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https://www.readbyqxmd.com/read/28551845/sostdc1-inhibits-follicular-thyroid-cancer-cell-proliferation-migration-and-emt-via-suppressing-pi3k-akt-and-mapk-erk-signaling-pathways
#1
Qinyi Zhou, Jun Chen, Jialin Feng, Yanan Xu, Wenjie Zheng, Jiadong Wang
The sclerostin domain containing protein 1 (SOSTDC1) is a cell signaling regulator involved in cell physiology and pathology. SOSTDC1 is known to have a suppressive effect on certain kinds of cancer. However, the role of SOSTDC1 in follicular thyroid cancer (FTC) remains unknown. We aimed to investigate if the expression of SOSTDC1 plays any roles in carcinogenesis and metastasis of FTC. We found a significantly down-regulated SOSTDC1 expression in follicular thyroid cancer samples. In addition, our data showed that ectopic expression of SOSTDC1 dramatically inhibited thyroid cancer cell proliferation in vitro and in nude mice...
May 27, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28551702/alpha-7-nicotinic-receptor-signaling-pathway-participates-in-the-neurogenesis-induced-by-chat-positive-neurons-in-the-subventricular-zone
#2
Jianping Wang, Zhengfang Lu, Xiaojie Fu, Di Zhang, Lie Yu, Nan Li, Yufeng Gao, Xianliang Liu, Chunmao Yin, Junji Ke, Liyuan Li, Mengmeng Zhai, Shiwen Wu, Jiahong Fan, Liang Lv, Junchao Liu, Xuemei Chen, Qingwu Yang, Jian Wang
Choline acetyltransferase-positive (ChAT(+)) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine...
May 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28551559/crotonaldehyde-induces-autophagy-mediated-cytotoxicity-in-human-bronchial-epithelial-cells-via-pi3k-ampk-and-mapk-pathways
#3
Limeng Wang, Xiang Li, Zhihua Yang, Xiujie Pan, Xingyu Liu, Maoxiang Zhu, Jianping Xie
Crotonaldehyde is an ubiquitous hazardous pollutant in the environment which can be produced naturally, artificially and endogenously. Acute exposure of crotonaldehyde was reported to induce severe lung injury in humans and experimental animals. However, the exact toxicity mechanisms of crotonaldehyde in organisms have not been fully explored. In the present study, we explored the role autophagy played in the cytotoxicity induced by crotonaldehyde in human bronchial epithelial cells (BEAS-2B), and the pathways that mediated autophagy, including the phosphatidylinositol 3-kinase (PI3K) pathway, the AMP-activated protein kinase (AMPK) pathway and the mitogen-activated protein kinase (MAPK) pathways, were examined and validated...
May 25, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28551389/mutation-analysis-of-ctnnb1-gene-and-the-ras-pathway-genes-kras-nras-braf-and-pik3ca-in-eyelid-sebaceous-carcinomas
#4
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe
Sebaceous carcinoma (SC) represents a rare, aggressive eyelid malignancy with poor prognosis and is a possible component of Muir-Torre syndrome. However, genetic features as driver mutations or potential therapeutic targets are not fully elucidated. Recent a few studies have shown that SCs have concurrently multiple mutations including RAS/RAF/MAPK and PI3K/Akt pathways via next-generation sequencing in western population. Because we recently demonstrated absence of KRAS mutations in Korean eyelid SCs, we extended our previous study to the analysis of NRAS, BRAF, PIK3CA, and CTNNB1 mutations, and the examination of related protein expressions in 15 eyelid SCs...
March 1, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28551103/inhibition-of-phosphatidylinositol-3-kinase-by-the-furanosesquiterpenoid-hibiscone-c
#5
Caroline Besley, Dena P Rhinehart, Taylor Ammons, Brian C Goess, Jason S Rawlings
The phosphatidylinositol-3-kinase (PI3K) pathway regulates cellular metabolism and is upregulated in many cancers, making it an attractive chemotherapeutic target. Wortmannin is a potent inhibitor of PI3K; however, its potential as a chemotherapeutic is limited due to its instability, lack of selectivity, and lengthy chemical synthesis. In contrast, hibiscone C, a structurally simpler and less studied member of the furanosteroid family, has been expediently prepared by total synthesis. We demonstrate that hibiscone C competitively inhibits PI3K activity in intact cells, slows proliferation, and induces cell death...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28550907/analysis-of-pik3ca-mutations-and-pi3k-pathway-proteins-in-advanced-gastric-cancer
#6
Chie Ito, Satoshi S Nishizuka, Kazuyuki Ishida, Noriyuki Uesugi, Tamotsu Sugai, Gen Tamura, Keisuke Koeda, Akira Sasaki
BACKGROUND: Although surgery and chemotherapy have extended advanced gastric cancer patient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancer patients. METHODS: A retrospective cohort of 160 advanced gastric cancer patients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival...
May 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#7
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28550116/myeloid-derived-cells-in-prostate-cancer-progression-phenotype-and-prospective-therapies
#8
REVIEW
Zoila Lopez-Bujanda, Charles G Drake
Prostate cancer is the second most common cause of cancer mortality in men in the United States. As is the case for other tumor types, accumulating evidence suggests an important role for myeloid-derived cells in the promotion and progression of prostate cancer. Here, we briefly describe myeloid-derived cells that interact with tumor cells and what is known about their immune suppressive function. We next discuss new evidence for tumor cell-mediated myeloid infiltration via the PI3K/PTEN/AKT signaling pathway and an alternative mechanism for immune evasion that may be regulated by an endoplasmic reticulum stress response...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550065/exceptional-durable-response-to-everolimus-in-a-patient-with-biphenotypic-breast-cancer-harboring-an-stk11-variant
#9
Christine A Parachoniak, Andrew Rankin, Bernadette Gaffney, Ryan Hartmaier, Dan Spritz, Rachel L Erlich, Vincent A Miller, Deborah Morosini, Phil Stephens, Jeffrey S Ross, John Keech, Juliann Chmielecki
Metastatic triple negative breast cancer comprises 12-17% of breast cancers and carries a poor prognosis relative to other breast cancer subtypes. Treatment options in this disease are largely limited to systemic chemotherapy. A majority of clinical studies assessing efficacy of targeted therapeutics (e.g. the mTOR inhibitor everolimus) in advanced breast cancer patients have not utilized predictive genomic biomarker-based selection and have reported only modest improvement in clinical outcome relative to standard of care...
May 26, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28549860/crude-terpene-glycoside-component-from-radix-paeoniae-rubra-protects-against-isoproterenol-induced-myocardial-ischemic-injury-via-activation-of-the-pi3k-akt-mtor-signaling-pathway
#10
Zhongcheng Ke, Gang Wang, Lei Yang, Huihui Qiu, Hao Wu, Mei Du, Juan Chen, Jie Song, Xiaobin Jia, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Radix paeoniae rubra, also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis. It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown...
May 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28549597/prolactin-receptor-targeting-in-breast-and-prostate-cancers-new-insights-into-an-old-challenge
#11
REVIEW
Vincent Goffin
In the era of precision medicine, the identification of new targets is a constant challenge to improve cancer therapy. Preclinical investigations, epidemiological studies and analyses of tissue specimens from patients strongly support the contribution of prolactin receptor (PRLR) signaling to breast and prostate tumorigenesis and cancer progression. Although a clear causative link with mutations of the genes encoding prolactin or its receptor is lacking, increased PRLR signaling in these cancers can be assessed by the overexpression of cognate proteins and is often confirmed by over-activation of downstream signaling effectors...
May 23, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28549531/targeting-the-akt-gsk-3-bcl-2-axis-in-acute-myeloid-leukemia
#12
REVIEW
Maria Rosaria Ricciardi, Simone Mirabilii, Roberto Licchetta, Monica Piedimonte, Agostino Tafuri
Over the last few decades, there has been significant progress in the understanding of the pathogenetic mechanisms of the Acute Myeloid Leukemia (AML). However, despite important advances in elucidating molecular mechanisms, the treatment of AML has not improved significantly, remaining anchored at the standard chemotherapy regimen "3 + 7", with the prognosis of patients remaining severe, especially for the elderly and for those not eligible for transplant procedures. The biological and clinical heterogeneity of AML represents the major obstacle that hinders the improvement of prognosis and the identification of new effective therapeutic approaches...
May 19, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28549347/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#13
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549342/mgr1-antigen-37-kda-laminin-receptor-precursor-promotes-cellular-prion-protein-induced-multi-drug-resistance-of-gastric-cancer
#14
Guanhong Luo, Weijie Wang, Qiong Wu, Yuanyuan Lu, Tao Su, Nan Gu, Kai Li, Jingbo Wang, Rui Du, Xiaodi Zhao, Xiaohua Li, Rui Fan, Hongbo Zhang, Yongzhan Nie, Xinmin Zhou, Yongquan Shi, Jie Liang, Xin Wang, Daiming Fan
Cellular prion protein (PrPC), the infective agent of transmissible spongiform encephalopathies, is thought to be related to several cellular physiological and physiopathological processes. We have previously reported that PrPC participates in multi-drug-resistance of gastric cancer. As the salient ligand molecule of PrP for participating in internalization and propagation of the scrapie form of prion protein (PrPSc), 37 kDa laminin receptor precursor protein (37LRP) shared the same gene coding sequence of MGr1-Ag, another protein previously found to be involved in multi-drug-resistance of gastric cancer in our lab...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549244/ll-37-induced-human-mast-cell-activation-through-g-protein-coupled-receptor-mrgx2
#15
Yangyang Yu, Yuanyuan Zhang, Yarui Zhang, Yihong Lai, Wenwen Chen, Zhangang Xiao, Wei Zhang, Meiling Jin, Bo Yu
Human LL-37 is an important class of cationic antimicrobial peptide (CAP) that is known to stimulate mast cell activation. While many studies have been conducted on LL-37, to date little is known about the functional receptors for LL-37-induced human mast cell activation, in particular in terms of the release of de novo synthesized mediators. Thus, the aim of the present study is to identify the functional receptors for LL-37-induced human mast cell activation in terms of the degranulation and release of de novo synthesized mediators and investigate the downstream signalling pathways involved in mast cell activation...
May 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28549032/expression-of-phosphoinositide-3-kinase-p110%C3%AE-and-p110%C3%AE-subunits-and-pik3ca-mutation-in-patients-with-advanced-gastric-carcinoma
#16
Kyungeun Kim, Hyoun Wook Lee
Activation of phosphoinositide 3-kinase (PI3K) is pivotal for the activity of the oncogenic PI3K/AKT signaling pathway. This study assessed the expression of 2 PI3K isoform proteins, p110α and p110β, and PIK3CA mutational status in advanced gastric carcinoma (AGC) and their correlation with clinicopathologic factors. Tissue microarray blocks were generated from 99 AGCs and immunohistochemically stained for p110α and p110β. Analysis of mutations in the PIK3CA gene, which encodes p110α, was performed using the PNAClamp PIK3CA Mutation Detection kit...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28548952/bisphenol-a-exposure-promotes-htr-8-svneo-cell-migration-and-impairs-mouse-placentation-involving-upregulation-of-integrin-%C3%AE-1-and-mmp-9-and-stimulation-of-mapk-and-pi3k-signaling-pathways
#17
Xi Lan, Li-Juan Fu, Jun Zhang, Xue-Qing Liu, Hui-Jie Zhang, Xue Zhang, Ming-Fu Ma, Xue-Mei Chen, Jun-Lin He, Lian-Bing Li, Ying-Xiong Wang, Yu-Bin Ding
In this study, we investigated the effect of Bisphenol A (BPA), an endocrine-disrupting chemical, on the migration of human trophoblasts and mouse placentation by using the primary extravillous trophoblast (EVT) and its cell line HTR-8/SVneo, villous explant cultures, and pregnant mice. BPA increased EVT motility and the outgrowth of villous explants in a dose-dependent manner. BPA also increased the protein levels of integrin-β1 and matrix metalloproteinase (MMP)-9 in human EVTs. Low-dose BPA (≤50 mg) increased the protein levels of MMP-9 and MMP-2 as well as integrin-β1 and integrin-α5 in mouse placenta and decreased the proportion of the labyrinth and spongiotrophoblast layers...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548939/netrin-1-promotes-gastric-cancer-cell-proliferation-and-invasion-via-the-receptor-neogenin-through-pi3k-akt-signaling-pathway
#18
Kai Yin, Linjun Wang, Xuan Zhang, Zhongyuan He, Yiwen Xia, Jianghao Xu, Song Wei, Bowen Li, Zheng Li, Guangli Sun, Qing Li, Hao Xu, Zekuan Xu
Netrin-1 is a laminin-related protein found to promote proliferation and invasion in multiple types of cancers. Recent studies have identified the function role of netrin-1 in several cancers; however, the influence of netrin-1 in human gastric cancer(GC) remains largely unknown. In this study, we found netrin-1 was upregulated in human GC tissues, where its expression correlated inversely with cancer stage and lymph node metastasis. We detected netrin-1 and its receptor knockdown significantly suppressed GC cells proliferation and invasion, while overexpression netrin-1 reversed these effects...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#19
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28548125/next-generation-sequencing-based-molecular-characterization-of-primary-urinary-bladder-adenocarcinoma
#20
Somak Roy, Dinesh Pradhan, Wayne L Ernst, Stephanie Mercurio, Yana Najjar, Rahul Parikh, Anil V Parwani, Reetesh K Pai, Rajiv Dhir, Marina N Nikiforova
Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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