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Translational Oncology

Yuri Choi, Yeo-Jin Won, Sojeong Lee, Ahrong Kim, Younggeum Kim, Won-Young Park, Hong-Jae Jo, Geun Am Song, Chae Hwa Kwon, Do Youn Park
NTRK1 gene fusions, the targets of multikinase inhibitors, are promising therapeutic targets for colorectal cancer (CRC). However, screening methods for detecting NTRK1 gene fusions in CRC tissues have not been reported. In this study, we investigated the potential use of immunohistochemistry (IHC) for detecting NTRK1 gene fusions. We performed and compared IHC with fluorescence in situ hybridization (FISH) in 80 CRC patients. TrkA immunostaining was observed to be both membranous and cytoplasmic and was scored semiquantitatively using staining intensity and proportions...
April 21, 2018: Translational Oncology
Marise R Heerma van Voss, Kai Kammers, Farhad Vesuna, Justin Brilliant, Yehudit Bergman, Saritha Tantravedi, Xinyan Wu, Robert N Cole, Andrew Holland, Paul J van Diest, Venu Raman
DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control...
April 20, 2018: Translational Oncology
Yih-Lin Chung, Mei-Ling Wu
The persistence of hepatitis B surface antigen (HBsAg) is a risk factor for the development of steatosis-associated tumors in chronic hepatitis B virus (HBV) infection, yet little is known about the metabolic link with this factor. We correlated HBV-related pathogenesis in genetically engineered mice and human carriers with metabolic proteomics and lipogenic gene expression profiles. The immunohistochemistry showed that the promyelocytic leukemia protein (PML, a tumor suppressor involved in genome maintenance and fatty acid oxidation), being inversely influenced by the dynamic HBsAg levels from acute phase to seroclearance, appeared as a lipo-metabolic switch linking HBsAg-induced steatosis (lipogenesis) to HBsAg-lost fat-burning hepatocarcinogenesis (lipolysis)...
April 20, 2018: Translational Oncology
Matthew T McKenna, Jared A Weis, Amy Brock, Vito Quaranta, Thomas E Yankeelov
Medical oncology is in need of a mathematical modeling toolkit that can leverage clinically-available measurements to optimize treatment selection and schedules for patients. Just as the therapeutic choice has been optimized to match tumor genetics, the delivery of those therapeutics should be optimized based on patient-specific pharmacokinetic/pharmacodynamic properties. Under the current approach to treatment response planning and assessment, there does not exist an efficient method to consolidate biomarker changes into a holistic understanding of treatment response...
April 16, 2018: Translational Oncology
Aleksandra Markiewicz, Anna Nagel, Jolanta Szade, Hanna Majewska, Jaroslaw Skokowski, Barbara Seroczynska, Tomasz Stokowy, Marzena Welnicka-Jaskiewicz, Anna J Zaczek
Intratumoral heterogeneity of breast cancer remains a major challenge in successful treatment. Failure of cancer therapies can also be accredited to inability to systemically eradicate cancer stem cells (CSCs). Recent evidence points to the role of epithelial-mesenchymal transition (EMT) in expanding the pool of tumor cells with CSCs features. Thus, we assessed expression level as well as heterogeneity of CSCs markers in primary tumors (PT), lymph node metastasis (LNM), and circulating tumor cells (CTCs)-enriched blood fractions in order to correlate them with signs of EMT activation as well as clinicopathological data of breast cancer patients...
April 13, 2018: Translational Oncology
Sandra Santasusagna, Isabel Moreno, Alfons Navarro, Joan J Castellano, Francisco Martinez, Raquel Hernández, Carmen Muñoz, Mariano Monzo
BACKGROUND: The analysis of exosomes in blood obtained from the tumor-draining mesenteric vein (MV) can identify tumor biomarkers before they reach target organs and form the premetastatic niche where circulating tumor cells can anchor. Our group has recently shown that microRNAs in plasma from the MV-but not the peripheral vein (PV)-have been related to liver metastases in colon cancer (CC) patients. Here we examine the exosomal protein cargo in plasma from the MV and paired PV in 31 CC patients...
April 13, 2018: Translational Oncology
Bin Liu, Hai Yang, Leila Taher, Axel Denz, Robert Grützmann, Christian Pilarsky, Georg F Weber
Pancreatic cancer is the fourth leading cause for cancer-related death, and early diagnosis is one key to improve the survival rate of this disease. Molecular biomarkers are an important method for diagnostic use in pancreatic cancer. We used data from three mRNA microarray datasets and a microRNA dataset (GSE16515, GSE15471, GSE28735, and GSE41372) to identify potential key genes. Differentially expressed genes (DEGs) and microRNAs (DEMs) were identified. Functional, pathway enrichment, and protein-protein interaction analyses were performed on common DEGs across all datasets...
April 5, 2018: Translational Oncology
Yang Song, Qing Wang, Desheng Wang, Junqiang Li, Jing Yang, Hong Li, Xiang Wang, Xuerong Jin, Ruirui Jing, Jing-Hua Yang, Haichuan Su
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a high mortality rate and poor prognosis. However, little is known concerning the molecular mechanism of PDAC at the proteomics level. Here we report a proteomics analysis of PDAC tumor and adjacent tissues by shotgun proteomics followed by label-free quantification, and in total, 3031 and 3306 proteins were identified in three pairs of PDAC tumor and adjacent tissues, respectively; 40 of them were differentially expressed for at least three-fold in PDAC tumor tissues...
April 5, 2018: Translational Oncology
Nam-Chul Jung, Jun-Ho Lee, Kwang-Hoe Chung, Yi Sub Kwak, Dae-Seog Lim
As a treatment for solid tumors, dendritic cell (DC)-based immunotherapy has not been as effective as expected. Here, we review the reasons underlying the limitations of DC-based immunotherapy for solid tumors and ask what can be done to improve immune cell-based cancer therapies. Several reports show that, rather than a lack of immune induction, the limited efficacy of DC-based immunotherapy in cases of renal cell carcinoma (RCC) likely results from inhibition of immune responses by tumor-secreted TGF-β and an increase in the number of regulatory T (Treg) cells in and around the solid tumor...
April 5, 2018: Translational Oncology
Perla Pérez-Treviño, Héctor Hernández-De la Cerda, Jorge Pérez-Treviño, Oscar Raúl Fajardo-Ramírez, Noemí García, Julio Altamirano
Patients with breast cancer (BC) overexpressing HER2 (HER2+) are selected for Trastuzumab treatment, which blocks HER2 and improves cancer prognosis. However, HER2+ diagnosis, by the gold standard, immunohistochemistry, could lead to errors, associated to: a) variability in sample manipulation (thin 2D sections), b) use of subjective algorithms, and c) heterogeneity of HER2 expression within the tissue. Therefore, we explored HER2 3D detection by multiplexed imaging of Affibody-Quantum Dots conjugates (Aff-QD), ratiometric analysis (RMAFI ) and thresholding, using BC multicellular tumor spheroids (BC-MTS) (~120 μm of diameter) as 3D model of BC...
April 4, 2018: Translational Oncology
Martyna Krzykawska-Serda, Mahdi S Agha, Jason Chak-Shing Ho, Matthew J Ware, Justin J Law, Jared M Newton, Lam Nguyen, Steven A Curley, Stuart J Corr
Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy...
April 2, 2018: Translational Oncology
Aung Ko Ko Oo, Anna Sanchez Calle, Neha Nair, Hafizah Mahmud, Arun Vaidyanath, Junya Yamauchi, Aprilliana Cahya Khayrani, Juan Du, Md Jahangir Alam, Akimasa Seno, Akifumi Mizutani, Hiroshi Murakami, Yoshiaki Iwasaki, Ling Chen, Tomonari Kasai, Masaharu Seno
Previously, we have succeeded in converting induced pluripotent stem cells (iPSCs) into cancer stem cells (CSCs) by treating the iPSCs with conditioned medium of Lewis lung carcinoma (LLC) cells. The converted CSCs, named miPS-LLCcm cells, exhibited the self-renewal, differentiation potential, and potential to form malignant tumors with metastasis. In this study, we further characterized miPS-LLCcm cells both in vivo and in vitro. The tumors formed by subcutaneous injection showed the structures with pathophysiological features consisting of undifferentiated and malignant phenotypes generally found in adenocarcinoma...
April 2, 2018: Translational Oncology
Cristina Mansilla, Elena Soria, Miren Vallejo, Alberto Valiente, Aránzazu Perez-Juana, Amaya Zabalza, Guillermina Hurtado, Francisco Sala, Natalia Ramírez
Multiple myeloma (MM) is a very heterogeneous disease, characterized by multiple cytogenetic aberrations on plasma cells (PC) that have been traditionally used to predict the outcome of the disease. A mayor issue on the analysis of PC is the sometimes low infiltration of these cells in the bone marrow that hampers cytogenetic studies. To solve this problem we have optimized a selection strategy based on PC immunomagnetic isolation that has allowed us to lower to 1% the minimal PC infiltration requirement without loss of purity, enabling to perform genetic analysis...
March 28, 2018: Translational Oncology
Fabio Galbusera, Zhihui Qian, Gloria Casaroli, Tito Bassani, Francesco Costa, Benedikt Schlager, Hans-Joachim Wilke
Vertebral fractures associated with the loss of structural integrity of neoplastic vertebrae are common, and determined to the deterioration of the bone quality in the lesion area. The prediction of the fracture risk in metastatically involved spines can guide in deciding if preventive solutions, such as medical prophylaxis, bracing, or surgery are indicated for the patient. In this study, finite element models of 22 thoracolumbar vertebrae were built based on CT scans of three spines, covering a wide spectrum of possible clinical scenarios in terms of age, bone quality and degenerative features, taking into account the local material properties of bone tissue...
March 28, 2018: Translational Oncology
Hua Zhang, Erich Sturgis, Lijun Zhu, Zhongming Lu, Ye Tao, Hongliang Zheng, Guojun Li
Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1 pathway. A polymorphism in the 3' UTR of E2F1 gene may disrupt a binding site for miRNA and may affect its transcription level, thus modifying the susceptibility to radiotherapy and outcomes through this pathway. We evaluated the association of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with risk of recurrence of SCCOP in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate the associations...
March 22, 2018: Translational Oncology
Lin Chunhua, Haiwei Zhao, Huishan Zhao, Youyi Lu, Jitao Wu, Zhenli Gao, Guojun Li, Yulian Zhang, Ke Wang
Prostate cancer antigen 3 (PCA3) is one of the most promising genes currently investigated as a specific tumor biomarker for the diagnosis of prostate cancer. The purpose of this study was to investigate PCA3 gene expression in peripheral blood of prostate cancer (PCa) and benign prostate hyperplasia (BPH), and further to assess its clinical significance. We determined the copies of PCA3 mRNA in peripheral blood of PCa and BPH from 115 samples (PCa, n=78; BPH, n=37) using a quantitative reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) with TaqMan assay...
March 21, 2018: Translational Oncology
Pengwei Yan, Huanfeng Zhu, Li Yin, Lijun Wang, Peng Xie, Jinjun Ye, Xuesong Jiang, Xia He
Lung cancer is notorious for high morbidity and mortality around the world. Interleukin (IL)-8, a proinflammatory chemokine with tumorigenic and proangiogenic effects, promotes lung cancer cells growth and migration and contributes to cell aggressive phenotypes. Integrin αvβ6 is a receptor of transmembrane heterodimeric cell surface adhesion, and its overexpression correlates with poor survival from non-small cell lung cancer. However, the cross talk between αvβ6 and IL-8 in lung cancer has not been characterized so far...
March 20, 2018: Translational Oncology
Tao Xu, Hongxiang Wang, Xiaoquan Huang, Weiqing Li, Qilin Huang, Yong Yan, Juxiang Chen
Malignant gliomas are heterogeneous diseases in genetic basis. The development of sequencing techniques has identified many gene rearrangements encoding novel oncogenic fusions in malignant glioma to date. Understanding the gene fusions and how they regulate cellular processes in different subtypes of glioma will shed light on genomic diagnostic approaches for personalized treatment. By now, studies of gene fusions in glioma remain limited, and no medication has been approved for treating the malignancy harboring gene fusions...
March 20, 2018: Translational Oncology
Muxing Kang, Yaoyi Zhang, Xiaoli Jin, Guofeng Chen, Yi Huang, Dan Wu, Guogang Li, Jianzhen Shan, Pintong Huang, Jian Chen
The Notch signaling pathway has been identified as a therapeutic target for cancers. γ-Secretase inhibitors (GSIs) have been progressively recognized as potential anticancer drugs. The present study aimed to investigate the effects of anti-delta like legend 4 (anti-DLL4) treatment on the anticancer efficacy of GSIs in gastric cancer. SGC-7901-GFP human gastric cancer cells were tested for DLL4 expression by rosette formation test and immunofluorescence, and then were treated with anti-DLL4 antibody N-[N-(3,5-difluorophenacetyl)-L-ananyl]-S-phenylglycine t-butyl ester (DAPT, a type of GSI), or a combination of anti-DLL4 antibody and DAPT...
March 15, 2018: Translational Oncology
Mohammad Hadi Karbalaie Niya, Hossein Keyvani, Fahimeh Safarnezhad Tameshkel, Mostafa Salehi-Vaziri, Sedigheh Teaghinezhad-S, Farah Bokharaei Salim, Seyed Hamid Reza Monavari, Davod Javanmard
Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16-positive specimens were used for further analysis...
March 13, 2018: Translational Oncology
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