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https://www.readbyqxmd.com/read/28926938/integrin-activation-contributes-to-lower-cisplatin-sensitivity-in-mv3-melanoma-cells-by-inducing-the-wnt-signalling-pathway
#1
Maria B R Piva, Bastian Jakubzig, Gerd Bendas
BACKGROUND: integrins have been associated with the development of chemotherapy resistant tumour cells, mostly those of hematopoietic origin, by mediating the binding to the extracellular matrix. The relevance for solid tumour cells and the underlying mechanisms remain elusive. METHODS: using MTT assays, we detected the loss in cisplatin sensitivity of human MV3 melanoma cells upon integrin activation. Underlying cellular pathways were evaluated by flow cytometry...
September 16, 2017: Cancers
https://www.readbyqxmd.com/read/28919123/liraglutide-a-glucagon-like-peptide-1-receptor-agonist-facilitates-osteogenic-proliferation-and-differentiation-in-mc3t3-e1-cells-through-phosphoinositide-3-kinase-pi3k-protein-kinase-b-akt-extracellular-signal-related-kinase-erk-1-2-and-camp-protein-kinase
#2
Xuelun Wu, Shilun Li, Peng Xue, Yukun Li
Previous studies have proven that Glucagon-like peptide-1 (GLP-1) and its receptor agonist exert favorable anabolic effects on skeletal metabolism. However, whether GLP-1could directly impact osteoblast-mediated bone forming is still controversial, and the underlying molecular mechanism remains to be elucidated. Thus in this paper, we investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on murine MC3T3-E1 preosteoblasts proliferation and differentiation and explored the potential cellular basis...
September 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28911173/lithium-chloride-increases-cox-2-expression-and-pge2-production-in-a-human-granulosa-lutein-svog-cell-line-via-a-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#3
Long Bai, Hsun-Ming Chang, Jung-Chien Cheng, Guiyan Chu, Peter C K Leung, Gongshe Yang
Lithium chloride (LiCl) is widely prescribed for the treatment of bipolar disorders and is associated with a higher incidence of reproductive adverse effects. Cyclooxygenase (COX)-2 and its derivative, prostaglandin E2 (PGE2), play regulatory roles in the human ovulatory process. Whether LiCl affects ovulation by regulating COX2 expression and PGE2 production in the human ovary is still largely unknown. The aim of this study was to investigate the effect of LiCl on the expression of COX-2 and production of PGE2 in human granulosa-lutein (hGL) cells, as well as the mechanisms underlying this effect...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28905209/expression-differences-of-genes-in-the-pi3k-akt-wnt-b-catenin-shh-notch-and-mapk-signaling-pathways-in-cd34-hematopoietic-cells-obtained-from-chronic-phase-patients-with-chronic-myeloid-leukemia-and-from-healthy-controls
#4
R de Cássia Viu Carrara, A M Fontes, K J Abraham, M D Orellana, S K Haddad, P V B Palma, R A Panepucci, M A Zago, D T Covas
PURPOSE: The fusion gene BRC-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BRC-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls...
September 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28901482/detection-of-rack1-and-ctnnbl1%C3%A2-induced-activation-of-mouse-splenocytes-using-an-immunoprecipitation%C3%A2-based-technique
#5
Bohan Dong, Guangli Dai, Lei Xu, Damin Shi
Tumor cell lysates (TCLs) have been reported to induce antitumor immunity; however, it remains unclear which elements serve a role in this process. The present study identified 768 proteins that were upregulated in TCL prepared from Lewis lung cancer cells compared with the lysate from type II alveolar epithelial cells. Among the proteins that were upregulated in TCL, receptor for activated C kinase 1 (RACK1) and catenin β‑like 1 (CTNNBL1) are closely associated with cell proliferation and the inhibition of apoptosis...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900173/fgfr-inhibitor-azd4547-impedes-the-stemness-of-mammary-epithelial-cells-in-the-premalignant-tissues-of-mmtv-erbb2-transgenic-mice
#6
Qingxia Zhao, Amanda B Parris, Erin W Howard, Ming Zhao, Zhikun Ma, Zhiying Guo, Ying Xing, Xiaohe Yang
The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases (RTKs) regulates signaling pathways involved in cell proliferation and differentiation. Currently, the anti-tumor properties of FGFR inhibitors are being tested in preclinical and clinical studies. Nevertheless, reports on FGFR inhibitor-mediated breast cancer prevention are sparse. In this study, we investigated the anti-cancer benefits of AZD4547, an FGFR1-3 inhibitor, in ErbB2-overexpressing breast cancer models. AZD4547 (1-5 µM) demonstrated potent anti-proliferative effects, inhibition of stemness, and suppression of FGFR/RTK signaling in ErbB2-overexpressing human breast cancer cells...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900081/-mir-218-promoted-the-apoptosis-of-human-ovarian-carcinoma-cells-via-suppression-of-the-wnt-%C3%AE-catenin-signaling-pathway
#7
Y Huang, S-H Liang, L-B Xiang, X-T Han, W Zhang, J Tang, X-H Wu, M-Q Zhang
MicroRNA-218 (miR-218) is a short, noncoding RNA, with multiple biological functions. In this study, we aimed to investigate the potential effects of miR-218 on the apoptosis of human ovarian carcinoma cells and the underlying mechanisms by which miR-218 exerted its actions. After over-expressing miR-218 in human ovarian carcinoma (OVCAR3) cells, cell viability was determined by MTT method, cell apoptosis was observed by flow cytometry (FCM), mRNA expression of miR-218, Bcl2, Bax was measured by RT-PCR and protein expression levels of Wnt, tankyrase and β-catenin were quantified by Western blots...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28899495/cytotoxic-activities-of-telectadium-dongnaiense-and-its-constituents-by-inhibition-of-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Won Kyung Kim, Duc-Hiep Bach, Hyung Won Ryu, Jedo Oh, Hyen Joo Park, Ji-Young Hong, Hyuk-Hwan Song, Sangmi Eum, Tran The Bach, Sang Kook Lee
BACKGROUND: Wnt/β-catenin signaling pathway is a potential target for the treatment of human colon cancer. Thus, the inhibitory effects of various plant extracts on cell proliferation and Wnt signal transduction were evaluated to discover a Wnt signaling inhibitor. PURPOSE: The present study aimed to investigate the cytotoxicity involved in Wnt pathway of the MeOH extract from Telectadium dongnaiense bark (TDB) and to identify its bioactive constituents by bioassay-guided fractionation...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28895414/knockdown-of-tripartite-motif-containing-28-suppresses-the-migration-invasion-and-epithelial-mesenchymal-transition-in-ovarian-carcinoma-cells-through-down-regulation-of-wnt-%C3%AE-catenin-signaling-pathway
#9
B Deng, S Zhang, Y Zhang, Y Miao, X Meng, K Guo
Tripartite motif containing 28 (TRIM28) is a transcriptional corepressor of Kruppel-associated box zinc finger protein, which has been reported to participate in carcinogenesis. Nonetheless, whether TRIM28 plays a role in the metastasis of ovarian carcinoma (OC) is unclear and requires further investigation. In this study, two OC cell lines (A2780 and OVCAR-3) with stable low expression of TRIM28 were established via RNA interference. We found that the migratory and invasive ability of TRIM28-silenced OC cells significantly decreased...
September 12, 2017: Neoplasma
https://www.readbyqxmd.com/read/28894169/an-embryonic-system-to-assess-direct-and-indirect-wnt-transcriptional-targets
#10
Jahnavi Suresh, Nathan Harmston, Ka Keat Lim, Prameet Kaur, Helen Jingshu Jin, Jay B Lusk, Enrico Petretto, Nicholas S Tolwinski
During animal development, complex signals determine and organize a vast number of tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a β-catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that can be used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887323/atg5-mediates-a-positive-feedback-loop-between-wnt-signaling-and-autophagy-in-melanoma
#11
Abibatou Ndoye, Anna Budina-Kolomets, Curtis H Kugel, Marie R Webster, Amanpreet Kaur, Reeti Behera, Vito W Rebecca, Ling Li, Patricia A Brafford, Qin Liu, Y N Vashisht Gopal, Michael A Davies, Gordon B Mills, Xiaowei Xu, Hong Wu, Meenhard Herlyn, Michael C Nicastri, Jeffrey D Winkler, Maria S Soengas, Ravi K Amaravadi, Maureen E Murphy, Ashani T Weeraratna
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin...
September 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28884281/angiotensin-receptor-blockade-by-inhibiting-glial-activation-promotes-hippocampal-neurogenesis-via-activation-of-wnt-%C3%AE-catenin-signaling-in-hypertension
#12
Shahnawaz Ali Bhat, Ruby Goel, Shubha Shukla, Rakesh Shukla, Kashif Hanif
Hypertension is one of the major risk factors for central nervous system (CNS) disorders like stroke and Alzheimer's disease (AD). On the other hand, CNS diseases like AD have been associated with gliosis and impaired neurogenesis. Further, renin angiotensin system (RAS) is intricately associated with hypertension; however, the accumulating evidences suggest that over-activity of RAS may perpetuate the brain inflammation related with AD. Therefore, in the present study, we examined the effect of hypertension and RAS on glial (astrocytes and microglia) activation and hippocampal neurogenesis in a rat model of chronic hypertension...
September 7, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28881139/fracture-targeted-delivery-of-%C3%AE-catenin-agonists-via-peptide-functionalized-nanoparticles-augments-fracture-healing
#13
Yuchen Wang, Maureen R Newman, Marian Ackun-Farmmer, Michael P Baranello, Tzong-Jen Sheu, J Edward Puzas, Danielle S W Benoit
Despite several decades of progress, bone specific drug delivery is still a major challenge. Current bone-acting drugs require high-dose systemic administration which decreases therapeutic efficacy and increases off-target tissue effects. Here, a bone-targeted nanoparticle (NP) delivery system for a β-catenin agonist, 3-amino-6-(4-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-N-(pyridin-3-yl)pyrazine-2-carboxamide, a glycogen synthase kinase 3 beta (GSK-3β) inhibitor, was developed to enhance fracture healing...
September 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/28874700/contribution-of-c1485t-mutation-in-the-hbx-gene-to-human-and-murine-hepatocarcinogenesis
#14
Satoru Hagiwara, Naoshi Nishida, Ah-Mee Park, Yoriaki Komeda, Toshiharu Sakurai, Tomohiro Watanabe, Masatoshi Kudo
Although Hepatitis B virus (HBV) X gene mutations are frequently detected in HBV-related human hepatocellular carcinoma (HCC) patients, causative HBx mutations in the development of HCC have not yet been determined. We herein identified C1485T and C1653T mutations in the HBx gene as independent risk of HCC for HBV through the analysis using serum from chronic hepatitis B patients. We generated transgenic mice expressing wild-type (WT-HBxTg) and mutant (C1485T-HBxTg) HBx to assess the carcinogenic potential of mutated HBx...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873435/tgf-%C3%AE-signaling-is-an-effective-target-to-impair-survival-and-induce-apoptosis-of-human-cholangiocarcinoma-cells-a-study-on-human-primary-cell-cultures
#15
Anna Maria Lustri, Sabina Di Matteo, Alice Fraveto, Daniele Costantini, Alfredo Cantafora, Chiara Napoletano, Maria Consiglia Bragazzi, Felice Giuliante, Agostino M De Rose, Pasquale B Berloco, Gian Luca Grazi, Guido Carpino, Domenico Alvaro
Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT...
2017: PloS One
https://www.readbyqxmd.com/read/28867647/inhibitory-effects-of-melatonin-on-titanium-particle-induced-inflammatory-bone-resorption-and-osteoclastogenesis-via-suppression-of-nf-%C3%AE%C2%BAb-signaling
#16
Zichuan Ping, Zhirong Wang, Jiawei Shi, Liangliang Wang, Xiaobin Guo, Wei Zhou, Xuanyang Hu, Xiexing Wu, Yu Liu, Wen Zhang, Huilin Yang, Yaozeng Xu, Ye Gu, Dechun Geng
Wear debris-induced peri-implant osteolysis challenges the longevity of implants. The host response to wear debris causes chronic inflammation, promotes bone resorption, and impairs bone formation. We previously demonstrated that melatonin enhances bone formation and attenuates wear debris-induced bone loss in vivo. However, whether melatonin inhibits chronic inflammation and bone resorption at sites of wear debris-induced osteolysis remains unclear. In this study, we examined the potential inhibitory effects of melatonin on titanium particle-induced inflammatory osteolysis in a murine calvarial model and on RANKL-induced osteoclastic formation in bone marrow-derived macrophages...
August 31, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28858737/ginkgo-biloba-l-leaf-extract-offers-multiple-mechanisms-in-bridling-n-methylnitrosourea-mediated-experimental-colorectal-cancer
#17
Hanaa H Ahmed, Hanan S El-Abhar, Elsayed Abdul Khalik Hassanin, Noha F Abdelkader, Mohamed B Shalaby
In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12...
August 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28847007/homeostatic-control-of-metabolic-and-functional-fitness-of-treg-cells-by-lkb1-signalling
#18
Kai Yang, Daniel Bastardo Blanco, Geoffrey Neale, Peter Vogel, Julian Avila, Clary B Clish, Chuan Wu, Sharad Shrestha, Sherri Rankin, Lingyun Long, Anil Kc, Hongbo Chi
Regulatory T cells (Treg cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of Treg cells in the prevention of diverse types of inflammatory responses. It remains unclear how Treg cells orchestrate their homeostasis and interplay with environmental signals. Here we show that liver kinase B1 (LKB1) programs the metabolic and functional fitness of Treg cells in the control of immune tolerance and homeostasis...
August 31, 2017: Nature
https://www.readbyqxmd.com/read/28846104/berberine-binds-rxr%C3%AE-to-suppress-%C3%AE-catenin-signaling-in-colon-cancer-cells
#19
H Ruan, Y Y Zhan, J Hou, B Xu, B Chen, Y Tian, D Wu, Y Zhao, Y Zhang, X Chen, P Mi, L Zhang, S Zhang, X Wang, H Cao, W Zhang, H Wang, H Li, Y Su, X K Zhang, T Hu
Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα...
August 28, 2017: Oncogene
https://www.readbyqxmd.com/read/28844410/safety-tolerability-and-preliminary-efficacy-of-the-anti-fibrotic-small-molecule-pri-724-a-cbp-%C3%AE-catenin-inhibitor-in-patients-with-hepatitis-c-virus-related-cirrhosis-a-single-center-open-label-dose-escalation-phase-1-trial
#20
Kiminori Kimura, Akemi Ikoma, Maki Shibakawa, Shinji Shimoda, Kenichi Harada, Masanao Saio, Jun Imamura, Yosuke Osawa, Masamichi Kimura, Koji Nishikawa, Takuji Okusaka, Satoshi Morita, Kazuaki Inoue, Tatsuya Kanto, Koji Todaka, Yoichi Nakanishi, Michinori Kohara, Masashi Mizokami
BACKGROUND: There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. METHODS: In this single-center, open-label, phase 1 trial, we sequentially enrolled patients with HCV cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 was administered as a continuous intravenous infusion of 10, 40, or 160mg/m(2)/day for six cycles of 1week on and 1week off...
August 19, 2017: EBioMedicine
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