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https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#1
REVIEW
Brett Fleisher, Kayla Andrews, Ashley A Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28734729/mir-143-regulates-the-proliferation-and-migration-of-osteosarcoma-cells-through-targeting-mapk7
#2
Xiancheng Dong, Bin Lv, Wei Liu, Qinghua Cheng, Chuan Su, Guoyong Yin
Accumulating documents have been suggested that microRNA-143 (miR-143) function as a tumor suppressor, involved in many biological processes including tumor initiation and progression. However, the biological function and molecular mechanism of miR-143 in Osteosarcoma (OS) still remains to be further investigated. Despite many efforts have been made, the prognosis of OS is still unsatisfied. Thus, exploring the underlying mechanism of OS and finding new treatment targets is essential for improving the survival rate of OS patients...
July 19, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28732379/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#3
Anan Yin, Amandine Etcheverry, Yalong He, Marc Aubry, Jill Barnholtz-Sloan, Luhua Zhang, Xinggang Mao, Weijun Chen, Bolin Liu, Wei Zhang, Jean Mosser, Xiang Zhang
Molecular and clinical heterogeneity critically hinders better treatment outcome for glioblastomas (GBMs); integrative analysis of genomic and epigenomic data may provide useful information for improving personalized medicine. By applying training-validation approach, we identified a novel hypomethylation signature comprising of three CpGs at non-CpG island (CGI) open sea regions for GBMs. The hypomethylation signature consistently predicted poor prognosis of GBMs in a series of discovery and validation datasets...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729954/clinical-streptococcal-isolates-distinct-from-streptococcus-pneumoniae-but-containing-the-%C3%AE-glucosyltransferase-tts-gene-and-expressing-serotype-37-capsular-polysaccharide
#4
Carmen L Sheppard, Georgia Kapatai, Karen Broughton, Ulf Schaefer, Matthew Hannah, David J Litt, Norman K Fry
The major virulence factor of the pneumococcus, and target for conjugate vaccines, is the polysaccharide capsule, which is usually encoded by the highly variable cps locus. Serotype 37 is an unusual pneumococcal type in which the single β-glucosyltransferase gene responsible for serotype capsule production (tts) is located outside of the capsular operon region. Using a previously described automated whole genome sequence (WGS)-based serotyping bioinformatics tool, PneumoCaT, we identified and investigated seven clinical isolates (three from blood cultures) of non-pneumococcal streptococci containing a highly homologous tts and included them in a study panel of 20 isolates which included a 11 further clinical isolates of S...
2017: PeerJ
https://www.readbyqxmd.com/read/28727425/the-database-and-bioinformatics-studies-of-probiotics
#5
Lin Tao, Bohua Wang, Yafen Zhong, Siok Hoon Pow, Xian Zeng, Chu Qin, Peng Zhang, Shangying Chen, Weidong He, Ying Tan, Hongxia Liu, Yuyang Jiang, Weiping Chen, Yu Zong Chen
Probiotics have been widely explored for health benefits, animal cares, and agricultural applications. Recent advances in microbiome, microbiota and microbial dark matter research have fueled greater interests in and paved ways for the study of the mechanisms of probiotics and the discovery of new probiotics from uncharacterized microbial sources. A probiotics database named PROBIO was developed to facilitate these efforts and the need for the information of the known probiotics, which provides the comprehensive information about the probiotic functions of 448 marketed, 167 clinical trial/field trial and 382 research probiotics for use or being studied for use in humans, animals, and plants...
July 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28725241/mir-378-suppresses-the-proliferation-migration-and-invasion-of-colon-cancer-cells-by-inhibiting-sdad1
#6
Mingxi Zeng, Linlin Zhu, Liangping Li, Changming Kang
BACKGROUND: MicroRNAs (miRNAs) play important roles in the growth and metastasis of colon cancer. It is known that one set of miRNAs are dysregulated in colon cancer cells, but the mechanism of their role in cancer development is still largely unknown. Our study focuses on the role of miR-378 in colon cancer cells. METHODS: Human colon cancer tissues and adjacent non-tumor tissues were collected from patients diagnosed in pathological examinations. In addition, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and a normal colonic mucosa cell line NCM460 were included...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28717660/a-novel-molecular-diagnostics-platform-for-somatic-and-germline-precision-oncology
#7
Rubén Cabanillas, Marta Diñeiro, David Castillo, Patricia C Pruneda, Cristina Penas, Guadalupe A Cifuentes, Álvaro de Vicente, Noelia S Durán, Rebeca Álvarez, Gonzalo R Ordóñez, Juan Cadiñanos
BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28717185/clinical-significance-and-effect-of-lncrna-hoxa11-as-in-nsclc-a-study-based-on-bioinformatics-in-vitro-and-in-vivo-verification
#8
Yu Zhang, Wen-Jie Chen, Ting-Qing Gan, Xiu-Ling Zhang, Zu-Cheng Xie, Zhi-Hua Ye, Yun Deng, Ze-Feng Wang, Kai-Teng Cai, Shi-Kang Li, Dian-Zhong Luo, Gang Chen
HOXA11 antisense RNA (HOXA11-AS) has been shown to be involved in tumorigenesis and development of different cancers. However, the role of HOXA11-AS in non-small cell lung cancer (NSCLC) remains unclear. In this study, we firstly explored and confirmed the expression of HOXA11-AS in NSCLC tissues and cells. Cytometry, CCK-8, cell scratch, migration, Matrigel invasion and flow cytometry assays were performed to determine the biological impact of HOXA11-AS in vitro. Furthermore, a chick embryo chorioallantoic membrane (CAM) model of NSCLC was constructed to explore the effect of HOXA11-AS on tumorigenicity and angiogenesis in vivo...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716860/novel-mechanisms-of-piezo1-dysfunction-in-hereditary-xerocytosis
#9
Edyta Glogowska, Eve R Schneider, Yelena Maksimova, Vincent P Schulz, Kimberly Lezon-Geyda, John Wu, Kottayam Radhakrishnan, Siobán B Keel, Donald Mahoney, Alison M Freidmann, Rachel A Altura, Elena O Gracheva, Sviatoslav N Bagriantsev, Theodosia A Kalfa, Patrick G Gallagher
Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We utilized next generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected HX and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore region domain. Several mutations were novel and demonstrated ethnic specificity. We characterized these mutations using genomic, bioinformatic, cell biology, and physiology-based functional assays...
July 17, 2017: Blood
https://www.readbyqxmd.com/read/28716001/variant-ranker-a-web-tool-to-rank-genomic-data-according-to-functional-significance
#10
John Alexander, Dimitris Mantzaris, Marianthi Georgitsi, Petros Drineas, Peristera Paschou
BACKGROUND: The increasing volume and complexity of high-throughput genomic data make analysis and prioritization of variants difficult for researchers with limited bioinformatics skills. Variant Ranker allows researchers to rank identified variants and determine the most confident variants for experimental validation. RESULTS: We describe Variant Ranker, a user-friendly simple web-based tool for ranking, filtering and annotation of coding and non-coding variants...
July 17, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28714515/elncrna1-a-long-non-coding-rna-that-is-transcriptionally-induced-by-oestrogen-promotes-epithelial-ovarian-cancer-cell-proliferation
#11
Jun-Jun Qiu, Xiao-Dan Zhang, Xiao-Yan Tang, Ting-Ting Zheng, Ying Zhang, Ke-Qin Hua
Previously, the novel oestrogen (E2)-upregulated lncRNA TC0101441, was identified by us, via microarray analysis. However, the detailed mechanism by which E2 upregulates TC0101441 and the role of TC0101441 in epithelial ovarian cancer (EOC) progression have not been elucidated. In the present study, we further analysed TC0101441, which we designated oestrogen-induced long non-coding RNA-1 (ElncRNA1). We showed that E2 transcriptionally upregulates ElncRNA1 through the oestrogen receptor α (ERα)-oestrogen response element (ERE) pathway using RNA stability assays, bioinformatics-based searches for ERE binding sites, chromatin immunoprecipitation (ChIP) assays and dual luciferase reporter assays...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28714009/microrna-202-inhibits-cell-proliferation-migration-and-invasion-of-glioma-by-directly-targeting-metadherin
#12
Jinsheng Yang, Bo Fan, Yachao Zhao, Junchao Fang
Glioma is the most common and aggressive type of primary malignant brain tumour. Increasing evidence has revealed that microRNAs play important roles in multiple biological processes related to glioma occurrence, development, diagnosis, treatment and prognosis. MicroRNA-202 (miR-202) has been studied in several types of human cancer, whereas the biological roles of miR-202 in glioma remain unknown. The present study, aimed to investigate the expression, clinical significance and biological roles of miR-202 in glioma, as well as its underlying molecular mechanism...
July 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28714005/microrna%C3%A2-455-is-downregulated-in-gastric-cancer-and-inhibits-cell-proliferation-migration-and-invasion-via-targeting-insulin%C3%A2-like-growth-factor-1-receptor
#13
Shan Zhang, Wan-Ling Yin, Xin Zhang, Xiao-Yu Zhang
Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA‑455 (miR‑455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR‑455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713950/microrna%C3%A2-302a-suppresses-cell-proliferation-migration-and-invasion-in-osteosarcoma-by-targeting-adam9
#14
Xiaoming Yang, Yan Cui, Fuqiang Yang, Chao Sun, Xuejian Gao
Osteosarcoma (OS) is the most frequent malignant primary bone tumor arising from primitive bone‑forming mesenchymal cells in children and adolescents. The dysregulation of microRNAs (miRNAs) has been reported in OS, and these aberrantly expressed miRNAs are involved in the initiation and progression of OS. The aim of the present study was to investigate the expression and functions of miRNA‑302a (miR‑302a) in OS and its underlying mechanism. It was found that the expression of miR‑302a was reduced in OS tissues and cell lines...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712006/an-inframe-trinucleotide-deletion-in-mtrr-exon-1-is-associated-with-the-risk-of-spina-bifida
#15
Jun Zhang, Xiao-Lu Dai, Gui-Cen Liu, Juan Wang, Xue-Yi Ren, Mu-Hua Jin, Nan-Nan Mi, Shu-Qin Wang
Maternal genetic variants of enzymes in folate-homocysteine metabolic network are significantly correlative with the risk of spina bifida. To survey the genetic causality, the genotypes of three women having spina bifida fetuses from two unrelated Chinese families were screened in candidate alleles. Polymerase chain reaction, capillary electrophoresis and Sanger sequencing were employed to recognize the allelic variation. A trinucleotide deletion (c.4_6delAGG) was identified in the first exon of MTRR. All the three women showed the novel clinical variation including one heterozygous and two homozygous...
July 15, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28709933/identification-of-novel-biomarker-and-therapeutic-target-candidates-for-diagnosis-and-treatment-of-follicular-carcinoma
#16
Xianyin Lai, Christopher B Umbricht, Kurt Fisher, Justin Bishop, Qiuying Shi, Shaoxiong Chen
Distinguishing follicular carcinoma from follicular adenoma, based on cytomorphological features, has always been challenging to cytopathologists. Identification of biomarkers for improving diagnostic accuracy is important for clinical management. Meanwhile, it is critical to identify therapeutic target candidates for treatment of follicular carcinoma. Currently, no reliable diagnostic protein biomarkers and therapeutic targets are available. To explore novel protein biomarker and therapeutic target candidates, a liquid chromatography-tandem mass spectrometry approach was applied to analyze control, follicular adenoma, and follicular carcinoma using formalin-fixed, paraffin-embedded tissue samples...
July 11, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28705755/isolation-and-whole-genome-sequence-analysis-of-the-imipenem-heteroresistant-acinetobacter-baumannii-clinical-isolate-hrab-85
#17
Puyuan Li, Yong Huang, Lan Yu, Yannan Liu, Wenkai Niu, Dayang Zou, Huiying Liu, Jing Zheng, Xiuyun Yin, Jing Yuan, Xin Yuan, Changqing Bai
OBJECTIVES: Heteroresistance is a phenomenon in which there are various responses to antibiotics from bacterial cells within the same population. Here, we isolated and characterised an imipenem heteroresistant Acinetobacter baumannii strain (HRAB-85). METHODS: The genome of strain HRAB-85 was completely sequenced and analysed to understand its antibiotic resistance mechanisms. POPULATION: analysis and multilocus sequence typing were performed...
July 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28705115/microrna-21-versus-microrna-34-lung-cancer-promoting-and-inhibitory-micrornas-analysed-in-silico-and-in-vitro-and-their-clinical-impact
#18
Meik Kunz, Claudia Göttlich, Thorsten Walles, Sarah Nietzer, Gudrun Dandekar, Thomas Dandekar
MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28704799/microrna-539-inhibits-glioma-cell-proliferation-and-invasion-by-targeting-dixdc1
#19
Junjie Quan, Jianqiang Qu, Le Zhou
Dysregulation of microRNAs (miRNAs) has been suggested to contribute to malignant progression of glioma. Previous studies have demonstrated that miR-539 is dysregulated in malignant progression of cancers. However, the potential role and mechanism of miR-539 in the progression of glioma remains unclear. In this study, we aimed to investigate the expression status and functional significance of miR-539 in glioma. We found that miR-539 expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-539 markedly inhibited glioma cell proliferation and invasion, while miR-539 suppression exhibited the opposite effect...
July 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28700537/qst-response-patterns-to-capsaicin-and-uv-b-induced-local-skin-hypersensitization-in-healthy-subjects-a-machine-learned-analysis
#20
Jörn Lötsch, Gerd Geisslinger, Sarah Heinemann, Florian Lerch, Bruno G Oertel, Alfred Ultsch
The comprehensive assessment of pain-related human phenotypes requires combinations of nociceptive measures that produce complex high-dimensional data, posing challenges to bioinformatic analysis. In this study, we assessed established experimental models of heat hyperalgesia of the skin, consisting of local ultraviolet-B (UV-B) irradiation or capsaicin application, in 82 healthy subjects using a variety of noxious stimuli. We extended the original heat simulation by applying cold and mechanical stimuli and assessing the hypersensitization effects with a clinically established quantitative sensory testing (QST) battery (German Research Network on Neuropathic Pain)...
July 8, 2017: Pain
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