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https://www.readbyqxmd.com/read/28329645/frequent-somatic-mutations-of-chromatin-remodeling-genes-in-metastatic-cutaneous-squamous-cell-carcinoma
#1
Amanda Ewart Toland
Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but is typically correlated with high survival rates and low rates of metastasis. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals are estimated to die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations with potential therapeutic benefit...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28328116/brain-morphology-in-children-with-nevoid-basal-cell-carcinoma-syndrome
#2
Tadashi Shiohama, Katsunori Fujii, Toshiyuki Miyashita, Hiromi Mizuochi, Hideki Uchikawa, Naoki Shimojo
Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28327554/ppar%C3%AE-%C3%AE-a-novel-regulator-for-vascular-smooth-muscle-cells-phenotypic-modulation-and-vascular-remodeling-after-subarachnoid-hemorrhage-in-rats
#3
Hongrong Zhang, Li Jiang, Zongduo Guo, Jianjun Zhong, Jingchuan Wu, Junchi He, Han Liu, Zhaohui He, Haitao Wu, Chongjie Cheng, Xiaochuan Sun
Cerebral vascular smooth muscle cell (VSMC) phenotypic switch is involved in the pathophysiology of vascular injury after aneurysmal subarachnoid hemorrhage (aSAH), whereas the molecular mechanism underlying it remains largely speculative. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has been implicated to modulate the vascular cells proliferation and vascular homeostasis. In the present study, we investigated the potential role of PPARβ/δ in VSMC phenotypic switch following SAH. Activation of PPARβ/δ by GW0742 and adenoviruses PPARβ/δ (Ad-PPARβ/δ) significantly inhibited hemoglobin-induced VSMC phenotypic switch...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327179/pterostilbene-prevents-akt-erk-axis-mediated-polymerization-of-surface-fibronectin-on-suspended-lung-cancer-cells-independently-of-apoptosis-and-suppresses-metastasis
#4
Ying-Jan Wang, Jing-Fang Lin, Li-Hsin Cheng, Wen-Tsan Chang, Ying-Hsien Kao, Ming-Min Chang, Bour-Jr Wang, Hung-Chi Cheng
BACKGROUND: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger pro-apoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored. METHODS: We depleted suspended Lewis lung carcinoma (LLC) cells of polyFN by silencing the endogenous FN expression or pterostilbene (PS) to examine whether metastasis of lung cancer cells could thus be suppressed...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28324760/trpv1-agonism-inhibits-endothelial-cell-inflammation-via-activation-of-enos-no-pathway
#5
Youping Wang, Lin Cui, Hui Xu, Suxiao Liu, Feiyun Zhu, Fengna Yan, Si Shen, Mingjun Zhu
BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca(2+)-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#6
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324019/no-mediated-regulation-of-glut-by-t3-and-fsh-in-rat-granulosa-cells
#7
Ye Tian, Yu Ding, Juan Liu, Dai Heng, Kaili Xu, Wenbo Liu, Cheng Zhang
Thyroid hormones (THs) are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. Here, we present evidence that T3 and FSH co-treatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake...
March 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#8
ZhengRu Huang, ZiZhong Hu, Ping Xie, QingHuai Liu
Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm...
2017: PloS One
https://www.readbyqxmd.com/read/28323103/cr-vi-induces-cytotoxicity-in-vitro-through-activation-of-ros-mediated-endoplasmic-reticulum-stress-and-mitochondrial-dysfunction-via-the-pi3k-akt-signaling-pathway
#9
Yujing Zhang, Fang Xiao, Xinmin Liu, Kaihua Liu, Xiaoxin Zhou, Caigao Zhong
The occupational and environmental toxicant hexavalent chromium [Cr(VI)] can cause severe damage to the liver; however, the exact mechanisms associated with its toxicity have not been thoroughly demonstrated. In the present study, the underlying mechanisms of Cr(VI)-induced hepatotoxicity were investigated. Our results showed that Cr(VI) inhibited the growth and proliferation of L-02 hepatocytes. Further study revealed that Cr(VI) significantly induced S-phase cell cycle arrest and apoptosis accompanying with the overproduction of reactive oxygen species (ROS)...
March 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#10
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic Colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR moAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322991/thyroid-hormone-induce-a-p53-dependent-dna-damage-through-pi3k-akt-activation-in-sperm
#11
Hong Xian, Fang Wang, Wending Teng, Dong Yang, Ming Zhang
Accumulating evidences showed that thyroid hormone was participated in the functioning of the reproductive system, and an elevated level of thyroid hormones had a negative impact on reproductive system. However, the molecular basis for this observation still remains to be fully understood. Here, we show that l-Thyroxine significantly impaired human sperm motility. The molecular basis showed that thyroxine receptor stimulation triggers Phosphatidyl Inositol 3-kinase (PI3K)/Akt signaling activation leading to the E3 ligase MDM2 phosphorylation at serine 166, which directly interacted with p53 for degradation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28322787/aurka-promotes-cancer-metastasis-by-regulating-epithelial-mesenchymal-transition-and-cancer-stem-cell-properties-in-hepatocellular-carcinoma
#12
Chenlin Chen, Guangyuan Song, Jue Xiang, Hongcheng Zhang, Shaoyun Zhao, Yinchu Zhan
AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development; however, its role and underlying mechanisms in the metastasis of hepatocellular carcinoma (HCC) remain unknown. In this study, We found that AURKA was up-regulated in HCC tissues and correlated with pathological stage and distant metastasis. Further found that AURKA was involved in the cancer metastases after radiation in HCC. While overexpression of AURKA induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) behaviors though PI3K/AKT pathway, silencing AURKA suppressed radiation-enhanced cell invasiveness of HCC...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322778/down-regulation-of-cyclin-dependent-kinase-4-and-mapk-through-estrogen-receptor-mediated-cell-cycle-arrest-in-human-breast-cancer-induced-by-gold-nanoparticle-tagged-toxin-protein-nkct1
#13
Tanmoy Bhowmik, Antony Gomes
AIM: The aim of this study was to determine whether gold nanoparticles conjugated cytotoxic protein NKCT1 (GNP-NKCT1) acted through the estrogen receptor mediated pathway in MCF-7 cells and to establish the MAPK and PI3k/Akt signal transduction pathway. METHODS: Apoptosis was done by flow cytometry. BrdU incorporation and nuclear proliferating antigen was measured by flow cytometry. Wound healing assay along with matrigel chamber invasion and migration was done...
March 17, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28322459/effects-of-microrna-19b-on-the-proliferation-apoptosis-and-migration-of-wilms-tumor-cells-via-the-pten-pi3k-akt-signaling-pathway
#14
Ge-Liang Liu, Han-Jie Yang, Bo Liu, Tian Liu
Wilms' tumor (WT) is a most common renal cancer that occurs among children, and microRNA-19b (miR-19b) usually participates in various human cancers. Importantly, the PTEN/PI3K/Akt signaling pathway plays a key role in cell apoptosis, growth and proliferation. Thus, our present study aims to investigate the effect of miR-19b on the PTEN/PI3K/Akt signaling pathway during WT cell proliferation, migration and apoptosis. WT tissues and adjacent normal tissues from WT patients were collected. qRT-PCR was applied to detect miR-19b expression in both the WT tissues and the adjacent normal tissues, immunohistochemistry was applied to detect the protein expressions of PTEN, P13K and p-Akt, SK-NEP-1 cells were divided into the blank, negative control (NC), miR-19b mimics and miR-19b inhibitors groups...
March 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28322249/the-protective-effects-of-shikonin-on-hepatic-ischemia-reperfusion-injury-are-mediated-by-the-activation-of-the-pi3k-akt-pathway
#15
Tong Liu, QingHui Zhang, Wenhui Mo, Qiang Yu, Shizan Xu, Jingjing Li, Sainan Li, Jiao Feng, Liwei Wu, Xiya Lu, Rong Zhang, Linqiang Li, Keran Cheng, Yuqing Zhou, Shunfeng Zhou, Rui Kong, Fan Wang, Weiqi Dai, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Yan Zhao, Chuanyong Guo
Hepatic ischemia/reperfusion (I/R) injury, which can result in severe liver injury and dysfunction, occurs in a variety of conditions such as liver transplantation, shock, and trauma. Cell death in hepatic I/R injury has been linked to apoptosis and autophagy. Shikonin plays a significant protective role in ischemia/reperfusion injury. The purpose of the present study was to investigate the protective effect of shikonin on hepatic I/R injury and explore the underlying mechanism. Mice were subjected to segmental (70%) hepatic warm ischemia to induce hepatic I/R injury...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321769/n-propargyl-caffeamide-paca-ameliorates-dopaminergic-neuronal-loss-and-motor-dysfunctions-in-mptp-mouse-model-of-parkinson-s-disease-and-in-mpp-induced-neurons-via-promoting-the-conversion-of-prongf-to-ngf
#16
Dan Luo, Jia Zhao, Yuanyuan Cheng, Simon Ming-Yuen Lee, Jianhui Rong
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days...
March 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28321180/multiple-kinases-involved-in-the-nicotinic-modulation-of-gamma-oscillations-in-the-rat-hippocampal-ca3-area
#17
JianGang Wang, XiaoLong He, Fangli Guo, XiangLin Cheng, Yali Wang, XiaoFang Wang, ZhiWei Feng, Martin Vreugdenhil, ChengBiao Lu
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28320862/differential-involvement-of-the-microtubule-cytoskeleton-in-insulin-receptor-substrate-1-irs-1-and-irs-2-signaling-to-akt-determines-response-to-microtubule-disruption-in-breast-carcinoma-cells
#18
Jose Mercado-Matos, Jennifer L Clark, Andrew J Piper, Jenny Janusis, Leslie M Shaw
The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor-1 receptor (IGF-1R) and its close family member the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28320338/the-allosteric-akt-inhibitor-mk2206-shows-a-synergistic-interaction-with-chemotherapy-and-radiotherapy-in-glioblastoma-spheroid-cultures
#19
Ravi S Narayan, Carlos A Fedrigo, Eelke Brands, Rogier Dik, Lukas J A Stalpers, Brigitta G Baumert, Ben J Slotman, Bart A Westerman, Godefridus J Peters, Peter Sminia
BACKGROUND: Glioblastoma multiforme (GBM) is the most common, invasive and deadly primary type of malignant brain tumor. The Phosphatidylinositol-3-Kinase/AKT (PI3K/AKT) pathway is highly active in GBM and has been associated with increased survival and resistance to therapy. The aim of this study is to investigate the effects of AKT inhibition in combination with the current standard of care which consists of irradiation and temozolomide (TMZ) on human malignant glioma cells growing adherent and as multicellular spheroids in vitro...
March 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28320107/pre-conditioning-with-tanshinone-iia-attenuates-the-ischemia-reperfusion-injury-caused-by-liver-grafts-via-regulation-of-hmgb1-in-rat-kupffer-cells
#20
Xuanfei Li, Yakun Wu, Wenfeng Zhang, Jianping Gong, Yao Cheng
OBJECTIVE: We have evaluated the protective mechanism of tanshinone IIA in ischemia/reperfusion injury (IRI) induced by liver grafts, revealing novel supplementary immunotherapy for liver transplantation. METHODS: The tanshinone IIA preconditioning group (TP group) was pretreated with tanshinone IIA via intraperitoneal injection for 1 week before receiving orthotopic liver transplantation with hepatic arterial ischemia for 30min. The sham-operation group (SO group), control graft group (CG group) and IRI group were pretreated with an equivalent volume of normal saline...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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