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https://www.readbyqxmd.com/read/29779155/prioritising-risk-factors-for-type-2-diabetes-causal-inference-through-genetic-approaches
#1
REVIEW
Laura B L Wittemans, Luca A Lotta, Claudia Langenberg
PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown...
May 19, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29779034/ras-gtpase-activating-like-protein-iqgap1-iqgap1-promotes-breast-cancer-proliferation-and-invasion-and-correlates-with-poor-clinical-outcomes
#2
Fanye Zeng, Weihua Jiang, Wei Zhao, Yuxiang Fan, Yanhua Zhu, Hongliang Zhang
BACKGROUND Breast cancer is one of the most common female cancers in the world. As a key integrator of cell signaling pathways, IQGAP1 contributes to the development and progression of several cancers. However, the exact effects and molecular mechanisms of IQGAP1 in breast cancer progression remain poorly understood. MATERIAL AND METHODS In the present study, IQGAP1 expression was measured in 96 paired breast cancer samples and the corresponding adjacent non-cancerous tissues by immunohistochemistry and quantitative polymerase chain reaction...
May 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29779017/-xpg-rs17655-g-c-polymorphism-associated-with-cancer-risk-evidence-from-60-studies
#3
Jie Zhao, Shanshan Chen, Haixia Zhou, Ting Zhang, Yang Liu, Jing He, Jinhong Zhu, Jichen Ruan
Xeroderma pigmentosum group G (XPG), a key component in nucleotide excision repair pathway, functions to cut DNA lesions during DNA repair. Genetic variations that alter DNA repair gene expression or function may decrease DNA repair ability and impair genome integrity, thereby predisposing to cancer. The association between XPG rs17655 G>C polymorphism and cancer risk has been investigated extensively, but the results remain contradictory. To get a more accurate conclusion, we performed a comprehensive meta-analysis of 60 case-control studies, involving 27,098 cancer cases and 30,535 healthy controls...
May 20, 2018: Aging
https://www.readbyqxmd.com/read/29779016/integrated-analysis-of-colorectal-cancer-microrna-datasets-identification-of-micrornas-associated-with-tumor-development
#4
Luca Falzone, Letizia Scola, Antonino Zanghì, Antonio Biondi, Antonio Di Cataldo, Massimo Libra, Saverio Candido
Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets...
May 18, 2018: Aging
https://www.readbyqxmd.com/read/29778956/health-risk-assessment-of-heavy-metals-in-atmospheric-deposition-in-a-congested-city-environment-in-a-developing-country-kandy-city-sri-lanka
#5
Lakshika Weerasundara, D N Magana-Arachchi, Abdul M Ziyath, Ashantha Goonetilleke, Meththika Vithanage
This research study which was undertaken in a congested city environment in a developing country provides a robust approach for the assessment and management of human health risk associated with atmospheric heavy metals. The case study area was Kandy City, which is the second largest city in Sri Lanka and bears the characteristics of a typical city in the developing world such as the urban footprint, high population density and traffic congestion. Atmospheric deposition samples were collected on a weekly basis and analyzed for nine heavy metals common to urban environments, namely, Al, Cr, Mn, Fe, Ni, Cu, Zn, Cd and Pb...
May 17, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29778798/discovery-of-antitumor-ursolic-acid-long-chain-diamine-derivatives-as-potent-inhibitors-of-nf-%C3%AE%C2%BAb
#6
Wei Jiang, Ri-Zhen Huang, Jing Zhang, Tong Guo, Meng-Ting Zhang, Xiao-Chao Huang, Bin Zhang, Zhi-Xin Liao, Jing Sun, Heng-Shan Wang
A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC50 values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 5.22 to 8.95 μM...
May 8, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29778754/exosome-mediated-mir-222-transferring-an-insight-into-nf-%C3%AE%C2%BAb-mediated-breast-cancer-metastasis
#7
Jiaji Ding, Zhi Xu, Yanyan Zhang, Chunli Tan, Weizi Hu, Mei Wang, Yong Xu, Jinhai Tang
The subtypes of distant-organ metastasis led to treatment failure and poor prognosis are major obstacles in the management of patients with advanced breast cancer (BCa). Emerging evidences demonstrated that exosomes act as mediators for intercellular communication between various types of cells in the local tumor microenvironment. The present study aims to investigate whether BCa-derived exosomes are capable of cell-cell transferring miR-222 for BCa metastatic progression. Results showed that exosomal miR-222 is highly expressed in BCa patients with lymphatic metastasis...
May 17, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29778567/emp3-which-is-regulated-by-mir-663a-suppresses-gallbladder-cancer-progression-via-interference-with-the-mapk-erk-pathway
#8
Qiang Ma, Yijian Zhang, Haibin Liang, Fei Zhang, Fatao Liu, Shili Chen, Yunping Hu, Lin Jiang, Yajuan Hao, Maolan Li, Yingbin Liu
Gallbladder cancer (GBC) is the most common malignancy of the biliary tract and its molecular pathogenesis is poorly understood. Aberrant expression of epithelial membrane protein-3 (EMP3) was reported in different kinds of cancers. Our study aimed to explore the elusive functional roles and the underlying molecular mechanisms of EMP3 with respect to GBC progression. The results showed that human GBC tissues exhibited decreased levels of EMP3 compared with non-malignant tissues. Kaplan-Meier analysis indicated that low expression of EMP3 was associated with poor prognosis of GBC patients...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29778566/lung-squamous-cell-carcinoma-cells-express-non-canonically-glycosylated-igg-that-activates-integrin-fak-signaling
#9
Jingshu Tang, Jingxuan Zhang, Yang Liu, Qinyuan Liao, Jing Huang, Zihan Geng, Weiyan Xu, Zhengzuo Sheng, Gregory Lee, Youhui Zhang, Jinfeng Chen, Liang Zhang, Xiaoyan Qiu
It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH 1 domain...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29778422/sp1-induced-upregulation-of-lncrna-pandar-predicts-adverse-phenotypes-in-retinoblastoma-and-regulates-cell-growth-and-apoptosis-in-vitro-and-in-vivo
#10
Lijie Sheng, Jing Wu, Xuewu Gong, Duo Dong, Xiaoxue Sun
Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription...
May 17, 2018: Gene
https://www.readbyqxmd.com/read/29777993/toenail-selenium-genetic-variation-in-selenoenzymes-and-risk-and-outcome-in-glioma
#11
Noah C Peeri, Jordan H Creed, Gabriella M Anic, Reid C Thompson, Jeffrey J Olson, Renato V LaRocca, Sajeel A Chowdhary, John D Brockman, Travis A Gerke, L Burton Nabors, Kathleen M Egan
BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival...
May 16, 2018: Cancer Epidemiology
https://www.readbyqxmd.com/read/29777989/synthesis-antiproliferative-activity-and-mechanism-of-gallium-iii-thiosemicarbazone-complexes-as-potential-anti-breast-cancer-agents
#12
Jinxu Qi, Qian Yao, Kun Qian, Liang Tian, Zhen Cheng, Dongmei Yang, Yihong Wang
Five thiosemicarbazone ligands were synthesized and characterized by condensation with different aldehydes or ketones by 4-phenylthiosemicarbazone. The representative dichlorido[2-(Di-2-pyridinylmethylene)-Nphenylhydrazinecarbothioamide-N,N,S]-gallium(III) (Ga4) was characterized by X-ray single crystal diffraction, which was 1:1 ligand/Ga(III) complexes. The structure-activity relationship of these ligands and Ga (III) complexes have been investigated, and the results demonstrate that the formation of Ga (III) complexes have significant antiproliferative activity over the corresponding ligands...
May 14, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#13
Rahat Jahan, Muzafar A Macha, Satyanarayana Rachaghani, Srustidhar Das, Lynette M Smith, Sukhwinder Kaur, Surinder K Batra
Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest and polymorphic exon 2, along with exon 3...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777901/interrogation-of-ethnomedicinal-plants-for-synthetic-lethality-effects-in-combination-with-deficiency-in-the-dna-repair-endonuclease-rad1-using-a-yeast-cell-based-assay
#14
Hsu Mon Aung, Chananya Huangteerakul, Wittaya Panvongsa, Amornrat N Jensen, Arthit Chairoungdua, Suchada Sukrong, Laran T Jensen
ETHNOPHARMACOLOGICAL RELEVANCE: Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties. AIM OF THE STUDY: To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay...
May 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29777862/revealing-a-raf-functions-through-its-interactome
#15
Xin-Yu Zhang, Hui Guo, Bing Han, Xu-Min Zhang, Ying Huang, Yang Yang, Ying Liu, Xiao-Xi Guo, Qian Hao, Su An, Tian-RuiXu
A-Raf is a member of the Raf kinase family. Unlike B-Raf and C-Raf, the functions of A-Raf remain obscure. To gain more insight into the biological functions of A-Raf, we investigated the A-Raf interactome using proteomics. We found 132 proteins that interact with A-Raf and confirmed the interaction of 12 of these proteins with A-Raf by western blotting. Our data suggested that A-Raf regulates apoptosis, RNA catabolism, GTPase activity, and cell adhesion by interacting with proteins located in different cellular compartments...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777795/sirna-in-ovarian-cancer-delivery-strategies-and-targets-for-therapy
#16
REVIEW
Dirk van den Brand, Vicky Mertens, Leon F A G Massuger, Roland Brock
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the sixth leading cause of cancer related death in women overall. Despite improved surgical techniques and advances in chemotherapy, mortality hardly decreased over the last twenty years. The major problem is that (micro)metastases persevere in the abdominal cavity, causing incurable tumor recurrence. Therefore, there is an imminent need for new therapeutic strategies. Oligonucleotide (ON) based therapies such as RNA interference (RNAi) provide the possibility to specifically address disease-related pathways...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777792/human-cancer-cells-suppress-behaviors-of-endothelial-progenitor-cells-through-mir-21-targeting-il6r
#17
Wenbin Wang, Xiao Yuan, Aman Xu, Xingyang Zhu, Yanqing Zhan, Shuanhu Wang, Mulin Liu
Deep vein thrombosis (DVT) is a severe clinical process and has a high rate of fatality. Cancer patients have a high incidence rate of venous thrombosis complication and increase the mortality of cancer patients for 2-8 times. The mechanisms involved in human cancers and venous thrombosis remains unclear. In this study, we determined miR-21 expressed higher in human breast cancer, colon cancer and hepatocellular cancer tissues compared with normal tissues and expressed higher in exosomes of breast cancer and hepatocellular cancer cell lines compared with normal cells...
May 16, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29777784/cd146-mediates-an-e-cadherin-to-n-cadherin-switch-during-tgf-%C3%AE-signaling-induced-epithelial-mesenchymal-transition
#18
Yanbin Ma, Haofeng Zhang, Chaoliang Xiong, Zheng Liu, Qingji Xu, Jing Feng, Jun Zhang, Zhaoqing Wang, Xiyun Yan
Cadherin switch is an initiating factor of epithelial-mesenchymal transition (EMT) and is intimately correlated with cancer metastatic potential; however, its underlying mechanisms remain unclear. Here, using a transforming growth factor-β (TGF-β)-induced EMT model, we provide explicit evidence that CD146, with elevated expression and activity in a variety of cancers, is a key factor involved in the cadherin switch. We show that CD146 can be induced by TGF-β signaling. Moreover, CD146 expression is positively correlated with the activation levels of STAT3/Twist and ERK pathways...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777783/accelerated-lipid-catabolism-and-autophagy-are-cancer-survival-mechanisms-under-inhibited-glutaminolysis
#19
Anna Halama, Michal Kulinski, Shaima S Dib, Shaza B Zaghlool, Kodappully S Siveen, Ahmad Iskandarani, Jonas Zierer, Kirti S Prabhu, Noothan J Satheesh, Aditya M Bhagwat, Shahab Uddin, Gabi Kastenmüller, Olivier Elemento, Steven S Gross, Karsten Suhre
Suppressing glutaminolysis does not always induce cancer cell death in glutamine dependent tumors because cells may switch to alternative energy sources. To reveal compensatory metabolic pathways, we investigated the metabolome-wide cellular response to inhibited glutaminolysis in cancer cells. Glutaminolysis inhibition with C.968 suppressed cell proliferation but was insufficient to induce cancer cell death. We found that lipid catabolism was activated as a compensation for glutaminolysis inhibition. Accelerated lipid catabolism, together with oxidative stress induced by glutaminolysis inhibition, triggered autophagy...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777762/astrocyte-elevated-gene-1-is-a-novel-regulator-of-astrogliosis-and-excitatory-amino-acid-transporter-2-via-interplaying-with-nuclear-factor-%C3%AE%C2%BAb-signaling-in-astrocytes-from-amyotrophic-lateral-sclerosis-mouse-model-with-hsod1-g93a-mutation
#20
Xiang Yin, Shuyu Wang, Yan Qi, Xudong Wang, Hongquan Jiang, Tianhang Wang, Yueqing Yang, Ying Wang, Chunting Zhang, Honglin Feng
AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A -positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling...
May 16, 2018: Molecular and Cellular Neurosciences
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