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Translational Oncology

Enrica Martinelli, Andrea Fattorossi, Alessandra Battaglia, Marco Petrillo, Giuseppina Raspaglio, Gian Franco Zannoni, Mara Fanelli, Daniela Gallo, Giovanni Scambia
Class III β-tubulin (TUBB3) overexpression in ovarian cancer (OC) associates with poor prognosis. We investigated whether TUBB3 overexpression elicited anti-TUBB3 antibody production in OC patients and whether these antibodies may have diagnostic and prognostic impact. The presence of serum anti-TUBB3 antibodies was investigated in 49 untreated OC patients and 44 healthy individuals by an in-house developed ELISA that used recombinant TUBB3 as the antigen. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of the assay...
February 12, 2018: Translational Oncology
Su Jin Lee, Jung Eun Kim, Seung Tae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Won Ki Kang, Young Suk Park, Ho Yeong Lim
BACKGROUND: Biliary tract cancers (BTCs) are known to have a dismal prognosis. A number of chemokines play important roles in the progress of BTCs. However, the serum levels of chemokines in BTCs have not yet been explored. METHODS: The sera of healthy donors (n = 8) and patients with BTCs who were enrolled in second line sunitinib trials (n = 27) were collected. The concentrations of three kinds of chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay...
February 12, 2018: Translational Oncology
Tao Zuo, Jinshuai Shan, Yang Liu, Rong Xie, Xiaochun Yu, Chen Wu
N-Acetylgalactosaminyltransferase-14 (GALNT14) is a member of acetylgalactosaminyltransferases family. We have shown that GALNT14 could promote breast cancer cell invasion. However, the underlying molecular mechanism is unclear. Here, using yeast two hybrid, we find that EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) interacts with GALNT14. Both in vitro and in vivo binding assays show that EFEMP2 is associated with GALNT14. Moreover, we find that GALNT14 mediates glycosylation of EFEMP2...
February 7, 2018: Translational Oncology
Fangzheng Wang, Chuner Jiang, Zhiming Ye, Quanquan Sun, Tongxin Liu, Min Xu, Peng Wu, Kaiyuan Shi, Bin Long, Zhenfu Fu, Yangming Jiang
OBJECTIVE: This study was conducted to assess the efficacy and safety of nimotuzumab combined with radiotherapy (RT) in elderly patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The clinical data of 75 nasopharyngeal carcinoma patients, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed from December 2008 to April 2014. They were aged 60 to 81 years (median 64 years). The distribution of disease was stage II in 10 (13...
February 6, 2018: Translational Oncology
Uwe Rudolf Max Reuter, Ralf Oettmeier, Uwe Hobohm
William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP) are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times...
February 6, 2018: Translational Oncology
Zhixian Liu, Mengyuan Li, Zehang Jiang, Xiaosheng Wang
Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features...
February 4, 2018: Translational Oncology
Qi Li, Wanfu Xie, Ning Wang, Chuankun Li, Maode Wang
Accumulating evidence indicates that cell division cycle 7-related protein kinase(CDC7) plays an essential role in tumor cells and it could induces cell proliferation and could be related to prognosis in multiple types of cancer. However, the biological role and molecular mechanism of CDC7 in GBM still remains unclear. In this study, we identified that CDC7 expression was enriched in glioblastoma (GBM) tumors and was functionally required for tumor proliferation and its expression was associated to poor prognosis in GBM patients...
February 4, 2018: Translational Oncology
Hans Jonas Meyer, Nikita Garnov, Alexey Surov
OBJECT: Nowadays, there is increasing evidence that functional magnetic resonance imaging (MRI) modalities, namely, diffusion-weighted imaging (DWI) and dynamic-contrast enhanced MRI (DCE MRI), can characterize tumor architecture like cellularity and vascularity. Previously, two formulas based on a logistic tumor growth model were proposed to predict tumor cellularity with DWI and DCE. The purpose of this study was to proof these formulas. METHODS: 16 patients with head and neck squamous cell carcinomas were included into the study...
February 2, 2018: Translational Oncology
Min He, Shanshan Liu, Sachith Gallolu Kankanamalage, Mark D Borromeo, Luc Girard, Adi F Gazdar, John D Minna, Jane E Johnson, Melanie H Cobb
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, designated as a recalcitrant cancer by the National Cancer Institute, in urgent need of new rational therapeutic targets. Previous studies have determined that the basic helix-loop-helix transcription factor achaete-scute homolog 1 (ASCL1) is essential for the survival and progression of a fraction of pulmonary neuroendocrine cancer cells, which include both SCLC and a subset of non-SCLC. Previously, to understand how ASCL1 initiates tumorigenesis in pulmonary neuroendocrine cancer and identify the transcriptional targets of ASCL1, whole-genome RNA-sequencing analysis combined with chromatin immunoprecipitation-sequencing was performed with a series of lung cancer cell lines...
February 1, 2018: Translational Oncology
Ting Jin, Feng Jiang, Qi-Feng Jin, Yong-Feng Piao, Xiao-Zhong Chen
OBJECTIVE: A previous phase-2 trial to assess the addition of Endostar to gemcitabine and cisplatin (GC) chemotherapy showed that it improves prognosis in metastatic nasopharyngeal carcinoma (M-NPC) but the study cohort was small. We wished to update that phase-2 trial by enrolling an additional 44 patients and to assess the benefit of Endostar+GC chemotherapy. METHODS: An analysis of 72 M-NPC patients treated between July 2010 and November 2016 was done. The treatment regimen was a combination of gemcitabine (1,000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and Endostar (15 mg/day) from day 1 to day 14 of a 21-day cycle for ≥2 cycles...
January 31, 2018: Translational Oncology
Jones Gyamfi, Minseob Eom, Ja-Seung Koo, Junjeong Choi
Breast cancer is the most common malignancy in women worldwide, with a developmental process spanning decades. The malignant cells recruit a variety of cells including fibroblasts, endothelial cells, immune cells, and adipocytes, creating the tumor microenvironment. The tumor microenvironment has emerged as active participants in breast cancer progression and response to treatment through autocrine and paracrine interaction with the malignant cells. Adipose tissue is abundant in the breast cancer microenvironment; interactions with cancer cells create cancer-associated adipocytes which produce a variety of adipokines that influence breast cancer initiation, metastasis, angiogenesis, and cachexia...
January 30, 2018: Translational Oncology
Anukriti Singh, Nidhi Srivastava, Sonal Amit, S N Prasad, M P Misra, Bushra Ateeq
Renin angiotensin system (RAS) comprising Angiotensin converting enzyme (ACE), Angiotensin II (Ang II) and its receptor Angiotensin II receptor type I (AGTR1), plays a critical role in several diseases including cancer. A single nucleotide polymorphism (SNP) A1166C located in 3' untranslated region (UTR) of AGTR1 and an insertion/deletion (I/D) polymorphism present in intron 16 of ACE gene have been associated with many diseases, but their association with Breast cancer (BCa) is still debatable. Here, we for the first time investigated the association of these polymorphisms in a North Indian BCa cohort including 161 patients and 152 healthy women...
January 30, 2018: Translational Oncology
Jeong Eun Kim, Deokhoon Kim, Yong Sang Hong, Kyu-Pyo Kim, Young Kwang Yoon, Dae Ho Lee, Sang-We Kim, Sung-Min Chun, Se Jin Jang, Tae Won Kim
Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR...
January 29, 2018: Translational Oncology
Sara Westrøm, Tina B Bønsdorff, Øyvind S Bruland, Roy H Larsen
BACKGROUND: Ovarian cancer patients with chemotherapy-resistant residual microscopic disease in the peritoneal cavity have a considerable need for new treatment options. Alpha-emitting radionuclides injected intraperitoneally may be an attractive therapeutic option in this situation as they are highly cytotoxic, while their short range in tissues can spare surrounding radiosensitive organs in the abdomen. Herein we evaluate the therapeutic efficacy of a novel α-emitting compound specifically designed for intracavitary radiation therapy...
January 27, 2018: Translational Oncology
Shengbin Shi, Quan Rao, Chuangnian Zhang, Xiuyuan Zhang, Yibo Qin, Zuoxing Niu
Advanced hepatocellular carcinoma (HCC) has limited therapeutic options. Immunotherapy is a promising treatment, while sorafenib is a first-line drug-based treatment for advanced HCC. However, the efficacy of sorafenib and immunotherapy in combination, have not been clearly evaluated. Sorafenib treatment has been shown to promote immunosuppression by increasing hypoxia in orthotopic HCC models. Here, we found that sorafenib treatment in mice with orthotopic HCC increased the expression of inhibitor programmed death-ligand 1 (PD-L1) and T-regulatory cells in tumor tissues...
January 27, 2018: Translational Oncology
Chao You, Anna K Kaiser, Pascal Baltzer, Julia Krammer, Yajia Gu, Weijun Peng, Stefan O Schönberg, Clemens G Kaiser
OBJECTIVE: To investigate promoting factors for background parenchymal enhancement (BPE) in MR mammography (MRM). METHODS: 146 patients were retrospectively evaluated, including 91 high-risk patients (50 BRCA patients, 41 patients with elevated lifetime risk). 56 screening patients were matched to the high-risk cases on the basis of age. The correlation of BPE with factors such as fibroglandular tissue (FGT), age, menopausal status, breast cancer, high-risk precondition as well as motion were investigated using linear regression...
January 27, 2018: Translational Oncology
Fangfang Fu, Weiqin Jiang, Linfu Zhou, Zhi Chen
Exosomes are extracellular membrane vesicles of 50- to 130-nm diameter secreted by most tumor cells. Exosomes can mediate the intercellular transfer of proteins and RNAs, including microRNAs (miRNAs), and promote both tumorigenesis and premetastatic niche formation. In this study, we performed exosomal RNA sequencing to identify candidate exosomal miRNAs that could be associated with colorectal cancer (CRC) and its distant metastasis. The expression profiles of exosomal miRNA, as secreted by isogenic human primary CRC cell line SW480 and highly metastatic cell line SW620, were analyzed and the potential targets related to tumorigenesis and metastatic progression were investigated...
January 20, 2018: Translational Oncology
Susanne Klein-Scory, Marina Maslova, Michael Pohl, Christina Eilert-Micus, Roland Schroers, Wolff Schmiegel, Alexander Baraniskin
PURPOSE: Despite therapeutic improvements, all patients with nonresectable metastatic colorectal cancer (mCRC) acquire resistance to treatment probably due to the growth of mutated clones. In contrast to tissue-based studies, liquid biopsies have enabled the opportunity to reveal emerging resistance to treatment by detecting mutated clones and noninvasively monitoring clonal dynamics during therapy. METHODS: The courses of three patients with mCRC who were initially RAS wild-type were monitored longitudinally using liquid biopsy with long-term follow-up of up to 20 sequential samples...
January 19, 2018: Translational Oncology
Tengfei Li, Ji Ma, Xinwei Han, Yongxu Jia, Huifeng Yuan, Shaofeng Shui, Dong Guo
Glioma is the most common cancer in human brain system and seriously threatens human health. miRNA-320 has been demonstrated to be closely correlated with the development of glioma. However, its effect and molecular mechanism underlying radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1) mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone formation assay, apoptosis assay, histone H2AX phosphorylation level (γH2AX) detection and caspase 3 activity analysis, respectively...
January 10, 2018: Translational Oncology
Mikael Montelius, Johan Spetz, Oscar Jalnefjord, Evelin Berger, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy response assessment, but associations between MR parameters, underlying biology, and therapeutic effects must be investigated. The aim of this study was to investigate response assessment efficacy and biological associations of MR parameters in a neuroendocrine tumor (NET) model subjected to radionuclide treatment. Twenty-one mice with NETs received 177Lu-octreotate at day 0. MR experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements (T1/T2*)...
January 10, 2018: Translational Oncology
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