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https://www.readbyqxmd.com/read/29241186/strengthening-gastric-cancer-therapy-by-trastuzumab-conjugated-nanoparticles-with-simultaneous-encapsulation-of-anti-mir-21-and-5-fluorouridine
#1
Nan Hu, Jun Feng Yin, Ze Ji, Yidong Hong, Puyuan Wu, Baoxiang Bian, Ziyan Song, Rutian Li, Qin Liu, Fenglei Wu
BACKGROUND/AIMS: MicroRNA-21 is an oncogenic miR (oncomiR) frequently elevated in gastric cancer (GC). Overexpression of miR-21 decreases the sensitivity of GC cells to 5-fluorouridine (5-Fu) and trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2). Receptor-mediated endocytosis plays a crucial role in the delivery of biotherapeutics including anti-miRNA oligonucleotides (AMOs). This study is a continuation of earlier findings involving poly(ε-caprolactone) (PCL)-poly (ethylene glycol) (PEG) nanoparticles (PEG-PCL NPs), which were coated with trastuzumab to target GC with HER2 receptor over-expression using anti-miRNA-21 (AMO-21) and 5-Fu...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241071/insights-on-ornithine-decarboxylase-silencing-as-a-potential-strategy-for-targeting-retinoblastoma
#2
Sivashanmugam Muthukumaran, Renganathan Bhuvanasundar, Vetrivel Umashankar, K N Sulochana
Ornithine Decarboxylase (ODC) is a key enzyme involved in polyamine synthesis and is reported to be up regulated in several cancers. However, the effect of ODC gene silencing in retinoblastoma is to be understood for utilization in therapeutic applications. Hence, in this study, a novel siRNA (small interference RNA) targeting ODC was designed and validated in Human Y79 retinoblastoma cells for its effects on intracellular polyamine levels, Matrix Metalloproteinase 2 & 9 activity and Cell cycle. The designed siRNA showed efficient silencing of ODC mRNA expression and protein levels in Y79 cells...
December 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29240947/a-fth1-gene-pseudogene-microrna-network-regulates-tumorigenesis-in-prostate-cancer
#3
Jia Jia Chan, Zhi Hao Kwok, Xiao Hong Chew, Bin Zhang, Chao Liu, Tuck Wah Soong, Henry Yang, Yvonne Tay
Non-coding RNAs play a vital role in diverse cellular processes. Pseudogenes, which are non-coding homologs of protein-coding genes, were once considered non-functional evolutional relics. However, recent studies have shown that pseudogene transcripts can regulate their parental transcripts by sequestering shared microRNAs (miRNAs), thus acting as competing endogenous RNAs (ceRNAs). In this study, we utilize an unbiased screen to identify the ferritin heavy chain 1 (FTH1) transcript and multiple FTH1 pseudogenes as targets of several oncogenic miRNAs in prostate cancer (PCa)...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29240919/genome-wide-dose-dependent-inhibition-of-histone-deacetylases-studies-reveal-their-roles-in-enhancer-remodeling-and-suppression-of-oncogenic-super-enhancers
#4
Gilson J Sanchez, Phillip A Richmond, Eric N Bunker, Samuel S Karman, Joseph Azofeifa, Aaron T Garnett, Quanbin Xu, Graycen E Wheeler, Cathryn M Toomey, Qinghong Zhang, Robin D Dowell, Xuedong Liu
Histone deacetylase inhibitors (HDACIs) are known to alter gene expression by both up- and down-regulation of protein-coding genes in normal and cancer cells. However, the exact regulatory mechanisms of action remain uncharacterized. Here we investigated genome wide dose-dependent epigenetic and transcriptome changes in response to HDACI largazole in a transformed and a non-transformed cell line. Exposure to low nanomolar largazole concentrations (<GI50) predominantly resulted in upregulation of gene transcripts whereas higher largazole doses (≥GI50) triggered a general decrease in mRNA accumulation...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29240787/brd3-4-inhibition-and-flt3-ligand-deprivation-target-pathways-that-are-essential-for-the-survival-of-human-mll-af9-leukemic-cells
#5
Marco Carretta, Annet Z Brouwers-Vos, Matthieu Bosman, Sarah J Horton, Joost H A Martens, Edo Vellenga, Jan Jacob Schuringa
In the present work we aimed to identify targetable signaling networks in human MLL-AF9 leukemias. We show that MLL-AF9 cells critically depend on FLT3-ligand induced pathways as well as on BRD3/4 for their survival. We evaluated the in vitro and in vivo efficacy of the BRD3/4 inhibitor I-BET151 in various human MLL-AF9 (primary) models and patient samples and analyzed the transcriptome changes following treatment. To further understand the mode of action of BRD3/4 inhibition, we performed ChIP-seq experiments on the MLL-AF9 complex in THP1 cells and compared it to RNA-seq data of I-BET151 treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/29239811/the-wnt-%C3%AE-catenin-pathway-is-deregulated-in-cemento-ossifying-fibromas
#6
Thaís Dos Santos Fontes Pereira, Marina Gonçalves Diniz, Josiane Alves França, Rennan Garcias Moreira, Grazielle Helena Ferreira de Menezes, Sílvia Ferreira de Sousa, Wagner Henriques de Castro, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez
OBJECTIVE: The molecular pathogenesis of cemento ossifying fibroma (COF) is unclear. The purpose of this study was to investigate mutations in 50 oncogenes and tumor suppressor genes, including APC and CTNNB1, in which mutations in COF have been previously reported. In addition, we assessed the transcriptional levels of the Wnt/β-catenin pathway genes in COF. STUDY DESIGN: We used a quantitative polymerase chain reaction array to evaluate the transcriptional levels of 44 Wnt/β-catenin pathway genes in 6 COF samples, in comparison with 6 samples of healthy jaws...
November 24, 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/29239040/molecular-pathology-of-thyroid-tumours-of-follicular-cells-a-review-of-genetic-alterations-and-their-clinicopathological-relevance
#7
REVIEW
Giorgia Acquaviva, Michela Visani, Andrea Repaci, Kerry J Rhoden, Dario de Biase, Annalisa Pession, Tallini Giovanni
Thyroid cancer is the most common endocrine malignancy. Knowledge of the molecular pathology of thyroid tumours originating from follicular cells has greatly advanced in the past several years. Common molecular alterations, such as BRAF p.V600E, RAS point mutations, and fusion oncogenes (RET-PTC being the prototypical example), have been, respectively, associated with conventional papillary carcinoma, follicular-patterned tumours (follicular adenoma, follicular carcinoma, and the follicular variant of papillary carcinoma/non-invasive follicular thyroid neoplasm with papillary-like nuclear features), and with papillary carcinomas from young patients and arising after exposure to ionising radiation, respectively...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29239034/succinate-dehydrogenase-sdh-deficient-neoplasia
#8
REVIEW
Anthony J Gill
The succinate dehydrogenase (SDH) complex is a key respiratory enzyme composed of four subunits: SDHA, SDHB, SDHC and SDHD. Remarkably, immunohistochemistry for SDHB becomes negative whenever there is bi-alleic inactivation of any component of SDH, which is very rare in the absence of syndromic disease. Therefore, loss of SDHB immunohistochemistry serves as a marker of syndromic disease, usually germline mutation of one of the SDH subunits. Tumours which show loss of SDHB expression are termed succinate dehydrogenase-deficient...
January 2018: Histopathology
https://www.readbyqxmd.com/read/29238073/stage-dependent-therapeutic-efficacy-in-pi3k-mtor-driven-squamous-cell-carcinoma-of-the-skin
#9
Charbel Darido, Smitha R Georgy, Carleen Cullinane, Darren D Partridge, Rachael Walker, Seema Srivastava, Suraya Roslan, Marina R Carpinelli, Sebastian Dworkin, Richard B Pearson, Stephen M Jane
Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238070/the-interplay-between-mutant-p53-and-the-mevalonate-pathway
#10
REVIEW
Alejandro Parrales, Elizabeth Thoenen, Tomoo Iwakuma
Missense mutations in the TP53 gene lead to accumulation of dysfunctional TP53 proteins in tumors, showing oncogenic gain-of-function (GOF) activities. Stabilization of mutant TP53 (mutp53) is required for the GOF; however, the mechanisms by which mutp53 promotes cancer progression and how mutp53 stability is regulated are not completely understood. Recent work from our laboratory has identified statins, inhibitors of the mevalonate pathway, as degraders of conformational mutp53. Specific reduction of mevalonate-5-phosphate (MVP), a metabolic intermediate in the mevalonate pathway, by statins or mevalonate kinase (MVK) knockdown triggers CHIP ubiquitin ligase-mediated degradation of conformational mutp53 by inhibiting interaction between mutp53 and DNAJA1, a Hsp40 family member...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29238067/alternative-nhej-pathway-proteins-as-components-of-mycn-oncogenic-activity-in-human-neural-crest-stem-cell-differentiation-implications-for-neuroblastoma-initiation
#11
Erika A Newman, Sahiti Chukkapalli, Daniela Bashllari, Tina T Thomas, Raelene A Van Noord, Elizabeth R Lawlor, Mark J Hoenerhoff, Anthony W Opipari, Valerie P Opipari
Neuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29238047/negative-control-of-the-hgf-c-met-pathway-by-tgf-%C3%AE-a-new-look-at-the-regulation-of-stemness-in-glioblastoma
#12
Eleanna Papa, Michael Weller, Tobias Weiss, Elisa Ventura, Isabel Burghardt, Emese Szabó
Multiple target inhibition has gained considerable interest in combating drug resistance in glioblastoma, however, understanding the molecular mechanisms of crosstalk between signaling pathways and predicting responses of cancer cells to targeted interventions has remained challenging. Despite the significant role attributed to transforming growth factor (TGF)-β family and hepatocyte growth factor (HGF)/c-MET signaling in glioblastoma pathogenesis, their functional interactions have not been well characterized...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237911/functional-analysis-of-ret-with-multiple-endocrine-neoplasia-type-2
#13
Meihua Zhang, Yao Liu, Jie Fu, Ying Hu, Zheng Sun
BACKGROUND: Multiple endocrine neoplastic type 2 (MEN2) is an endocrine carcinoma syndrome which is caused by a germline activation mutation that occurs during transfection (RET) proto-oncogene transmission. MEN2A patients are affected by RET (C634Y, C634R) mutation; MEN2B patients are affected by RET (M918T) mutation. AIMS: We aim to identify RET mutations' (C634R and M918T) expression, location, and signaling activation during the disease's progression, which providing a theoretical basis for the study on etiology of multiple endocrine neoplasia...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29237705/cilia-loss-sensitizes-cells-to-transformation-by-activating-the-mevalonate-pathway
#14
Yue-Zhen Deng, Zhen Cai, Shuo Shi, Hao Jiang, Yu-Rong Shang, Ning Ma, Jing-Jing Wang, Dong-Xian Guan, Tian-Wei Chen, Ye-Fei Rong, Zhen-Yu Qian, Er-Bin Zhang, Dan Feng, Quan-Li Zhou, Yi-Nan Du, Dong-Ping Liu, Xing-Xu Huang, Lu-Ming Liu, Eugene Chin, Dang-Sheng Li, Xiao-Fan Wang, Xue-Li Zhang, Dong Xie
Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through β catenin-T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin-TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples...
December 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29237456/identification-of-potential-transcriptomic-markers-in-developing-pediatric-sepsis-a-weighted-gene-co-expression-network-analysis-and-a-case-control-validation-study
#15
Yiping Li, Yanhong Li, Zhenjiang Bai, Jian Pan, Jian Wang, Fang Fang
BACKGROUND: Sepsis represents a complex disease with the dysregulated inflammatory response and high mortality rate. The goal of this study was to identify potential transcriptomic markers in developing pediatric sepsis by a co-expression module analysis of the transcriptomic dataset. METHODS: Using the R software and Bioconductor packages, we performed a weighted gene co-expression network analysis to identify co-expression modules significantly associated with pediatric sepsis...
December 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29236311/mir-221-negatively-regulates-inflammation-and-insulin-sensitivity-in-white-adipose-tissue-by-repression-of-sirtuin-1-sirt1
#16
Jie Peng, Yuanfei Zhou, Zhao Deng, Hong Zhang, Yinghui Wu, Tongxing Song, Yang Yang, Hongkui Wei, Jian Peng
It is well known that obesity-induced white adipose tissue inflammation is an important reason for insulin-resistance and type 2 diabetes mellitus. Sirtuin-1 (SIRT1) is an important regulator of inflammtion response pathways in white adipose tissue. Here, we found that miR-221 negatively regulated SIRT1 in white adipose tissue during inflammation and HFD-induced obesity. MiR-221 is a putative oncogene which has been found overexpressed in a number of human tumors. Recently, it has also found that miR-221 was increased in obese adipose tissue and may be involved in inflammation and insulin-resistance...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236030/the-tumor-suppressor-p53-in-mucosal-melanoma-of-the-head-and-neck
#17
REVIEW
Marie Kristin Fritsche, Andreas Knopf
Despite worldwide prevention programs, the incidence for cutaneous melanoma is continuously increasing. Mucosal melanoma (MM) represents a rare but highly aggressive phenotype of common melanoma with predilection in the sinonasal system. Far away from ultraviolet sun exposure, the molecular mechanisms underlying tumorigenesis and the highly aggressive clinical behavior are poorly understood. In many solid malignomas of the head and neck region, p53 tumor suppressor functions as oncogene due to p53 protein stabilizing mutation...
December 13, 2017: Genes
https://www.readbyqxmd.com/read/29235923/oncogenic-braf-mutation-induces-dna-methylation-changes-in-a-murine-model-for-human-serrated-colorectal-neoplasia
#18
Catherine E Bond, Cheng Liu, Futoshi Kawamata, Diane M McKeone, Winnie Fernando, Saara Jamieson, Sally-Ann Pearson, Alexandra Kane, Susan L Woods, Tamsin R M Lannagan, Roshini Somashekar, Young Lee, Troy Dumenil, Gunter Hartel, Kevin J Spring, Jennifer Borowsky, Lochlan Fennell, Mark Bettington, Jason Lee, Daniel L Worthley, Barbara A Leggett, Vicki L J Whitehall
Colorectal cancer is a major cause of cancer death and approximately 20% arises within serrated polyps, which are under-recognized and poorly understood. Human serrated colorectal polyps frequently exhibit both oncogenic BRAF mutation and widespread DNA methylation changes, which are important in silencing genes restraining neoplastic progression. Here, we investigated whether in vivo induction of mutant Braf is sufficient to result in coordinated promoter methylation changes for multiple cancer-related genes...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29235476/breast-cancer-metastasis-suppressor-otud1-deubiquitinates-smad7
#19
Zhengkui Zhang, Yao Fan, Feng Xie, Hang Zhou, Ke Jin, Li Shao, Wenhao Shi, Pengfei Fang, Bing Yang, Hans van Dam, Peter Ten Dijke, Xiaofeng Zheng, Xiaohua Yan, Junling Jia, Min Zheng, Jin Jin, Chen Ding, Sheng Ye, Fangfang Zhou, Long Zhang
Metastasis is the main cause of death in cancer patients. TGF-β is pro-metastatic for malignant cancer cells. Here we report a loss-of-function screen in mice with metastasis as readout and identify OTUD1 as a metastasis-repressing factor. OTUD1-silenced cancer cells show mesenchymal and stem-cell-like characteristics. Further investigation reveals that OTUD1 directly deubiquitinates the TGF-β pathway inhibitor SMAD7 and prevents its degradation. Moreover, OTUD1 cleaves Lysine 33-linked poly-ubiquitin chains of SMAD7 Lysine 220, which exposes the SMAD7 PY motif, enabling SMURF2 binding and subsequent TβRI turnover at the cell surface...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29235475/structural-and-functional-dissection-of-the-dh-and-ph-domains-of-oncogenic-bcr-abl-tyrosine-kinase
#20
Sina Reckel, Charlotte Gehin, Delphine Tardivon, Sandrine Georgeon, Tim Kükenshöner, Frank Löhr, Akiko Koide, Lena Buchner, Alejandro Panjkovich, Aline Reynaud, Sara Pinho, Barbara Gerig, Dmitri Svergun, Florence Pojer, Peter Güntert, Volker Dötsch, Shohei Koide, Anne-Claude Gavin, Oliver Hantschel
The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution...
December 13, 2017: Nature Communications
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