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Translational Oncology

Jeong Hwan Park, Cheol Lee, Mee Soo Chang, Kwangsoo Kim, Seongmin Choi, Hyunjung Lee, Hyun-Seob Lee, Kyung Chul Moon
Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...
June 17, 2018: Translational Oncology
Georg Alexander Gihr, Diana Horvath-Rizea, Patricia Kohlhof-Meinecke, Oliver Ganslandt, Hans Henkes, Cindy Richter, Karl-Titus Hoffmann, Alexey Surov, Stefan Schob
BACKGROUND: Meningiomas are the most frequently diagnosed intracranial masses, oftentimes requiring surgery. Especially procedure-related morbidity can be substantial, particularly in elderly patients. Hence, reliable imaging modalities enabling pretherapeutic prediction of tumor grade, growth kinetic, realistic prognosis, and-as a consequence-necessity of surgery are of great value. In this context, a promising diagnostic approach is advanced analysis of magnetic resonance imaging data...
June 14, 2018: Translational Oncology
Giuseppe Bronte, Sara Bravaccini, Sara Ravaioli, Maurizio Puccetti, Emanuela Scarpi, Daniele Andreis, Maria Maddalena Tumedei, Samanta Sarti, Lorenzo Cecconetto, Elisabetta Pietri, Valeria De Simone, Roberta Maltoni, Massimiliano Bonafè, Dino Amadori, Andrea Rocca
Genomic studies have shown that the androgen receptor (AR) pathway plays an important role in some breast cancer subtypes. However few data are present on the concordance between AR expression in primary tumors and metastases. We investigated AR expression by using immunohistochemistry (IHC) in 164 primary tumors and 83 metastases, to explore its distribution in the different tumor subtypes and its concordance between the two sample types and according to sampling time. AR was more highly expressed in luminal A and B than HER2-positive and triple negative primary tumors...
June 8, 2018: Translational Oncology
Tracy L Luks, Tracy Richmond McKnight, Llewellyn E Jalbert, Aurelia Williams, Evan Neill, Khadjia A Lobo, Anders I Persson, Arie Perry, Joanna J Phillips, Annette M Molinaro, Susan M Chang, Sarah J Nelson
The goal of this research was to elucidate the relationship between WHO 2016 molecular classifications of newly diagnosed, nonenhancing lower grade gliomas (LrGG), tissue sample histopathology, and magnetic resonance (MR) parameters derived from diffusion, perfusion, and 1 H spectroscopic imaging from the tissue sample locations and the entire tumor. A total of 135 patients were scanned prior to initial surgery, with tumor cellularity scores obtained from 88 image-guided tissue samples. MR parameters were obtained from corresponding sample locations, and histograms of normalized MR parameters within the T2 fluid-attenuated inversion recovery lesion were analyzed in order to evaluate differences between subgroups...
June 5, 2018: Translational Oncology
Crystal Tonnessen-Murray, Nathan A Ungerleider, Sonia G Rao, Amanda R Wasylishen, Wesley D Frey, James G Jackson
p53 is a transcription factor that regulates expression of genes involved in cell cycle arrest, senescence, and apoptosis. TP53 harbors mutations that inactivate its transcriptional activity in roughly 30% of breast cancers, and these tumors are much more likely to undergo a pathological complete response to chemotherapy. Thus, the gene expression program activated by wild-type p53 contributes to a poor response. We used an in vivo genetic model system to comprehensively define the p53- and p21-dependent genes and pathways modulated in tumors following doxorubicin treatment...
May 28, 2018: Translational Oncology
Nazia Riaz, Romana Idress, Sadia Habib, Iqbal Azam, El-Nasir Ma Lalani
BACKGROUND: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival. PATIENTS AND METHODS: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with clinicopathological variables and outcome using univariable and multivariable analysis...
May 26, 2018: Translational Oncology
Sushil Kumar, Jessica D Sun, Libo Zhang, Reza Bayat Mokhtari, Bing Wu, Fanying Meng, Qian Liu, Deepthi Bhupathi, Yan Wang, Herman Yeger, Charles Hart, Sylvain Baruchel
Antiangiogenic therapy has shown promising results in preclinical and clinical trials. However, tumor cells acquire resistance to this therapy by gaining ability to survive and proliferate under hypoxia induced by antiangiogenic therapy. Combining antiangiogenic therapy with hypoxia-activated prodrugs can overcome this limitation. Here, we have tested the combination of antiangiogenic drug sunitinib in combination with hypoxia-activated prodrug evofosfamide in neuroblastoma. In vitro, neuroblastoma cell line SK-N-BE(2) was 40-folds sensitive to evofosfamide under hypoxia compared to normoxia...
May 23, 2018: Translational Oncology
Rui Wang, Qilin Fan, Junjie Zhang, Xunan Zhang, Yuqi Kang, Zhirong Wang
Mannosyl (alpha-1,6-)-Glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5) is exclusively expressed in gastric carcinoma, and plays an essential role in cancer progression, but no targeted drug is available so far. The potential anti-cancer effect of Hydrogen Sulfide (H2 S), has not been widely recognized. It intrigued broad interest to explore the clinical benefits of cancer therapy, with the current understanding of molecular mechanisms of H2 S which remains very limited. In this study, we identify that H2 S is an effective inhibitor of MGAT5, leading to reduce the expression of exclusively abnormal glycoprotein processes in gastric carcinoma...
May 22, 2018: Translational Oncology
Xiang Li, Xu Lan, Grace Wang, Yi Liu, Ke Zhao, Shan-Zheng Lu, Xiao-Xi Xu, Gang-Gang Shi, Kui Ye, Bao-Ren Zhang, Yi-Ming Zhao, Hong-Qiu Han, Cai-Gan Du, Thomas E Ichim, Hao Wang
INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b ) donors to BALB/c (H-2d ) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time...
May 21, 2018: Translational Oncology
Qixin Leng, Yue Wang, Feng Jiang
Cell-free microRNAs in plasma provide circulating biomarkers for lung cancer. Most techniques for analysis of miRNAs require a large plasma volume to purify a sufficient RNA yield followed by complicated downstream processing. Small differences in the multiple procedures often cause large analytical variations and poor diagnostic values of the plasma biomarkers. Here we investigate whether directly quantifying plasma miRNAs without RNA purification could diagnose lung cancer. FirePlex assay was directly applied to 20 μl plasma of 56 lung cancer patients and 28 cancer free controls for quantifying 11 lung tumor-associated miRNAs...
May 17, 2018: Translational Oncology
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
Martyna Krzykawska-Serda, Jason Chak-Shing Ho, Matthew J Ware, Justin J Law, Jared M Newton, Lam Nguyen, Mahdi Agha, Steven A Curley, Stuart J Corr
Noninvasive radiofrequency-induced (RF) hyperthermia has been shown to increase the perfusion of chemotherapeutics and nanomaterials through cancer tissue in ectopic and orthotopic murine tumor models. Additionally, mild hyperthermia (37°C-45°C) has previously shown a synergistic anticancer effect when used with standard-of-care chemotherapeutics such as gemcitabine and Abraxane. However, RF hyperthermia treatment schedules remain unoptimized, and the mechanisms of action of hyperthermia and how they change when treating various tumor phenotypes are poorly understood...
May 11, 2018: Translational Oncology
Yonghuan Mao, Ling Xi, Quan Li, Sheng Wang, Zeling Cai, Xinhua Zhang, Chunzhao Yu
The prognosis of pancreatic cancer (PC) remains pessimistic because of the difficulty in early diagnosis as well as the little advance in chemotherapy. Although being the first-line chemotherapy drug for PC at present, gemcitabine still has some disadvantages, such as low drug sensitivity and significant side effects. Thus, how to further improve the sensitivity of PC cells to gemcitabine is still a difficult subject in the field of pancreatic cancer-treatment. Polo-like kinase 1 (Plk1) is closely related to poor outcome in many malignant tumors and its high expression is linked to chemoresistance in PC...
May 9, 2018: Translational Oncology
Wenxiang Zhi, Yu Wang, Cai Chang, Fen Wang, Yaling Chen, Na Hu, Xiaoli Zhu, Li Xie
PURPOSE: To investigate breast cancers total hemoglobin concentration (THC) characteristics and its association with clinical pathologic findings. MATERIALS AND METHODS: The study was approved by the institutional review board and all patients provided written informed consent. 447 breast cancer patients, totally 455 lesions were included in our study. The size and THC of breast lesions were measured by conventional ultrasound (US) and US-guided Diffuse Optical Tomography (DOT) 1-2 days before surgery...
May 9, 2018: Translational Oncology
Jae-Yong Nam, Bo Young Oh, Hye Kyung Hong, Joon Seol Bae, Tae Won Kim, Sang Yun Ha, Donghyun Park, Woo Yong Lee, Hee Cheol Kim, Seong Hyeon Yun, Yoon Ah Park, Je-Gun Joung, Woong-Yang Park, Yong Beom Cho
BACKGROUND: Signet-ring cell carcinoma (SRCC) is a very rare subtype of colorectal adenocarcinoma (COAD) with a poor clinical prognosis. Although understanding key mechanisms of tumor progression in SRCCs is critical for precise treatment, a comprehensive view of genomic alterations is lacking. MATERIALS AND METHODS: We performed whole-exome sequencing of tumors and matched normal blood as well as RNA sequencing of tumors and matched normal colonic tissues from five patients with SRCC...
May 7, 2018: Translational Oncology
Ivana Catacchio, Anna Scattone, Nicola Silvestris, Anita Mangia
Lung cancer is the leading cause of cancer deaths throughout the world. The majority of patients are diagnosed with locally advanced or metastatic disease when surgery, the best curative option, is no longer feasible. Thus, the prognosis of lung cancer remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of tumor microenvironment, with regard to the immune component, may provide valuable information for a better comprehension of the pathogenesis and progression of the disease...
May 2, 2018: Translational Oncology
Anthony J Cesnik, Bing Yang, Andrew Truong, Tyler Etheridge, Michele Spiniello, Maisie I Steinbrink, Michael R Shortreed, Brian L Frey, David F Jarrard, Lloyd M Smith
INTRODUCTION: The molecular mechanisms underlying aggressive versus indolent disease are not fully understood. Recent research has implicated a class of molecules known as long noncoding RNAs (lncRNAs) in tumorigenesis and progression of cancer. Our objective was to discover lncRNAs that differentiate aggressive and indolent prostate cancers. METHODS: We analyzed paired tumor and normal tissues from six aggressive Gleason score (GS) 8-10 and six indolent GS 6 prostate cancers...
April 30, 2018: Translational Oncology
Chen Shen, Zhenyu Liu, Zhaoqi Wang, Jia Guo, Hongkai Zhang, Yingshu Wang, Jianjun Qin, Hailiang Li, Mengjie Fang, Zhenchao Tang, Yin Li, Jinrong Qu, Jie Tian
PURPOSE: To build and validate a radiomics-based nomogram for the prediction of pre-operation lymph node (LN) metastasis in esophageal cancer. PATIENTS AND METHODS: A total of 197 esophageal cancer patients were enrolled in this study, and their LN metastases have been pathologically confirmed. The data were collected from January 2016 to May 2016; patients in the first three months were set in the training cohort, and patients in April 2016 were set in the validation cohort...
June 2018: Translational Oncology
Eunsung Jun, Juyun Oh, Song Lee, Hye-Ryeong Jun, Eun Hye Seo, Jin-Young Jang, Song Cheol Kim
Nucleic acid sequencing is frequently used to determine the molecular basis of diseases. Therefore, proper storage of biological specimens is essential to inhibit nucleic acid degradation. RNA isolated from the human pancreas is generally of poor quality because of its high concentration of endogenous RNase. In this study, we optimized the method for extracting high quality RNA from paired tumor and normal pancreatic tissues obtained from eight pancreatic cancer patients post-surgery. RNA integrity number (RIN) was checked to evaluate the integrity of RNA, we tried to extract the RNA with an RIN value of 8 or higher that allows for the latest genetic analysis...
June 2018: Translational Oncology
M G Torras, E Canals, D Jurado-Bruggeman, S Marín-Borras, M Macià, J Jové, A M Boladeras, C Muñoz-Montplet, J Molero, C Picón, M Puigdemont, L Aliste, A Torrents, F Guedea, J M Borras
BACKGROUND: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. METHODS: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings...
June 2018: Translational Oncology
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