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https://www.readbyqxmd.com/read/29351497/screen-targeting-lung-and-prostate-cancer-oncogene-identifies-novel-inhibitors-of-rgs17-and-problematic-chemical-substructures
#1
Christopher R Bodle, Josephine H Schamp, Joseph B O'Brien, Michael P Hayes, Meng Wu, Jonathan A Doorn, David L Roman
Regulator of G protein signaling (RGS) proteins temporally regulate heterotrimeric G protein signaling cascades elicited by G protein-coupled receptor activation and thus are essential for cell homeostasis. The dysregulation of RGS protein expression has been linked to several pathologies, spurring discovery efforts to identify small-molecule inhibitors of these proteins. Presented here are the results of a high-throughput screening (HTS) campaign targeting RGS17, an RGS protein reported to be inappropriately upregulated in several cancers...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29351464/vitamin-d-and-regulation-of-vascular-cell-function
#2
Nasim Jamali, Christine M Sorenson, Nader Sheibani
Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for treatment of various types of cancer and chronic diseases. We previously showed that the active form of vitamin D (1, 25(OH)2D3) is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#3
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29350683/ccat1-stimulation-of-the-symmetric-division-of-nsclc-stem-cells-through-activation-of-the-wnt-signalling-cascade
#4
Chongwen Xu, Guodong Xiao, Boxiang Zhang, Meng Wang, Jichang Wang, Dapeng Liu, Jing Zhang, Hong Ren, Xin Sun
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortalities worldwide, yet this condition remains a poorly understood malignancy, and the subgroup of cancer stem cells (CSCs) leading to therapeutic resistance and adverse prognosis have not been well studied. CSCs frequently undergo symmetric division, which facilitates expansion of the stem cell pool, contributing to long-term relapse and therapy failure. CCAT1 could act as a miRNA sponge to influence downstream genes; however, its roles in NSCLC stem cell are unclear...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29350680/effects-of-microrna-135a-on-the-epithelial-mesenchymal-transition-migration-and-invasion-of-bladder-cancer-cells-by-targeting-gsk3%C3%AE-through-the-wnt-%C3%AE-catenin-signaling-pathway
#5
Xia-Wa Mao, Jia-Quan Xiao, Zhong-Yi Li, Yi-Chun Zheng, Nan Zhang
This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#6
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#7
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350049/targeted-and-off-target-bystander-and-abscopal-effects-of-radiation-therapy-redox-mechanisms-and-risk-benefit-analysis
#8
Jean-Pierre Pouget, Alexandros G Georgakilas, Jean-Luc Ravanat
Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29349903/gp73-promotes-invasion-and-metastasis-of-bladder-cancer-by-regulating-the-epithelial-mesenchymal-transition-through-the-tgf-%C3%AE-1-smad2-signalling-pathway
#9
Han-Jie Yang, Ge-Liang Liu, Bo Liu, Tian Liu
This study investigated the effects of Golgi membrane protein 73 (GP73) on the epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and metastasis through the TGF-β1/Smad2 signalling pathway. Paired bladder cancer and adjacent tissue samples (102) and normal bladder tissue samples (106) were obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected and assigned to blank, negative control (NC), TGF-β, thrombospondin-1 (TSP-1), TGF-β1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+ pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups...
January 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29349300/tensile-forces-drive-a-reversible-fibroblast-to-myofibroblast-transition-during-tissue-growth-in-engineered-clefts
#10
Philip Kollmannsberger, Cécile M Bidan, John W C Dunlop, Peter Fratzl, Viola Vogel
Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor-β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29348886/frk-inhibits-breast-cancer-cell-migration-and-invasion-by-suppressing-epithelial-mesenchymal-transition
#11
Yetunde Ogunbolude, Chenlu Dai, Edward T Bagu, Raghuveera Kumar Goel, Sayem Miah, Joshua MacAusland-Berg, Chi Ying Ng, Rajni Chibbar, Scott Napper, Leda Raptis, Frederick Vizeacoumar, Franco Vizeacoumar, Keith Bonham, Kiven Erique Lukong
The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348883/spatial-habitats-from-multiparametric-mr-imaging-are-associated-with-signaling-pathway-activities-and-survival-in-glioblastoma
#12
Katherine Dextraze, Abhijoy Saha, Donnie Kim, Shivali Narang, Michael Lehrer, Anita Rao, Saphal Narang, Dinesh Rao, Salmaan Ahmed, Venkatesh Madhugiri, Clifton David Fuller, Michelle M Kim, Sunil Krishnan, Ganesh Rao, Arvind Rao
Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity, impacting response to treatment and overall survival time of 12-15 months. To study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were analyzed to characterize tumor-derived spatial habitats for their relationship with outcome (overall survival) and to identify their molecular correlates (i.e., determine associated tumor signaling pathways correlated with imaging-derived habitat measurements)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348878/identification-of-cancer-prognosis-associated-functional-modules-using-differential-co-expression-networks
#13
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348860/silencing-ror1-and-ror2-inhibits-invasion-and-adhesion-in-an-organotypic-model-of-ovarian-cancer-metastasis
#14
Claire Henry, Neville Hacker, Caroline Ford
OBJECTIVE: Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted in both the tumour and stromal compartments of ovarian cancer patient tissue samples. In vitro studies have suggested these receptors play a role in ovarian cancer metastasis. However, these previous studies have utilised simple 2D in vitro models to investigate cancer cell growth and migration, which does not allow investigation of stromal involvement in Wnt driven metastasis. AIM: To investigate targeting ROR1 and ROR2 using a primary co-culture 3D model of epithelial ovarian cancer dissemination to the omentum...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348850/novel-indazole-based-small-compounds-enhance-trail-induced-apoptosis-by-inhibiting-the-mkk7-tiprl-interaction-in-hepatocellular-carcinoma
#15
Ji-Yong Yoon, Jeong-Ju Lee, Sujin Gu, Myoung Eun Jung, Hyun-Soo Cho, Jung Hwa Lim, Soo Young Jun, Jun-Ho Ahn, Ju-Sik Min, Min-Hyuk Choi, Su-Jin Jeon, Yong-Jae Lee, Areum Go, Yun-Jeong Heo, Cho-Rok Jung, Gildon Choi, Kwangho Lee, Moon-Kook Jeon, Nam-Soon Kim
Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Although various treatments, such as surgery and chemotherapy, have been developed, a novel alternative therapeutic approach for HCC therapy is urgently needed. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent, but many cancer cells are resistant to TRAIL-induced apoptosis. To help overcome TRAIL resistance in HCC cancer cells, we have identified novel chemical compounds that act as TRAIL sensitizers...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348847/distinct-roles-of-traf6-and-tak1-in-the-regulation-of-adipocyte-survival-thermogenesis-program-and-high-fat-diet-induced-obesity
#16
Yann S Gallot, Joseph D McMillan, Guangyan Xiong, Kyle R Bohnert, Alex R Straughn, Bradford G Hill, Ashok Kumar
Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348845/decreased-expression-of-the-long-non-coding-rna-slc7a11-as1-predicts-poor-prognosis-and-promotes-tumor-growth-in-gastric-cancer
#17
Yajun Luo, Cheng Wang, Peng Yong, Pengcheng Ye, Zilin Liu, Zhiming Fu, Fei Lu, Wanping Xiang, Wang Tan, Jiangwei Xiao
Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth in vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11 via the ASK1-p38MAPK/JNK signaling pathway...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348842/ddefl1-correlated-with-rho-gtpases-activity-in-breast-cancer
#18
Xiaoyun Mao, Chuifeng Fan, Xinmiao Yu, Bo Chen, Feng Jin
DDEFL1 is related to maintaining a limiting amount of ARF6 in GTP-loaded form by accelerating its GTP hydrolysis activity, which has been implicated in hepatocellular cancer pathogenesis and lung cancer development. We investigated DDEFL1 expression in breast cancer and paired normal breast tissues by immunohistochemistry and found that DDEFL1 expression was significantly associated with tumor size, lymph node metastasis, high content of elastosis and TNM stage but not with menopausal status or age. We detected the mRNA and protein expression of DDEFL1 in breast cancer cell lines by Western blotting and quantitative real-time PCR (qRT-PCR)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348829/roflumilast-restores-camp-pka-creb-signaling-axis-for-ftmt-mediated-tumor-inhibition-of-ovarian-cancer
#19
Shipeng Gong, Yongning Chen, Fanliang Meng, Yadi Zhang, Huan Wu, Fei Wu
The abrogation of cAMP generation by overexpression of PDE isoforms promotes the inflammatory pathology, and the PDE inhibitors have showed the potential anti-inflammation effects in clinical. However, the function of PDE inhibitors in cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest in two ovarian cancer cell lines OVCAR3 and SKOV3...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348827/molecular-genetic-profiling-and-high-throughput-in-vitro-drug-screening-in-nut-midline-carcinoma-an-aggressive-and-fatal-disease
#20
Anja Stirnweiss, Joyce Oommen, Rishi S Kotecha, Ursula R Kees, Alex H Beesley
NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival typically less than seven months, that can arise in people of any age. Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin-binding partner, typically the bromodomain-containing protein BRD4. However, little is known about other genetic aberrations in this disease. In this study, we used a unique panel of cell lines to describe the molecular-genetic features of NMC. Next-generation sequencing identified a recurring high-impact mutation in the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from mutation-signature and network analyses consistent with a general failure in DNA-repair...
December 22, 2017: Oncotarget
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