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Molecular Oncology

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https://www.readbyqxmd.com/read/28941026/transcription-instability-in-high-risk-neuroblastoma-is-associated-with-a-global-perturbation-of-chromatin-domains
#1
Carlo Zanon, Gian Paolo Tonini
Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN) we first devised a metric we named TIN-index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN-index values compared to low-intermediate risk (LIR) patients...
September 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28922552/an-individualized-gene-expression-signature-for-prediction-of-lung-adenocarcinoma-metastases
#2
Lishuang Qi, Tianhao Li, Gengen Shi, Jiasheng Wang, Xin Li, Sainan Zhang, Libin Chen, Yuan Qin, Yunyan Gu, Wenyuan Zhao, Zheng Guo
Our laboratory previously reported an individual-level signature consisting of nine gene pairs, named 9-GPS. This signature was developed by training on microarray expression data and validated using three independent integrated microarray data sets, with samples of stage I non-small cell lung cancer after complete surgical resection. In this study, we first validated the cross-platform robustness of 9-GPS by demonstrating that 9-GPS could significantly stratify the overall survival of 213 stage I lung adenocarcinoma (LUAD) patients detected with RNA-sequencing platform in The Cancer Genome Atlas (log-rank p = 0...
September 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28922540/ape1-ref-1-knockdown-in-pancreatic-ductal-adenocarcinoma-characterizing-gene-expression-changes-and-identifying-novel-pathways-using-single-cell-rna-sequencing
#3
Fenil Shah, Emery Goossens, Nadia M Atallah, Michelle Grimard, Mark R Kelley, Melissa L Fishel
Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1 knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single-cell RNA Sequencing to identify differentially expressed genes in relation to APE1 protein levels within the cell...
September 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28881081/a-genetically-inducible-porcine-model-of-intestinal-cancer
#4
Morten Møbjerg Callesen, Sigrid Salling Árnadóttir, Iben Lyskjaer, Mai-Britt Worm Ørntoft, Søren Høyer, Frederik Dagnaes-Hansen, Ying Liu, Rong Li, Henrik Callesen, Mads Heilskov Rasmussen, Martin Fogtmann Berthelsen, Martin Kristian Thomsen, Pawel Jan Schweiger, Kim Bak Jensen, Søren Laurberg, Torben Falck Ørntoft, Jannik Ejnar Elverløv-Jakobsen, Claus Lindbjerg Andersen
Transgenic porcine cancer models bring novel possibilities for research. Their physical similarities with humans enable the use of surgical procedures and treatment approaches used for patients, which facilitates clinical translation. Here, we aimed to develop an inducible oncopig model of intestinal cancer. Transgenic (TG) minipigs were generated using somatic cell nuclear transfer by hand-made cloning. The pigs encode two TG cassettes: 1) An Flp-recombinase inducible oncogene cassette containing KRAS-G12D, cMYC, SV40LT - which inhibits p53 - and pRB...
September 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28865178/inhibition-of-il-6-jak-stat3-signaling-in-castration-resistant-prostate-cancer-cells-enhances-the-nk-cell-mediated-cytotoxicity-via-alteration-of-pd-l1-nkg2d-ligand-levels
#5
LiJun Xu, XiaoDong Chen, MingJing Shen, Dong-Rong Yang, Laifu Fang, Guobin Weng, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
To investigate whether IL-6 signaling affects the susceptibility of castration resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL-6 level) were developed by lentiviral transduction. While observing no secreted IL-6 level in parental C4-2 and CWR22Rv1 cells, we found the IL-6 expression/secretion in these cells was induced after the transduction process and the IL-6 level difference in C4-2siIL-6/sc and CWR22siIL-6/sc cell CRPC cell sets could be detected...
September 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28853212/tissue-glycomics-distinguish-tumour-sites-in-women-with-advanced-serous-adenocarcinoma
#6
Merrina Anugraham, Francis Jacob, Arun Vijay Everest-Dass, Andreas Schoetzau, Sheri Nixdorf, Neville F Hacker, Daniel Fink, Viola Heinzelmann-Schwarz, Nicolle H Packer
In the era of precision medicine, the tailoring of cancer treatment is increasingly important as we transition from organ-based diagnosis towards a more comprehensive and patient-centric molecular diagnosis. This is particularly the case for high-grade serous adenocarcinomas of the ovary and peritoneum, which are commonly diagnosed at an advanced stage, and collectively treated and managed similarly. We characterized the N- and O- glycome of serous ovarian (OC) and peritoneal cancer (PC) tissues using PGC-LC-ESI-IT-MS/MS profiling and validated the discriminatory glycans and their corresponding glyco-gene expression levels using cell lines and transcriptomic data from 232 patients...
August 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28846832/induction-of-a-novel-isoform-of-the-lncrna-hotair-in-claudin-low-breast-cancer-cells-attached-to-extracellular-matrix
#7
Miao Li, Xi Li, Yan Zhuang, Erik K Flemington, Lin Zhen, Bin Shan
Elevated overexpression of the lncRNA HOTAIR mediates invasion and metastasis in breast cancer. In an apparent paradox, we observed low expression of HOTAIR in the invasive Claudin-low MDA-MB-231 and Hs578T cells in two-dimensional culture (2D). However, HOTAIR expression exhibited robust induction in laminin-rich extracellular matrix based three-dimensional organotypic culture (lrECM 3D) over that in 2D culture. Induction of HOTAIR required intact ECM signaling, namely integrin α2 and SRC kinase activity...
August 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28846829/rhogdi%C3%AE-promotes-sp1-mmp-2-expression-and-bladder-cancer-invasion-through-perturbing-mir-200c-targeted-jnk2-protein-translation
#8
Haishan Huang, Honglei Jin, Huirong Zhao, Jingjing Wang, Xin Li, Huiying Yan, Shuai Wang, Xirui Guo, Lei Xue, Jingxia Li, Minggang Peng, Annette Wang, Junlan Zhu, Xue-Ru Wu, Changyan Chen, Chuanshu Huang
Our most recent studies demonstrate that RhoGDIβ is able to promote human bladder cancer (BC) invasion and metastasis in an X-link inhibitor of apoptosis protein-dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)-2 protein expression. We also found that RhoGDIβ and MMP-2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIβ inhibited MMP-2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIβ upregulated MMP-2 protein expression and promoted invasion as well...
August 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28815885/novel-landscape-of-hla-g-isoforms-expressed-in-clear-cell-renal-cell-carcinoma-patients
#9
Diana Tronik-Le Roux, Julie Renard, Jérôme Vérine, Victor Renault, Emmanuel Tubacher, Joel LeMaoult, Nathalie Rouas-Freiss, Jean-François Deleuze, François Desgrandschamps, Edgardo D Carosella
Immune-checkpoints are powerful inhibitory molecules that promote tumor survival. Their blockade is now recognized as providing effective therapeutic benefit against cancer. HLA-G, a recently identified immune checkpoint, has been detected in many types of primary tumors and metastases, in malignant effusions as well as on tumor-infiltrating cells, particularly in patients with clear cell renal cell carcinoma (ccRCC). Here, in order to define a possible anti-cancer therapy, we used a molecular approach based on an unbiased strategy that combines transcriptome determination and immunohistochemical labeling, to analyze in-depth, the HLA-G isoforms expressed in these tumors...
August 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28796930/recurrence-associated-gene-signature-optimizes-recurrence-free-survival-prediction-of-colorectal-cancer
#10
Xianglong Tian, Xiaoqiang Zhu, Tingting Yan, Chenyang Yu, Chaoqin Shen, Ye Hu, Jie Hong, Haoyan Chen, Jing-Yuan Fang
High throughput gene expression profiling has showed great promise in providing insight into molecular mechanisms. Metastasis-related mRNAs may potentially enrich genes with the ability to predict cancer recurrence,therefore we attempted to build a recurrence-associated gene signature to improve prognostic prediction of colorectal cancer (CRC). We identified 2848 differentially expressed mRNAs by analyzing CRC tissues with or without metastasis. For the selection of prognostic genes, a LASSO Cox regression model was employed...
August 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28783244/loss-of-ampk-activation-promotes-the-invasion-and-metastasis-of-pancreatic-cancer-through-an-hsf1-dependent-pathway
#11
Ke Chen, Weikun Qian, Jie Li, Zhengdong Jiang, Liang Cheng, Bin Yan, Junyu Cao, Liankang Sun, Cancan Zhou, Meng Lei, Wanxing Duan, Jiguang Ma, Qingyong Ma, Zhenhua Ma
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a mortality rate that closely parallels its incidence rate, and a better understanding of the molecular and cellular mechanisms associated with the invasion and distant metastasis is required. Heat shock factor 1 (HSF1) is a very highly conserved factor in eukaryotes that regulates the protective heat shock response. Here, we show that HSF1 is abnormally activated in pancreatic cancer. The knockdown of HSF1 impaired the invasion and migration and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells in vitro; however, the upregulation of HSF1 showed the opposite effects...
August 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28766847/expression-of-insulin-like-growth-factor-1-receptor-in-circulating-tumor-cells-of-patients-with-breast-cancer-is-associated-with-patient-outcomes
#12
Maria Spiliotaki, Dimitris Mavroudis, Maria Kokotsaki, Eleni-Kyriaki Vetsika, Ioannis Stoupis, Alexios Matikas, Galatea Kallergi, Vassilis Georgoulias, Sofia Agelaki
In patients with breast cancer, markers of aggressiveness such as dysregulation of the insulin-like growth factor receptor (IGF1R) system and E-cadherin loss are commonly observed. Reduced IGF1R expression is correlated with decreased E-cadherin levels and increased cell motility. We assessed IGF1R and E-cadherin expression in circulating tumor cells (CTCs) in breast cancer patients. Peripheral blood mononuclear cells of early (n=87) and metastatic (n=126) stage breast cancer patients (obtained prior to adjuvant and first-line chemotherapy) were evaluated using double immunofluorescence (IF) staining for cytokeratin (CK) and IGF1R...
August 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28755527/targeted-dianthin-is-a-powerful-toxin-to-treat-pancreatic-carcinoma-when-applied-in-combination-with-the-glycosylated-triterpene-so1861
#13
Cheenu Bhargava, Horst Dürkop, Xiangli Zhao, Alexander Weng, Matthias F Melzig, Hendrik Fuchs
Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma, however, a number of protein-based targeted toxins lack efficacy due to insufficient endosomal escape after being endocytosed. Therefore, we tested a fusion protein of the ribosome-inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer. In vitro investigations with the pancreatic carcinoma cell lines BxPC-3 and MIA PaCa-2 revealed no significant differences to off-target cells in the half maximal inhibitory concentration (IC50 ) for the fusion protein...
July 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28741788/molecular-analysis-of-single-circulating-tumour-cells-following-long-term-storage-of-clinical-samples
#14
Barbara Mesquita, Dominic G Rothwell, Deborah J Burt, Francesca Chemi, Fabiola Fernandez-Gutierrez, Daniel Slane-Tan, Jenny Antonello, Mathew Carter, Louise Carter, Marina Parry, Lynsey Franklin, Richard Marais, Fiona Blackhall, Caroline Dive, Ged Brady
The CellSearch® semi-automated CTC enrichment and staining system has been established as the "gold standard" for CTC enumeration with CellSearch® CTC counts recognized by the FDA as prognostic for a number of cancers. We and others have gone on to show that molecular analysis of CellSearch® CTCs isolated shortly after CellSearch® enrichment provides another valuable layer of information that has potential clinical utility including predicting response to treatment. Although CellSearch® CTCs can be readily isolated after enrichment, the process of analysing a single CellSearch® patient sample, which may contain many CTCs, is both time consuming and costly...
July 25, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28719033/identification-of-driver-copy-number-alterations-in-diverse-cancer-types-and-application-in-drug-repositioning
#15
Wenbin Zhou, Zhangxiang Zhao, Ruiping Wang, Yue Han, Chengyu Wang, Fan Yang, Ya Han, Haihai Liang, Lishuang Qi, Chenguang Wang, Zheng Guo, Yunyan Gu
Results from numerous studies suggest an important role for somatic copy number alterations (SCNAs) in cancer progression. Our work aimed to identify the drivers (oncogenes or tumor suppressor genes) that reside in recurrently aberrant genomic regions, including a large number of genes or non-coding genes, which remain a challenge for decoding the SCNAs involved in carcinogenesis. Here, we propose a new approach to comprehensively identify drivers, using 8740 cancer samples involving 18 cancer types from The Cancer Genome Atlas (TCGA)...
July 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28700115/lkb1-pro-oncogenic-activity-triggers-cell-survival-in-circulating-tumor-cells
#16
Elisabeth Katharina Trapp, Leonie Majunke, Beate Zill, Harald Sommer, Ulrich Andergassen, Julian Koch, Nadia Harbeck, Sven Mahner, Thomas Wolfram Paul Friedl, Wolfgang Janni, Brigitte Rack, Marianna Alunni-Fabbroni
During intravasation, circulating tumor cells (CTCs) detach from the epithelium of origin and begin the Epithelial-to Mesenchymal-Transition (EMT) process, where they lose epithelial features and pass through the endothelium to enter circulation. Although detachment from the extracellular matrix is a strong source of metabolic stress, which induces anoikis, CTCs can survive. Recently, the tumor suppressor liver kinase B1 (LKB1) has gained attention for its role as a proto-oncogene in restoring the correct ATP/AMP ratio during metabolic stress...
July 12, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28691390/an-improved-digital-polymerase-chain-reaction-protocol-to-capture-low-copy-kras-mutations-in-plasma-cell-free-dna-by-resolving-subsampling-issues
#17
Yusuke Ono, Ayumu Sugitani, Hidenori Karasaki, Munehiko Ogata, Reo Nozaki, Junpei Sasajima, Tomoki Yokochi, Shingo Asahara, Kazuya Koizumi, Kiyohiro Ando, Katsunori Hironaka, Tsutomu Daito, Yusuke Mizukami
Genetic alterations responsible for the initiation of cancer may serve as immediate biomarkers for early diagnosis. Plasma levels of cell-free DNA (cfDNA) in patients with cancer are higher than those in healthy individuals; however, the major technical challenge for the widespread implementation of cfDNA genotyping as a diagnostic tool is the insufficient sensitivity and specificity of detecting early-stage tumors that shed low amounts of cfDNA. To establish a protocol for ultrasensitive droplet digital polymerase chain reaction (ddPCR) for quantification of low-frequency alleles within a limited cfDNA pool, two-step multiplex ddPCR targeting eight clinically relevant mutant KRAS variants was examined...
July 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28675785/gas6-expressing-and-self-sustaining-cancer-cells-in-3d-spheroids-activate-the-pdk-rsk-mtor-pathway-for-survival-and-drug-resistance
#18
Christine Baumann, Axel Ullrich, Robert Torka
AXL receptor tyrosine kinase (RTK) inhibition presents a promising therapeutic strategy for aggressive tumor subtypes, as AXL signaling is upregulated in many cancers resistant to first-line treatments. Furthermore, the AXL ligand growth arrest-specific gene 6 (GAS6) has recently been linked to cancer drug resistance. Here, we established that challenging conditions, such as serum deprivation, divide AXL-overexpressing tumor cell lines into non-self-sustaining and self-sustaining subtypes in 3D spheroid culture...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28675654/bioinformatory-assisted-analysis-of-next-generation-sequencing-data-for-precision-medicine-in-pancreatic-cancer
#19
Linnéa Malgerud, Johan Lindberg, Valtteri Wirta, Maria Gustafsson-Liljefors, Masoud Karimi, Carlos Fernández Moro, Katrin Stecker, Alexander Picker, Carolin Huelsewig, Martin Stein, Regina Bohnert, Marco Del Chiaro, Stephan L Haas, Rainer L Heuchel, Johan Permert, Markus J Maeurer, Stephan Brock, Caroline S Verbeke, Lars Engstrand, David B Jackson, Henrik Grönberg, Johannes- Matthias Löhr
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity...
July 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28672103/shingosine-1-phosphate-suppresses-chondrosarcoma-metastasis-by-up-regulation-of-tissue-inhibitor-of-metalloproteinase-3-through-suppressing-mir-101-expression
#20
Chun-Hao Tsai, Dong-Ying Yang, Chih-Yang Lin, Tsung-Ming Chen, Chih-Hsin Tang, Yuan-Li Huang
Chondrosarcoma is the second most common primary malignancy form of bone cancer, exhibiting resistance to chemotherapy and radiation therapy as well as developing high metastasis ability in late stage tumors. Thus, understanding the metastatic processes of chondrosarcoma is considered a strategy for treatment of this disease. Sphingosine 1-phosphate (S1P), a bioactive sphingolipid, is produced intracellularly by sphingosine kinase (SphK) and is regarded as a second signaling molecule that regulates inflammation, proliferation, angiogenesis, and metastasis...
July 3, 2017: Molecular Oncology
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