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https://www.readbyqxmd.com/read/28427247/molecular-testing-of-lung-cancers
#1
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee
Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics...
April 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#2
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427239/foxo3a-dependent-bim-transcription-protects-mice-from-a-high-fat-diet-via-inhibition-of-activation-of-the-nlrp3-inflammasome-by-facilitating-autophagy-flux-in-kupffer-cells
#3
Liu Yan, Zhang Wenfeng, Wu Xiaoling, Gong Jianping
BACKGROUND: The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. RESULTS: Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3 inflammasome activation. Additionally, mRNA levels of Bim were significantly changed with the alteration of Foxo3a in KCs under PA and LPS stimulation among foxo3a targeted genes...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427228/mir-29a-regulated-er-positive-breast-cancer-cell-growth-and-invasion-and-is-involved-in-the-insulin-signaling-pathway
#4
Zhi-Hua Li, Qiu-Yun Xiong, Liang Xu, Peng Duan, Qianwen Ou Yang, Ping Zhou, Jian-Hong Tu
Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427210/dependence-of-p53-deficient-cells-on-the-dhx9-dexh-box-helicase
#5
Teresa Lee, Jerry Pelletier
DHX9 is a DExH-box helicase family member with key regulatory roles in a broad range of cellular processes. It participates at multiple levels of gene regulation, including DNA replication, transcription, translation, RNA transport, and microRNA processing. It has been implicated in tumorigenesis and recent evidence suggests that it may be a promising chemotherapeutic target. Previous studies have determined that DHX9 suppression elicits an apoptotic or senescence response by activating p53 signaling. Here, we show that DHX9 inhibition can also have deleterious effects in cells lacking functional p53...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427208/identification-of-differentially-expressed-lncrnas-involved-in-transient-regeneration-of-the-neonatal-c57bl-6j-mouse-heart-by-next-generation-high-throughput-rna-sequencing
#6
Yu-Mei Chen, Hua Li, Yi Fan, Qi-Jun Zhang, Xing Li, Li-Jie Wu, Zi-Jie Chen, Chun Zhu, Ling-Mei Qian
Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427202/clinical-implications-of-genomic-profiles-in-metastatic-breast-cancer-with-a-focus-on-tp53-and-pik3ca-the-most-frequently-mutated-genes
#7
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs. We evaluated somatic mutations from WES and targeted sequencing and assessed gene expression and performed pathway analysis from RNA-Seq. In this analysis, PIK3CA was the most commonly mutated gene in estrogen receptor (ER)-positive BC, while in ER-negative BC, TP53 was the most commonly mutated gene (p = 0...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427201/wnt5a-planar-cell-polarity-signaling-pathway-in-urothelial-carcinoma-a-potential-prognostic-biomarker
#8
Mark Saling, Jordan K Duckett, Ian Ackers, Karen Coschigano, Scott Jenkinson, Ramiro Malgor
Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427186/microrna-494-promotes-apoptosis-and-extracellular-matrix-degradation-in-degenerative-human-nucleus-pulposus-cells
#9
Liang Kang, Cao Yang, Yu Song, Kangcheng Zhao, Wei Liu, Wenbin Hua, Kun Wang, Ji Tu, Shuai Li, Huipeng Yin, Yukun Zhang
PURPOSE: This study investigated the expression and function of the microRNA-494 in intervertebral disc degeneration (IDD). RESULTS: MicroRNA-494 expression was upregulated during IDD progression; its overexpression increased the expression of ECM catabolic factors such as matrix metalloproteinase and A disintegrin and metalloproteinase with thrombospondin motif in NP cells while decreasing that of anabolic genes such as type II collagen and aggrecan; it also induced the apoptosis of NP cells, as determined by flow cytometry...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427184/kpnb1-mediated-nuclear-import-is-required-for-motility-and-inflammatory-transcription-factor-activity-in-cervical-cancer-cells
#10
Tamara Stelma, Virna D Leaner
Karyopherin β1 is a nuclear import protein involved in the transport of proteins containing a nuclear localisation sequence. Elevated Karyopherin β1 expression has been reported in cancer and transformed cells and is essential for cancer cell proliferation and survival. Transcription factors such as NFĸB and AP-1 contain a nuclear localisation sequence and initiate the expression of multiple factors associated with inflammation and cancer cell biology. Our study investigated the effect of inhibiting nuclear import via Karyopherin β1 on cancer cell motility and inflammatory signaling using siRNA and the novel small molecule, Inhibitor of Nuclear Import-43, INI-43...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427183/random-walk-based-method-to-identify-prognostic-genes-in-colorectal-cancer
#11
Xue Yang, Chen Zhao, Ning An
Currently, colorectal cancer remains one of the major causes of cancer mortality worldwide, despite significant advances in understanding its molecular mechanism. It has been putatively accepted that CRC, in most case, is a highly complicated process through adenoma-carcinoma sequence. Therefore, thorough researches regarding the molecular abnormalities, especially in precancerous stage, might be helpful in discovering potential biomarkers and promising therapeutic targets. Moreover, differentially expressed genes consistently dysregulated throughout the whole carcinogenic process might substantially reduce potential noise created by large-scale tumor heterogeneity...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427182/identification-of-dbccr1-as-a-suppressor-in-the-development-of-lung-cancer-that-is-associated-with-increased-dna-methyltransferase-1
#12
Guoren Zhou, Jinjun Ye, Ying Fang, Zhi Zhang, Jingyuan Zhang, Lei Sun, Jifeng Feng
Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427158/the-varied-distribution-and-impact-of-ras-codon-and-other-key-dna-alterations-across-the-translocation-cyclin-d-subgroups-in-multiple-myeloma
#13
Caleb K Stein, Charlotte Pawlyn, Shweta Chavan, Leo Rasche, Niels Weinhold, Adam Corken, Amy Buros, Pieter Sonneveld, Graham H Jackson, Ola Landgren, Tariq Mughal, Jie He, Bart Barlogie, P Leif Bergsagel, Faith E Davies, Brian A Walker, Gareth J Morgan
We examined a set of 805 cases that underwent DNA sequencing using the FoundationOne Heme (F1H) targeted sequencing panel and gene expression profiling. Known and likely variant calls from the mutational data were analyzed for significant associations with gene expression defined translocation cyclin D (TC) molecular subgroups. The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427151/fine-tuning-of-vitamin-d-receptor-vdr-activity-by-post-transcriptional-and-post-translational-modifications
#14
REVIEW
Ondrej Zenata, Radim Vrzal
Vitamin D receptor (VDR) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcription factors. Activated VDR is responsible for maintaining calcium and phosphate homeostasis, and is required for proper cellular growth, cell differentiation and apoptosis. The expression of both phases I and II drug-metabolizing enzymes is also regulated by VDR, therefore it is clinically important.Post-translational modifications of NRs have been known as an important mechanism modulating the activity of NRs and their ability to drive the expression of target genes...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427132/-influences-of-abar-gene-on-biofilm-formation-of-acinetobacter-baumannii
#15
H N Guo, J Xiang
Objective: To detect drug-resistant phenotype and abaR gene of Acinetobacter baumannii (AB) and investigate influences of abaR gene on biofilm formation of AB. Methods: From February to July 2014, 159 strains AB were collected from Department of Clinical Microbiology of Ruijin Hospital of School of Medicine of Shanghai JiaoTong University and numbered starting from 1 according time when they were collected. (1) The above-mentioned 159 strains of AB were identified by detecting gene sequence of 16S ribosomal DNA...
April 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28427045/mir-142-3p-overexpression-increases-chemo-sensitivity-of-nsclc-by-inhibiting-hmgb1-mediated-autophagy
#16
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. METHODS: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo...
March 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28426952/plant-viruses-and-bacteriophages-for-delivery-in-medicine-and-biotechnology
#17
REVIEW
Anna E Czapar, Nicole F Steinmetz
There are a wide variety of synthetic and naturally occurring nanomaterials under development for nanoscale cargo-delivery applications. Viruses play a special role in these developments, because they can be regarded as naturally occurring nanomaterials evolved to package and deliver cargos. While any nanomaterial has its advantage and disadvantages, viral nanoparticles (VNPs), in particular the ones derived from plant viruses and bacteriophages, are attractive options for cargo-delivery as they are biocompatible, biodegradable, and non-infectious to mammals...
April 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28426816/ex-vivo-cultures-combined-with-vivo-morpholino-induced-gene-knockdown-provide-a-system-to-assess-the-role-of-wt1-and-gata4-during-gonad-differentiation
#18
Lucas J Rudigier, Christof Dame, Holger Scholz, Karin M Kirschner
Gonad morphogenesis relies on the correct spatiotemporal expression of a number of genes that together fulfill the differentiation of the bipotential gonad into testes or ovaries. As such, the transcription factors WT1 and GATA4 are pivotal for proper gonadal development. Here we address the contributions of GATA4 and WT1 to the sex differentiation phase in testes and ovaries. We applied an ex vivo technique for cultivating gonads in hanging droplets of media that were supplemented with vivo-morpholinos to knockdown WT1 and GATA4 either alone or in combination at the same developmental stage...
2017: PloS One
https://www.readbyqxmd.com/read/28426805/evidence-of-horizontal-gene-transfer-by-transposase-gene-analyses-in-fervidobacterium-species
#19
Alba Cuecas, Wirojne Kanoksilapatham, Juan M Gonzalez
Horizontal Gene Transfer (HGT) plays an important role in the physiology and evolution of microorganisms above all thermophilic prokaryotes. Some members of the Phylum Thermotogae (i.e., Thermotoga spp.) have been reported to present genomes constituted by a mosaic of genes from a variety of origins. This study presents a novel approach to search on the potential plasticity of Fervidobacterium genomes using putative transposase-encoding genes as the target of analysis. Transposases are key proteins involved in genomic DNA rearrangements...
2017: PloS One
https://www.readbyqxmd.com/read/28426790/lethality-of-mice-bearing-a-knockout-of-the-ngly1-gene-is-partially-rescued-by-the-additional-deletion-of-the-engase-gene
#20
Haruhiko Fujihira, Yuki Masahara-Negishi, Masaru Tamura, Chengcheng Huang, Yoichiro Harada, Shigeharu Wakana, Daisuke Takakura, Nana Kawasaki, Naoyuki Taniguchi, Gen Kondoh, Tadashi Yamashita, Yoko Funakoshi, Tadashi Suzuki
The cytoplasmic peptide:N-glycanase (Ngly1 in mammals) is a de-N-glycosylating enzyme that is highly conserved among eukaryotes. It was recently reported that subjects harboring mutations in the NGLY1 gene exhibited severe systemic symptoms (NGLY1-deficiency). While the enzyme obviously has a critical role in mammals, its precise function remains unclear. In this study, we analyzed Ngly1-deficient mice and found that they are embryonic lethal in C57BL/6 background. Surprisingly, the additional deletion of the gene encoding endo-β-N-acetylglucosaminidase (Engase), which is another de-N-glycosylating enzyme but leaves a single GlcNAc at glycosylated Asn residues, resulted in the partial rescue of the lethality of the Ngly1-deficient mice...
April 2017: PLoS Genetics
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