Tian, Dan-Chun Wu, Shu-Guang Su
Dysregulation of chromobox proteins contributes to the progression of human diseases. CBX1 has been implicated in epigenetic control of chromatin structure and gene expression, but its role in human cancers remains largely unknown. Here we show that CBX1 exhibits oncogenic activities in hepatocellular carcinoma (HCC) and indicates poor outcomes. The expression of CBX1 was noticeably increased, at both mRNA and protein levels, in HCC tissues and cell lines, compared with the nontumorous ones. High CBX1 expression was significantly associated with larger tumor size, poor tumor differentiation and tumor vascular invasion...
July 18, 2018: Translational Oncology
Entesar Dalah, An Tai, Kiyoko Oshima, William A Hall, Beth Erickson, X Allen Li
PURPOSE: Performance of anatomical metrics of Response Evaluation Criteria in Solid Tumors (RECIST1.1) versus Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST1.0) for neoadjuvant chemoradiation (nCR) of pancreatic adenocarcinoma was evaluated based on the pathological treatment response (PTR) data. METHODS AND MATERIALS: The pre- and post-nCR CT and PET data for 14 patients with resectable or borderline resectable pancreatic head adenocarcinoma treated with nCR followed by surgery were retrospectively analyzed...
July 13, 2018: Translational Oncology
Dong-Liu Miao, Wei Song, Jun Qian, Zhi-Gang Zhu, Qiong Wu, Chang-Guang Lv, Lei Chen
BACKGROUND: The objective of current study was to develop and validate a nomogram to predict overall survival in pancreatic neuroendocrine tumors (PNETs). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with PNETs between 2004 and 2015. Patients were randomly separated into the training set and the validation set. Cox regression model was used in training set to obtain independent prognostic factors to develop a nomogram for predicting overall survival (OS)...
July 12, 2018: Translational Oncology
Sophie Sixou, Katharina Müller, Stéphan Jalaguier, Christina Kuhn, Nadia Harbeck, Doris Mayr, Jutta Engel, Udo Jeschke, Nina Ditsch, Vincent Cavaillès
New markers are needed to improve diagnosis and to personalize treatments for patients with breast cancer (BC). Receptor-interacting protein of 140 kDa (RIP140) and ligand-dependent corepressor (LCoR), two transcriptional co-regulators of estrogen receptors, strongly interact in BC cells. Although their role in cancer progression has been outlined in the last few years, their function in BC has not been elucidated yet. In this study, we investigated RIP140 and LCoR localization (cytoplasm vs nucleus) in BC samples from a well-characterized cohort of patients (n = 320)...
July 11, 2018: Translational Oncology
Tianhang Luo, Jiangman Zhao, Zhengmao Lu, Jianwei Bi, Tao Pang, Hangtian Cui, Biao Yang, Wushuang Li, Yu Wang, Shouxin Wu, Xuchao Xue
Previous studies proved that long noncoding RNAs (lncRNAs) play important role in human cancer. However, the knowledge of genome scale expression of lncRNAs and their potential biological function in gastric cancer is still lacking. Next generation RNA sequencing (RNA-seq) was performed on tumor tissues and matched adjacent normal tissues of six diffuse gastric cancer (DGC) patients. Then we performed a comprehensive analysis on lncRNAs and mRNA. Fifty-eight lncRNAs were upregulated and 54 lncRNAs were downregulated in diffuse gastric cancer tissue compared with adjacent tissue...
July 10, 2018: Translational Oncology
Alexey Surov, Daniel T Ginat, Tchoyoson Lim, Teresa Cabada, Ozdil Baskan, Stefan Schob, Hans Jonas Meyer, Georg Alexander Gihr, Diana Horvath-Rizea, Gordian Hamerla, Karl Titus Hoffmann, Andreas Wienke
Low grade meningiomas have better prognosis than high grade meningiomas. The aim of this study was to measure apparent diffusion coefficient (ADC) histogram analysis parameters in different meningiomas in a large multicenter sample and to analyze the possibility of several parameters for predicting tumor grade and proliferation potential. Overall, 148 meningiomas from 7 institutions were evaluated in this retrospective study. Grade 1 lesions were diagnosed in 101 (68.2%) cases, grade 2 in 41 (27.7%) patients, and grade 3 in 6 (4...
July 10, 2018: Translational Oncology
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