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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
#1
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/29778422/sp1-induced-upregulation-of-lncrna-pandar-predicts-adverse-phenotypes-in-retinoblastoma-and-regulates-cell-growth-and-apoptosis-in-vitro-and-in-vivo
#2
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/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#3
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/29777795/sirna-in-ovarian-cancer-delivery-strategies-and-targets-for-therapy
#4
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
#5
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
#6
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/29777710/mir-616-3p-promotes-angiogenesis-and-emt-in-gastric-cancer-via-the-pten-akt-mtor-pathway
#7
Zhen-Hua Wu, Chen Lin, Chen-Chen Liu, Wei-Wei Jiang, Ming-Zhu Huang, Xin Liu, Wei-Jian Guo
Dysregulation of microRNAs has been demonstrated to be involved in a variety of biological events related to cancer, including proliferation, metastasis, angiogenesis and immune escape. miR-616-3p is located on the chromosome region 12q13.3, however, its potential role and clinical implications in gastric cancer remain poorly understood. The current study aimed to investigate the potential role of miR-616-3p in gastric cancer. The results showed that miR-616-3p was up-regulated in cancer tissues. Higher expression of miR-616-3p in tumor tissues also predicted poor prognosis...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#8
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777575/lgr5-promotes-epithelial-ovarian-cancer-proliferation-metastasis-and-epithelial-mesenchymal-transition-through-the-notch1-signaling-pathway
#9
Wenxue Liu, Jing Zhang, Xupei Gan, Fangqian Shen, Xiaoming Yang, Na Du, Dandan Xia, Lei Liu, Lianqiao Qiao, Jufang Pan, Yunyan Sun, Xiaowei Xi
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR5 in human EOC. We evaluated LGR5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR, Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch-wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells...
May 18, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#10
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29775310/fragment-based-discovery-of-a-potent-orally-bioavailable-inhibitor-which-modulates-the-phosphorylation-and-catalytic-activity-of-erk1-2
#11
Tom D Heightman, Valerio Berdini, Hannah Braithwaite, Ildiko Maria Buck, Megan Cassidy, Juan Castro, Aurelie Courtin, James E H Day, Charlotte East, Lynsey Fazal, Brent Graham, Charlotte M Griffiths-Jones, John F Lyons, Vanessa Martins, Sandra Muench, Joanne M Munck, David Norton, Marc O'Reilly, Nick Palmer, Puja Pathuri, Michael Reader, David C Rees, Sharna J Rich, Caroline Richardson, Harpreet Saini, Neil T Thompson, Nicola G Wallis, Hugh Walton, Nicola E Wilsher, Alison J-A Woolford, Michael Cooke, David Cousin, Stuart Onions, Jonathan Shannon, John Watts, Christopher W Murray
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signalling through ERK1/2. Here we describe the fragment based generation of ERK1/2 inhibitors which block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774792/hypofractionated-radiotherapy-is-superior-to-conventional-fractionation-in-an-orthotopic-model-of-anaplastic-thyroid-cancer
#12
Ayman J Oweida, Andy Phan, Benjamin Vancourt, Tyler Robin, Mohammad K Hararah, Shilpa Bhatia, Dallin Milner, Shelby Lennon, Laura Pike, David Raben, Bryan R Haugen, Nikita Pozdeyev, Rebecca E Schweppe, Sana D Karam
Anaplastic thyroid cancer is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment including radiation therapy and chemotherapy, response rates remain below 15% with a median time to progression of less than 3 months. Recent advances in radiotherapy delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative radiotherapy fractionation schedules for overcoming radioresistance...
May 18, 2018: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#13
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774079/long-non-coding-rnas-ac026904-1-and-uca1-a-one-two-punch-for-tgf-%C3%AE-induced-snai2-activation-and-epithelial-mesenchymal-transition-in-breast-cancer
#14
Guo-Yin Li, Wei Wang, Jian-Yong Sun, Bo Xin, Xiang Zhang, Ting Wang, Qian-Feng Zhang, Li-Bo Yao, Hua Han, Dai-Ming Fan, An-Gang Yang, Lin-Tao Jia, Lei Wang
Transforming growth factor-β (TGF-β) has received much attention as a major inducer of epithelial-mesenchymal transition (EMT) during cancer progression, mainly by activating a set of pleiotropic transcription factors including SNAI2/Slug. However, the involvement of long non-coding RNAs (lncRNAs) in TGF-β-induced Slug activation and EMT remains largely unknown. Methods: In this study, we used microarray analysis to compare lncRNA expression profiles between TGF-β treated and untreated breast cancer cells...
2018: Theranostics
https://www.readbyqxmd.com/read/29774072/twist-promotes-tumor-metastasis-in-basal-like-breast-cancer-by-transcriptionally-upregulating-ror1
#15
Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P Zhou, Jian Shi, Tiebang Kang
Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins...
2018: Theranostics
https://www.readbyqxmd.com/read/29773584/mechanisms-in-endocrinology-cell-cycle-regulation-in-adrenocortical-carcinoma
#16
Sofia Pereira, Mariana P Monteiro, Isabelle Bourdeau, Andre Lacroix, Duarte Pignatelli
Adrenocortical carcinomas are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers...
May 17, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29773367/reduction-active-polymeric-prodrug-micelles-based-on-%C3%AE-cyclodextrin-polyrotaxanes-for-triggered-drug-release-and-enhanced-cancer-therapy
#17
Shuang Bai, Meili Hou, Xiaoxiao Shi, Jiucun Chen, Xiaoqian Ma, Yong-E Gao, Yajun Wang, Peng Xue, Yuejun Kang, Zhigang Xu
As one of the medical polymers approved by US Food and Drug Administration (FDA), poly(ethylene glycol) has low toxicity, high stability, good biocompatibility, unique physical and chemical properties. Cyclodextrin is an ideal candidate as a drug carrier due to its special structures and characteristics. These two materials were successfully assembled through chemosynthesis in combination with the hydrophilic poly(ethylene glycol) methyl ether methacrylate (OEGMA) chain and hydrophobic polymeric camptothecin (CPT) chain by atom transfer radical polymerization (ATRP)...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29772554/antibodies-against-gpcr
#18
Carlotto Meyer, Harald Heidecke
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772527/a-novel-role-for-cd26-dipeptidyl-peptidase-iv-as-a-therapeutic-target
#19
Kei Ohnuma, Ryo Hatano, Eriko Komiya, Haruna Otsuka, Takumi Itoh, Noriaki Iwao, Yutaro Kaneko, Taketo Yamada, Nam H Dang, Chikao Morimoto
CD26 is a 110 kDa surface glycoprotein with intrinsic dipeptidyl peptidase IV activity that is expressed on numerous cell types and has a multitude of biological functions. The role of CD26 in immune regulation has been extensively characterized, with recent findings elucidating its linkage with signaling pathways and structures involved in T-lymphocyte activation as well as antigen presenting cell-T-cell interaction. In this paper, we will review emerging data on CD26-mediated immune regulation suggesting that CD26 may be an appropriate therapeutic target for the treatment of selected immune disorders as well as Middle East respiratory syndrome coronavirus...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772460/estrogen-receptor-negative-progesterone-receptor-positive-breast-cancer-nobody-s-land-or-just-an-artifact
#20
REVIEW
Michał Kunc, Wojciech Biernat, Elżbieta Senkus-Konefka
The estrogen receptor α (ER) and the progesterone receptor (PgR) are one of the most important prognostic and predictive immunohistochemical markers in breast cancer. Breast cancers may express various profiles of hormone receptors: ER(+)/PgR(+), ER(-)/PgR(-), ER(+)/PgR(-) and ER(-)/PgR(+). The existence of the latter profile is a matter of controversy since PgR expressions is induced by ER-dependent pathways in breast cancer cells. One of the most extensively propagated hypotheses trying to explain the origin of ER(-)/PgR(+) breast cancers claims that they are technical artifacts dependent on the immunohistochemical procedure...
May 14, 2018: Cancer Treatment Reviews
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