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https://www.readbyqxmd.com/read/28800359/the-selective-pi3k%C3%AE-inhibitor-byl719-as-a-novel-therapeutic-option-for-neuroendocrine-tumors-results-from-multiple-cell-line-models
#1
Svenja Nölting, Jakob Rentsch, Helma Freitag, Katharina Detjen, Franziska Briest, Markus Möbs, Victoria Weissmann, Britta Siegmund, Christoph J Auernhammer, Elke Tatjana Aristizabal Prada, Michael Lauseker, Ashley Grossman, Samantha Exner, Christian Fischer, Carsten Grötzinger, Jörg Schrader, Patricia Grabowski
BACKGROUND/AIMS: The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS: Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28800315/mir-99a-suppresses-proliferation-migration-and-invasion-of-esophageal-squamous-cell-carcinoma-cells-through-inhibiting-the-igf1r-signaling-pathway
#2
Li-Li Mei, Yun-Tan Qiu, Meng-Bing Huang, Wen-Jun Wang, Jie Bai, Zhi-Zhou Shi
miR-99a is down-regulated in esophageal squamous cell carcinoma (ESCC), however the role and underlying mechanism are still unknown. We aim to explore the role and mechanism of miR-99a down-regulation in ESCC. The expression of miR-99a in ESCC tissues and cell lines was detected by Human miRNA Microarrays and Real-time PCR. The effects of miR-99a on cell proliferation, migration and invasion were determined by Cell Counting Kit-8 (CCK-8) assay, transwell migration and invasion assay. Target gene of miR-99a were analyzed by target prediction software and validated by Real-time PCR and Western blotting assay...
July 31, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28795385/hsa_circ_0045714-regulates-chondrocyte-proliferation-apoptosis-and-extracellular-matrix-synthesis-by-promoting-the-expression-of-mir-193b-target-gene-igf1r
#3
Bao-Feng Li, Ying Zhang, Jin Xiao, Fei Wang, Mei Li, Xiao-Ze Guo, Hui-Bin Xie, Hong Xia, Bei Chen
In recent years, some studies have been made on the effects of circular RNA (circRNA) in osteoarthritis (OA) and so on; however, its mechanisms remain to be further explored. Studies have shown that tumor necrosis factor-alpha can inhibit hsa_circ_0045714 expression in chondrocytes so as to upregulate miR-193b expression. Dual-luciferase reporter assay showed that insulin-like growth factor 1 receptor (IGF1R) is a key target gene of miR-193b. Hsa_circ_0045714 over-expression does not influence miR-193b expression, but can inhibit its transcriptional activity, thereby upregulating IGF1R expression...
August 9, 2017: Human Cell
https://www.readbyqxmd.com/read/28793874/picropodophyllin-ppp-is-a-potent-rhabdomyosarcoma-growth-inhibitor-both-in-vitro-and-in-vivo
#4
Maciej Tarnowski, Marta Tkacz, Katarzyna Zgutka, Joanna Bujak, Patrycja Kopytko, Andrzej Pawlik
BACKGROUND: Insulin-like growth factors and insulin are important factors promoting cancer growth and metastasis. The molecules act through IGF1 (IGF1R) and insulin (InsR) receptors. Rhambodmyosarcomas (RMS) overproduce IGF2 - a potent ligand for IGF1R and, at the same time, highly express IGF1 receptor. The purpose of the study was to evaluate possible application of picropodophyllin (PPP) - a potent IGF1R inhibitor. METHODS: In our study we used a number of in vitro assays showing influence of IGF1R blockage on RMS cell lines (both ARMS and ERMS) proliferation, migration, adhesion, cell cycling and signal transduction pathways...
August 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28790184/adiponectin-protects-against-development-of-metabolic-disturbances-in-a-pcos-mouse-model
#5
Anna Benrick, Belén Chanclón, Peter Micallef, Yanling Wu, Laila Hadi, John M Shelton, Elisabet Stener-Victorin, Ingrid Wernstedt Asterholm
Adiponectin, together with adipocyte size, is the strongest factor associated with insulin resistance in women with polycystic ovary syndrome (PCOS). This study investigates the causal relationship between adiponectin levels and metabolic and reproductive functions in PCOS. Prepubertal mice overexpressing adiponectin from adipose tissue (APNtg), adiponectin knockouts (APNko), and their wild-type (WT) littermate mice were continuously exposed to placebo or dihydrotestosterone (DHT) to induce PCOS-like traits...
August 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28780099/effect-of-recombinant-bovine-somatotropin-on-leukocyte-mrna-expression-for-genes-related-to-cell-energy-metabolism-cytokine-production-phagocytosis-oxidative-burst-and-adaptive-immunity
#6
P R B Silva, C D Nelson, J P Driver, W W Thatcher, R C Chebel
Objectives of the current experiment were to evaluate the effects of treatment of periparturient dairy cows with recombinant bovine somatotropin (rbST) on mRNA expression in peripheral leukocytes for genes related to the somatotropic axis, cell energy metabolism, and innate and adaptive immune responses. Cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to an untreated control group (n = 98) or to receive 125 mg of rbST weekly from -21 to 21 d relative to calving (rbST125; n = 98)...
August 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28768959/next-generation-sequencing-based-mutation-screening-of-86-patients-with-idiopathic-short-stature
#7
Atsushi Hattori, Yuko Katoh-Fukui, Akie Nakamura, Keiko Matsubara, Tsutomu Kamimaki, Hiroyuki Tanaka, Sumito Dateki, Masanori Adachi, Koji Muroya, Shinobu Yoshida, Shinobu Ida, Marie Mitani, Keisuke Nagasaki, Tsutomu Ogata, Erina Suzuki, Kenichiro Hata, Kazuhiko Nakabayashi, Yoichi Matsubara, Satoshi Narumi, Toshiaki Tanaka, Maki Fukami
Although mutations in ACAN, FGFR3, NPR2, and SHOX typically lead to skeletal dysplasia, and mutations in GHRHR, GH1, GHR, STAT5B, IGF1, IGFALS, and IGF1R usually underlie hormonal defects of the growth hormone (GH)-insulin-like growth factor 1 (IGF1) axis, such mutations have also been identified in patients with idiopathic short stature (ISS). Of these, SHOX abnormalities are known to account for a certain percentage of ISS cases, whereas the frequency of mutations in the other 10 genes in ISS cohorts remains unknown...
August 3, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28768911/a-ccr2-myeloid-cell-niche-required-for-pancreatic-%C3%AE-cell-growth
#8
Kristin Mussar, Stephanie Pardike, Tobias M Hohl, Gary Hardiman, Vincenzo Cirulli, Laura Crisa
Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1+ and CCR2+ macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28766847/expression-of-insulin-like-growth-factor-1-receptor-in-circulating-tumor-cells-of-patients-with-breast-cancer-is-associated-with-patient-outcomes
#9
Maria Spiliotaki, Dimitris Mavroudis, Maria Kokotsaki, Eleni-Kyriaki Vetsika, Ioannis Stoupis, Alexios Matikas, Galatea Kallergi, Vassilis Georgoulias, Sofia Agelaki
In patients with breast cancer, markers of aggressiveness such as dysregulation of the insulin-like growth factor receptor (IGF1R) system and E-cadherin loss are commonly observed. Reduced IGF1R expression is correlated with decreased E-cadherin levels and increased cell motility. We assessed IGF1R and E-cadherin expression in circulating tumor cells (CTCs) in breast cancer patients. Peripheral blood mononuclear cells of early (n=87) and metastatic (n=126) stage breast cancer patients (obtained prior to adjuvant and first-line chemotherapy) were evaluated using double immunofluorescence (IF) staining for cytokeratin (CK) and IGF1R...
August 2, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28758253/mir-182-selectively-targets-hoxa10-in-goat-endometrial-epithelium-cells-in-vitro
#10
L Zhang, X-R Liu, J-Z Liu, Y-X Song, Z-Q Zhou, B-Y Cao
Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo...
July 30, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28757453/lnc133b-a-novel-long-non-coding-rna-regulates-bovine-skeletal-muscle-satellite-cell-proliferation-and-differentiation-by-mediating-mir-133b
#11
Cong Fei Jin, Yan Li, Xiang Bin Ding, Xin Li, Lin Lin Zhang, Xin Feng Liu, Hong Guo
The proliferation and differentiation of skeletal muscle satellite cells is regulated by multiple regulatory factors including non-coding RNAs. It has been reported that miR-133b regulates myogenesis. In this study, we detected a novel lncRNA, lnc133b, which is completely complemented by mature miR-133b, indicating that lnc133b may regulate the expression of miR-133b by "sponge" miR-133b. A luciferase report assay confirmed that lnc133b interacts with miR-133b in regions complemented by miR-133b. We successfully constructed lnc133b gain/loss-of-function cell models by infecting LV-1nc133b and transfecting si-lnc133b into satellite cells...
July 27, 2017: Gene
https://www.readbyqxmd.com/read/28757207/focal-adhesion-and-igf1r-dependent-survival-and-migratory-pathways-mediate-tumor-resistance-to-mtorc1-2-inhibition
#12
Sang-Oh Yoon, Sejeong Shin, Florian A Karreth, Gwen R Buel, Mark P Jedrychowski, David R Plas, Shoukat Dedhar, Steven P Gygi, Philippe P Roux, Noah Dephoure, John Blenis
Aberrant signaling by the mammalian target of rapamycin (mTOR) contributes to the devastating features of cancer cells. Thus, mTOR is a critical therapeutic target and catalytic inhibitors are being investigated as anti-cancer drugs. Although mTOR inhibitors initially block cell proliferation, cell viability and migration in some cancer cells are quickly restored. Despite sustained inhibition of mTORC1/2 signaling, Akt, a kinase regulating cell survival and migration, regains phosphorylation at its regulatory sites...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28756492/large-scale-comprehensive-immunohistochemical-biomarker-analyses-in-esophageal-squamous-cell-carcinoma
#13
Ken Hatogai, Satoshi Fujii, Takashi Kojima, Hiroyuki Daiko, Shogo Nomura, Toshihiko Doi, Shigehisa Kitano, Atsushi Ohtsu, Yuichi Takiguchi, Takayuki Yoshino, Atsushi Ochiai
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a heterogeneous disease in the sense that the biological behavior is regulated by the activation of various signaling pathways. The aim of this study was to investigate the relationships between the expressions of various targetable proteins and the clinicopathological characteristics of ESCC patients. METHODS: A total of 286 patients with ESCC who had undergone curative surgical resection without neoadjuvant therapy were enrolled in this study...
July 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28754845/shuanghuang-shengbai-granule-cures-myelosuppression-and-suppresses-lung-cancer-progression-mechanism-and-therapeutic-targets-from-the-aspect-of-micrornas
#14
Shuang Wang, Zhenye Xu, Lifang Wang
BACKGROUND: Shuanghuang Shengbai granule is effective in curing cyclophosphamide-induced myelosuppression without promoting lung cancer development. This study aims to investigate its mechanism and therapeutic targets. METHODS: Nude mice with lung cancer were treated with physiological saline (control), cyclophosphamide, or cyclophosphamide + Shuanghuang Shengbai. MicroRNA microarray was used to investigate the differentially expressed microRNAs in lung cancer stem cells or bone marrow hematopoietic stem cells between the three groups...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754794/a-comparative-study-on-the-wcrf-international-university-of-bristol-methodology-for-systematic-reviews-of-mechanisms-underpinning-exposure-cancer-associations
#15
Gökhan Ertaylan, Charlotte Le Cornet, Eline H van Roekel, Audrey Y Jung, Martijn J L Bours, Antje Damms-Machado, Piet A van den Brandt, Helena Schock, Theo M de Kok, Jan Theys, Ilja C W Arts, Rudolf Kaaks, Matty P Weijenberg, Renée Turzanski Fortner
The World Cancer Research Fund International and the University of Bristol have developed a novel framework for providing an overview of mechanistic pathways and conducting a systematic literature review of the biologically plausible mechanisms underlying exposure-cancer associations. Two teams independently applied the two-stage framework on mechanisms underpinning the association between body fatness and breast cancer to test the framework feasibility and reproducibility as part of a WCRF-Commissioned validation study...
July 28, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28751539/mechanisms-of-resistance-to-ntrk-inhibitors-and-therapeutic-strategies-in-ntrk1-rearranged-cancers
#16
Miho J Fuse, Koutaroh Okada, Tomoko Oh-Hara, Hayato Ogura, Naoya Fujita, Ryohei Katayama
Neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangement leads to constitutive activation of NTRK1, which induces high transforming ability. NTRK-rearranged cancers have been identified in several cancer types, such as glioblastoma, non-small-cell lung cancer, and colorectal cancer. Although there are currently no clinically approved inhibitors that target NTRK1, several tyrosine kinase inhibitors (TKIs), such as entrectinib and LOXO-101, are in clinical trials. The purpose of this study was to identify potential mechanisms of resistance to NTRK inhibitors and find potential therapeutic strategies to overcome the resistance...
July 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#17
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28742836/the-impact-of-met-igf-1-igf1r-expression-and-egfr-mutations-on-survival-of-patients-with-non-small-cell-lung-cancer
#18
Samer Al-Saad, Elin Richardsen, Thomas K Kilvaer, Tom Donnem, Sigve Andersen, Mehrdad Khanehkenari, Roy M Bremnes, Lill-Tove Busund
INTRODUCTION: To compare the efficacy of silver in situ hybridization (SISH) and immunohistochemistry (IHC) in detecting MET and IGF1R alterations and to investigate their prevalence and prognostic significance. A possible correlation between MET receptor expression, MET gene alterations and the two most frequent occurring EGFR gene mutations was also investigated. MATERIALS AND METHODS: Stage I to IIIA tumors from 326 patients with NSCLC were immunohistochemically tested for protein expression of MET and IGF-1...
2017: PloS One
https://www.readbyqxmd.com/read/28740455/insulin-like-growth-factor-1-receptor-expression-in-advanced-non-small-cell-lung-cancer-and-its-impact-on-overall-survival
#19
Mojca Humar, Izidor Kern, Gregor Vlacic, Vedran Hadzic, Tanja Cufer
BACKGROUND: The insulin-like growth factor 1 receptor (IGF1R) expression has been addressed as a potential prognostic marker in non-small-cell lung cancer (NSCLC) in various studies; however, the associations between IGF1R expression and prognosis of advanced NSCLC patients is still controversial. The aim of our observational, cohort study was to evaluate the expression of IGF1R in advanced NSCLC and its prognostic role. A subgroup analysis was performed to address the influence of pre-existing type 2 diabetes mellitus (T2DM) status on IGF1R expression and overall survival (OS)...
June 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28739729/the-axis-of-cxcr4-sdf-1-plays-a-role-in-colon-cancer-cell-adhesion-through-regulation-of-the-akt-and-igf1r-signalling-pathways
#20
Fei Zheng, Zhongtao Zhang, Valentina Flamini, Wen G Jiang, Yuxin Cui
BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer in the world. The high mortality of this tumor is mainly due to its invasive properties, as it forms metastases in multiple organs, preferentially in the liver. There has evidence showing that C-X-C chemokine receptor type 4 (CXCR-4) and its ligand, stromal cell-derived factor-1 (SDF-1), plays an important role in cancer progression and metastasis. However, the molecular mechanism underling the CRCR4-mediated CRC metastasis has not been well characterized...
August 2017: Anticancer Research
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