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https://www.readbyqxmd.com/read/29158786/fh535-inhibits-proliferation-and-motility-of-colon-cancer-cells-by-targeting-wnt-%C3%AE-catenin-signaling-pathway
#1
Yanyan Chen, Xianping Rao, Kangmao Huang, Xiaoxia Jiang, Haohao Wang, Lisong Teng
Aberrant Wnt/β-catenin pathway activation is frequently observed in human colorectal cancer (CRC) and has become a promising target for CRC treatment. Our study aimed to evaluate the effect of FH535, a small molecule inhibitor of Wnt/β-catenin pathway, on two colon cancer cell lines, HT29 and SW480. We found FH535 significantly inhibited colon cancer cell proliferation in vitro and induced cell cycle arrest. Moreover, FH535 inhibited colon cancer xenograft growth in vivo. Wound-healing assay and Transwell assay revealed that FH535 notably suppressed migration and invasion of SW480 cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29158600/crispr-cas9-library-screening-for-drug-target-discovery
#2
REVIEW
Morito Kurata, Kouhei Yamamoto, Branden S Moriarity, Masanobu Kitagawa, David A Largaespada
CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signals. CRISPRa is highly useful in screening for gain of functions, and CRISPRi is a more powerful tool than RNA interference (RNAi) libraries in screening for loss of functions. Positive selection using a CRISPR library can detect survival cells with specific conditions, such as drug treatment, and it can easily clarify drug resistance mechanisms...
November 20, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29157442/a-deep-learning-based-multi-model-ensemble-method-for-cancer-prediction
#3
Yawen Xiao, Jun Wu, Zongli Lin, Xiaodong Zhao
BACKGROUND AND OBJECTIVE: Cancer is a complex worldwide health problem associated with high mortality. With the rapid development of the high-throughput sequencing technology and the application of various machine learning methods that have emerged in recent years, progress in cancer prediction has been increasingly made based on gene expression, providing insight into effective and accurate treatment decision making. Thus, developing machine learning methods, which can successfully distinguish cancer patients from healthy persons, is of great current interest...
January 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/29157215/integration-of-rna-seq-data-with-heterogeneous-microarray-data-for-breast-cancer-profiling
#4
Daniel Castillo, Juan Manuel Gálvez, Luis Javier Herrera, Belén San Román, Fernando Rojas, Ignacio Rojas
BACKGROUND: Nowadays, many public repositories containing large microarray gene expression datasets are available. However, the problem lies in the fact that microarray technology are less powerful and accurate than more recent Next Generation Sequencing technologies, such as RNA-Seq. In any case, information from microarrays is truthful and robust, thus it can be exploited through the integration of microarray data with RNA-Seq data. Additionally, information extraction and acquisition of large number of samples in RNA-Seq still entails very high costs in terms of time and computational resources...
November 21, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29156805/circulating-tumor-dna-shows-variable-clonal-response-of-breast-cancer-during-neoadjuvant-chemotherapy
#5
Ji-Yeon Kim, Donghyun Park, Dae-Soon Son, Seok Jin Nam, Seok Won Kim, Hae Hyun Jung, Yeon Jeong Kim, Gahee Park, Woong-Yang Park, Jeong Eon Lee, Yeon Hee Park
Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients. Serial plasma DNAs were collected at diagnosis, after the 1(st) cycle of NAC and after curative surgery...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156692/increased-transcriptional-and-metabolic-capacity-for-lipid-metabolism-in-the-peripheral-zone-of-the-prostate-may-underpin-its-increased-susceptibility-to-cancer
#6
Omar Al Kadhi, Maria H Traka, Antonietta Melchini, Perla Troncoso-Rey, Wiktor Jurkowski, Marianne Defernez, Purnima Pachori, Robert D Mills, Richard Y Ball, Richard F Mithen
The human prostate gland comprises three distinct anatomical glandular zones, namely the peripheral, central and transitional zones. Although prostate cancer can arise throughout the prostate, it is more frequent in the peripheral zone. In contrast, hyperplasia occurs most frequently in the transitional zone. In this paper, we test the hypothesis that peripheral and transitional zones have distinct metabolic adaptations that may underlie their different inherent predispositions to cancer and hyperplasia. In order to do this, we undertook RNA sequencing and high-throughput metabolic analyses of non-cancerous tissue from the peripheral and transitional zones of patients undergoing prostatectomy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156688/frequency-of-expression-and-generation-of-t-cell-responses-against-antigens-on-multiple-myeloma-cells-in-patients-included-in-the-gmmg-mm5-trial
#7
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
Background: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. Results: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156680/vemurafenib-resistance-via-de-novo-rbm-genes-mutations-and-chromosome-5-aberrations-is-overcome-by-combined-therapy-with-palbociclib-in-thyroid-carcinoma-with-braf-v600e
#8
Zeus A Antonello, Nancy Hsu, Manoj Bhasin, Giovanni Roti, Mukta Joshi, Paul Van Hummelen, Emily Ye, Agnes S Lo, S Ananth Karumanchi, Christine R Bryke, Carmelo Nucera
Purpose: Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAF(V600E) represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAF(WT/V600E)-positive PTC patient-derived cells with P16(-/-) (CDKN2A(-/-))...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153840/association-of-omics-features-with-histopathology-patterns-in-lung-adenocarcinoma
#9
Kun-Hsing Yu, Gerald J Berry, Daniel L Rubin, Christopher Ré, Russ B Altman, Michael Snyder
Adenocarcinoma accounts for more than 40% of lung malignancy, and microscopic pathology evaluation is indispensable for its diagnosis. However, how histopathology findings relate to molecular abnormalities remains largely unknown. Here, we obtained H&E-stained whole-slide histopathology images, pathology reports, RNA sequencing, and proteomics data of 538 lung adenocarcinoma patients from The Cancer Genome Atlas and used these to identify molecular pathways associated with histopathology patterns. We report cell-cycle regulation and nucleotide binding pathways underpinning tumor cell dedifferentiation, and we predicted histology grade using transcriptomics and proteomics signatures (area under curve >0...
November 13, 2017: Cell Systems
https://www.readbyqxmd.com/read/29153093/next-generation-sequencing-and-molecular-cytogenetic-characterization-of-etv6-lyn-fusion-due-to-chromosomes-1-8-and-12-rearrangement-in-acute-myeloid-leukemia
#10
Edmond S K Ma, Thomas S K Wan, Chun Hang Au, Dona N Ho, Shing Yan Ma, Margaret H L Ng, Tsun Leung Chan
In a newly diagnosed patient with acute myeloid leukemia (AML) and complex cytogenetics and negative for gene mutations associated with myeloid neoplasms, RNA sequencing by next-generation sequencing (NGS) through a large cancer-related gene panel showed ETV6-LYN leukemic fusion transcript. Breakpoint analysis of the NGS reads showed fusion of exon 5 of the ETV6 gene to exon 8 of the LYN gene. Metaphase fluorescence in situ hybridization (FISH) inferred a four-break rearrangement of three chromosomes, namely 1, 8 and 12...
December 2017: Cancer Genetics
https://www.readbyqxmd.com/read/29152119/a-genome-wide-comprehensively-analyses-of-long-noncoding-rna-profiling-and-metastasis-associated-lncrnas-in-renal-cell-carcinoma
#11
Xue Xu, Yongcan Xu, Chuanqin Shi, Baoyu Wang, Xiang Yu, Yanfen Zou, Tao Hu
Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151929/identification-of-circular-rna-signature-in-bladder-cancer
#12
Xiao Yang, Wenbo Yuan, Jun Tao, Peng Li, Chengdi Yang, Xiaheng Deng, Xiaolei Zhang, Jingyuan Tang, Jie Han, Jingzi Wang, Pengchao Li, Qiang Lu, Min Gu
Circular RNA (circRNA) comprises a class of endogenous species of RNA consisting of a circular loop that is crucial for genetic and epigenetic regulation. The significance of circRNA in bladder cancer (BCa) remains to be investigated. Here we performed genome‑wide circRNA analysis of 5 paired tumour and adjacent normal tissue samples from BCa patients via next generation sequencing (NGS) technology. Next we confirmed NGS data in a separate set of 32 paired BCa samples using quantitative real-time reverse transcription polymerase chain reaction...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151908/inhibition-of-prostate-cancer-cell-growth-in-vivo-with-short-hairpin-rna-targeting-satb1
#13
Qiang Wang, Shi-Cheng Hu, Chun-Sheng Yang, Jia-Cun Chen, Jun-Nian Zheng, Xiao-Qing Sun, Jun-Qi Wang
Despite previous advances, the treatment options for prostate cancer remain limited. For the purposes of gene knockdown, the utility of RNA interference has been demonstrated and is considered to have therapeutic potential. In the present study, a short hairpin RNA (shRNA) was used to assess the effect of special AT-rich sequence binding protein (SATB1) downregulation on the growth and metastatic potential of prostate cancer in xenograft nude mice. A plasmid carrying shRNA targeting SATB1, pSilencer-SATB1-shRNA, was successfully engineered...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29149911/the-analysis-of-novel-microrna-mimic-sequences-in-cancer-cells-reveals-lack-of-specificity-in-stem-loop-rt-qpcr-based-microrna-detection
#14
Patrick Winata, Marissa Williams, Eileen McGowan, Najah Nassif, Nico van Zandwijk, Glen Reid
OBJECTIVE: MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR...
November 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29149532/exploitation-of-micrornas-by-japanese-encephalitis-virus-in-human-microglial-cells
#15
Meghana Rastogi, Neha Srivastava, Sunit K Singh
JEV infection in CNS leads to the JE neuroinflammation. Children and old age individual have been reported to be more prone to JEV infection. MicroRNAs are endogenous, small non-coding RNAs, which regulate the gene expression. These are ∼22 nucleotide long, conserved RNA sequence that binds at the 3'UTR of a target mRNA and regulate the post-transcriptional gene expression. The role of microRNAs has been reported in several diseases like cancer, viral infection, neuro-degeneration, diabetes etc. In the present study, the human microglial cells were infected with JEV (JaOAr strain)...
November 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#16
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29149041/the-hmga1-pseudogene-7-induces-mir-483-and-mir-675-upregulation-by-activating-egr1-through-a-cerna-mechanism
#17
Marco De Martino, Giuseppe Palma, Amalia Azzariti, Claudio Arra, Alfredo Fusco, Francesco Esposito
Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA) sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#18
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147610/host-immune-response-index-in-gastric-cancer-identified-by-comprehensive-analyses-of-tumor-immunity
#19
Charny Park, Junhun Cho, Jeeyun Lee, So Young Kang, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Insuk Sohn, Sin Ho Jung, Myung-Soo Kang, Kyoung-Mee Kim
Tumor infiltrating lymphocytes (TIL) in Epstein-Barr virus (EBV)-associated/microsatellite-unstable (MSI) gastric carcinomas (GC) constitute immune-active principal cellular components of tumor microenvironment and contribute to better prognosis. With the remarkable success of cancer immunotherapies, there is an urgent need for a comprehensive understanding of tumor-immune interactions in patients with GC in the context of host immune response. To identify GC subtype-specific immune response gene set, we tested differentially expressed genes for MSI and EBV+ GC subtypes in randomly selected test set (n = 278) in merged ACRG-SMC microarray and TCGA RNA sequencing data set...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145975/in-cancer-a-to-i-rna-editing-can-be-the-driver-the-passenger-or-the-mechanic
#20
Nabeel S Ganem, Noa Ben-Asher, Ayelet T Lamm
In recent years, A-to-I RNA modifications performed by the Adenosine Deaminase Acting on RNA (ADAR) protein family were found to be expressed at altered levels in multiple human malignancies. A-to-I RNA editing changes adenosine to inosine on double stranded RNA, thereby changing transcript sequence and structure. Although A-to-I RNA editing have the potential to change essential mRNA transcripts, affecting their corresponding protein structures, most of the human editing sites identified to date reside in non-coding repetitive transcripts such as Alu elements...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
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