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https://www.readbyqxmd.com/read/28801734/fibrinogen-promotes-malignant-biological-tumor-behavior-involving-epithelial-mesenchymal-transition-via-the-p-akt-p-mtor-pathway-in-esophageal-squamous-cell-carcinoma
#1
Fei Zhang, Yun Wang, Peng Sun, Zhi-Qiang Wang, De-Shen Wang, Dong-Sheng Zhang, Feng-Hua Wang, Jian-Hua Fu, Rui-Hua Xu, Yu-Hong Li
PURPOSE: Hyperfibrinogenemia is associated with unfavorable prognosis and advanced tumor behavior in various malignancies, including esophageal squamous cell carcinoma (ESCC). However, its biological function in ESCC is unknown. The present study was designed to further validate the prognostic value of preoperative plasma hyperfibrinogenemia and evaluate the biological role of fibrinogen, as well as the underlying mechanism in ESCC. METHODS: Data from 452 cases with newly diagnosed ESCC followed by curative surgery between 2006 and 2010 were retrospectively evaluated...
August 11, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28794477/up-regulation-of-brca1-associated-ring-domain-1-promotes-hepatocellular-carcinoma-progression-by-targeting-akt-signaling
#2
Yan Liao, Shengguang Yuan, Xinhuang Chen, Pengpeng Zhu, Jun Li, Liling Qin, Weijia Liao
The present study was designed to investigate the potential clinical, pathological, prognostic value, role and mechanism of BRCA1-associated RING Domain 1 (BARD1) in Hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry were performed to evaluate the expression of BARD1 mRNA and protein. The expression of BARD1 in the HCC tissue samples was markedly higher than that in the adjacent noncancerous liver tissues. Elevated BARD1 expression was positively correlated with tumor-node-metastasis stage, Barcelona-Clinic Liver Cancer stage, hepatitis B surface antigen, large tumor size, serum alpha-fetoprotein levels, and serum aspartate aminotransferase levels...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789624/hedgehog-inhibitor-sonidegib-potentiates-177-lu-octreotate-therapy-of-got1-human-small-intestine-neuroendocrine-tumors-in-nude-mice
#3
Johan Spetz, Britta Langen, Nils Rudqvist, Toshima Z Parris, Khalil Helou, Ola Nilsson, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-octreotate can be used to treat somatostatin receptor expressing neuroendocrine tumors. It is highly effective in animal models, but clinical studies have so far only demonstrated low cure rates. Hedgehog inhibitors have shown therapeutic effect as monotherapy in neuroendocrine tumor model systems and might be one option to enhance the efficacy of (177)Lu-octreotate therapy. The aim of this study was to determine the therapeutic effect of combination therapy using (177)Lu-octreotate and the Hedgehog signaling pathway inhibitor sonidegib...
August 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28782620/anti-inflammatory-effect-of-cortex-eucommiae-via-modulation-of-the-toll-like-receptor-4-pathway-in-lipopolysaccharide-stimulated-raw-264-7-macrophages
#4
Wonil Koh, Joon-Shik Shin, Jinho Lee, In-Hee Lee, Sang Kook Lee, In-Hyuk Ha, Hwa-Jin Chung
ETHNOPHARMOCOLOGICAL RELEVANCE: Cortex Eucommiae (CE), the bark of Eucommia ulmoides Oliv., has been traditionally used for its kidney-tonifying and bone- and tendon-enhancing properties in Korea, China, and Japan. CE has been historically prescribed for inflammatory conditions such as arthritis of the knee and ankle. AIM OF THE STUDY: Although CE has recently been shown to suppress inflammation in scientific studies, whether this effect involves modulation of the toll-like receptor 4 (TLR-4) pathway is currently unknown...
August 3, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28777148/new-mechanisms-of-mtor-pathway-activation-in-kit-mutant-malignant-gists
#5
Jerzy Lasota, Artur Kowalik, Anna Felisiak-Golabek, Sebastian Zięba, Zeng-Feng Wang, Markku Miettinen
A great majority of gastrointestinal stromal tumors (GISTs) are primarily driven by gain-of-function KIT receptor tyrosine kinase mutations that subsequently lead to activation of phosphatidiylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway, a downstream effector of KIT signaling. KIT tyrosine kinase inhibitor, imatinib mesylate, has been successfully used for the treatment of primary, advanced, and disseminated GISTs. Recently, activation of mTOR pathway independent of KIT signaling was demonstrated in imatinib mesylate naïve malignant GISTs and treatment-resistant metastatic tumors...
August 2, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28772167/glycogen-synthase-kinase-3-inhibition-sensitizes-human-induced-pluripotent-stem-cells-to-thiol-containing-antioxidants-induced-apoptosis
#6
Chengyi Tu, Robert Xu, Meghana Koleti, Janet Zoldan
Inhibition of glycogen synthase kinase 3 (GSK3) is an extensively used strategy to activate Wnt pathway for pluripotent stem cell (PSC) differentiation. However, the effects of such inhibition on PSCs, besides upregulating the Wnt pathway, have rarely been investigated despite that GSK3 is broadly involved in other cellular activities such as insulin signaling and cell growth/survival regulation. Here we describe a previously unknown synergistic effect between GSK3 inhibition (e.g., Chir99021 and LY2090314) and various normally non-toxic thiol-containing antioxidants (e...
July 22, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28768913/hiv-1-selectively-targets-gut-homing-ccr6-cd4-t-cells-via-mtor-dependent-mechanisms
#7
Delphine Planas, Yuwei Zhang, Patricia Monteiro, Jean-Philippe Goulet, Annie Gosselin, Nathalie Grandvaux, Thomas J Hope, Ariberto Fassati, Jean-Pierre Routy, Petronela Ancuta
Gut-associated lymphoid tissues are enriched in CCR6+ Th17-polarized CD4+ T cells that contribute to HIV-1 persistence during antiretroviral therapy (ART). This raises the need for Th17-targeted immunotherapies. In an effort to identify mechanisms governing HIV-1 permissiveness/persistence in gut-homing Th17 cells, we analyzed the transcriptome of CCR6+ versus CCR6- T cells exposed to the gut-homing inducer retinoic acid (RA) and performed functional validations in colon biopsies of HIV-infected individuals receiving ART (HIV+ART)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28746938/magnolol-inhibits-the-growth-of-non-small-cell-lung-cancer-via-inhibiting-microtubule-polymerization
#8
Jia Shen, Hailin Ma, Tiancheng Zhang, Hui Liu, Linghua Yu, Guosheng Li, Huishuang Li, Meichun Hu
BACKGROUND: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. METHODS: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata) on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC) cells...
July 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28732797/functional-convergence-of-akt-protein-with-vegfr-1-in-human-endothelial-progenitor-cells-exposed-to-sera-from-patient-with-type-2-diabetes-mellitus
#9
Mehdi Hassanpour, Aysa Rezabakhsh, Reza Rahbarghazi, Alireza Nourazarian, Mohammad Nouri, Çığır Biray Avci, Shahrooz Ghaderi, Neda Alidadyani, Bakiye Goker Bagca, Hesam Saghaei Bagheri
Diabetes mellitus type 2 predisposes patients to various microvascular complications. In the current experiment, the potent role of diabetes mellitus was investigated on the content of VEGFR-1, -2, Tie-1 and -2, and Akt in human endothelial progenitor cells. The gene expression profile of mTOR and Hedgehog signaling pathways were measured by PCR array. The possible crosstalk between RTKs, mTOR and Hedgehog signaling was also studied by bioinformatic analysis. Endothelial progenitor cells were incubated with serum from normal and diabetic for 7days...
July 18, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#10
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723628/ese-1-elf3-mrna-expression-associates-with-poor-survival-outcomes-in-her2-breast-cancer-patients-and-is-critical-for-tumorigenesis-in-her2-breast-cancer-cells
#11
Adwitiya Kar, Arthur Gutierrez-Hartmann
ESE-1/Elf3 and HER2 appear to establish a positive feedback regulatory loop, but the precise role of ESE-1 in HER2+ breast tumorigenesis remains unknown. Analyzing public repositories, we found that luminal B and HER2 subtype patients with high ESE-1 mRNA levels displayed worse relapse free survival. We stably knocked down ESE-1 in HER2+ luminal B BT474 cells and HER2 subtype SKBR3 cells, which resulted in decreased cell proliferation, colony formation, and anchorage-independent growth in vitro. Stable ESE-1 knockdown inhibited HER2-dependent signaling in BT474 cells and inhibited mTOR activation in SKBR3 cells, but reduced Akt signaling in both cell types...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28712664/gsk3-and-its-interactions-with-the-pi3k-akt-mtor-signalling-network
#12
REVIEW
Miguel A Hermida, J Dinesh Kumar, Nick R Leslie
Glycogen Synthase Kinase-3 (GSK3 or GSK-3) is a promiscuous protein kinase and its phosphorylation of its diverse substrates has major influences on many areas of physiology and pathology, including cellular metabolism, lineage commitment and neuroscience. GSK3 was one of the first identified substrates of the heavily studied oncogenic kinase AKT, phosphorylation by which inhibits GSK3 activity via the formation of an autoinhibitory pseudosubstrate sequence. This has led to investigation of the role of GSK3 inhibition as a key component of the cellular responses to growth factors and insulin, which stimulate the class I PI 3-Kinases and in turn AKT activity and GSK3 phosphorylation...
June 27, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28706145/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#13
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Sigillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700668/conditional-cell-reprogramming-involves-non-canonical-%C3%AE-catenin-activation-and-mtor-mediated-inactivation-of-akt
#14
Frank A Suprynowicz, Christopher M Kamonjoh, Ewa Krawczyk, Seema Agarwal, Anton Wellstein, Fadeke A Agboke, Sujata Choudhury, Xuefeng Liu, Richard Schlegel
The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-267362, converts primary epithelial cells growing in vitro into an undifferentiated adult stem cell-like state that is characterized by long-term proliferation. This cell culture method also maintains the proliferation of adult epithelial stem cells from various tissues. Both primary and adult stem cells retain their tissue-specific differentiation potential upon removal of the culture conditions. Due to the ability to modulate the proliferation and differentiation of the cells, this method is referred to as conditional reprogramming and it is increasingly being used in studies of tumor heterogeneity, personalized medicine and regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28687354/aspirin-disrupts-the-mtor-raptor-complex-and-potentiates-the-anti-cancer-activities-of-sorafenib-via-mtorc1-inhibition
#15
Danni Sun, Hongchun Liu, Xiaoyang Dai, Xingling Zheng, Juan Yan, Rongrui Wei, Xuhong Fu, Min Huang, Aijun Shen, Xun Huang, Jian Ding, Meiyu Geng
Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners...
July 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28683304/inhibition-of-the-schizophrenia-associated-microrna-mir-137-disrupts-nrg1%C3%AE-neurodevelopmental-signal-transduction
#16
Kristen Therese Thomas, Bart Russell Anderson, Niraj Shah, Stephanie Elaine Zimmer, Daniel Hawkins, Arielle Nicole Valdez, Qiaochu Gu, Gary Jonathan Bassell
Genomic studies have repeatedly associated variants in the gene encoding the microRNA miR-137 with increased schizophrenia risk. Bioinformatic predictions suggest that miR-137 regulates schizophrenia-associated signaling pathways critical to neural development, but these predictions remain largely unvalidated. In the present study, we demonstrate that miR-137 regulates neuronal levels of p55γ, PTEN, Akt2, GSK3β, mTOR, and rictor. All are key proteins within the PI3K-Akt-mTOR pathway and act downstream of neuregulin (Nrg)/ErbB and BDNF signaling...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28664915/kinase-driven-metabolic-signalling-as-a-predictor-of-response-to-carboplatin-paclitaxel-adjuvant-treatment-in-advanced-ovarian-cancers
#17
Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K Alex Hodge, David S Alberts, Jose M Guillen-Rodriguez, Ting Dong, Maurizio Memo, Franco Odicino, Roberto Angioli, Lance A Liotta, Sergio L Pecorelli, Emanuel F Petricoin, Mariaelena Pierobon
BACKGROUND: The biological mechanisms underlying early- and advanced-stage epithelial ovarian cancers (EOCs) are still poorly understood. This study explored kinase-driven metabolic signalling in early and advanced EOCs, and its role in tumour progression and response to carboplatin-paclitaxel treatment. METHODS: Tumour epithelia were isolated from two independent sets of primary EOC (n=72 and 30 for the discovery and the validation sets, respectively) via laser capture microdissection...
August 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28650474/an-activating-mutation-of-gnb1-is-associated-with-resistance-to-tyrosine-kinase-inhibitors-in-etv6-abl1-positive-leukemia
#18
O Zimmermannova, E Doktorova, J Stuchly, V Kanderova, D Kuzilkova, H Strnad, J Starkova, M Alberich-Jorda, J H F Falkenburg, J Trka, J Petrak, J Zuna, M Zaliova
Leukemias harboring the ETV6-ABL1 fusion represent a rare subset of hematological malignancies with unfavorable outcomes. The constitutively active chimeric Etv6-Abl1 tyrosine kinase can be specifically inhibited by tyrosine kinase inhibitors (TKIs). Although TKIs represent an important therapeutic tool, so far, the mechanism underlying the potential TKI resistance in ETV6-ABL1-positive malignancies has not been studied in detail. To address this issue, we established a TKI-resistant ETV6-ABL1-positive leukemic cell line through long-term exposure to imatinib...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28594907/gastrointestinal-cancer-cells-treatment-with-bevacizumab-activates-a-vegf-autoregulatory-mechanism-involving-telomerase-catalytic-subunit-htert-via-pi3k-akt-hif-1%C3%AE-and-vegf-receptors
#19
Nadine Mahfouz, Roula Tahtouh, Nada Alaaeddine, Joelle El Hajj, Riad Sarkis, Ray Hachem, Issam Raad, George Hilal
BACKGROUND: Targeting angiogenesis has been considered a promising treatment of choice for a large number of malignancies, including gastrointestinal cancers. Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) being used for this purpose. However, treatment efficacy is largely questioned. Telomerase activity, responsible for cancer cell immortality, is detected in 85-95% of human cancers and is considered a potential regulator of VEGF. The aim of our study was to investigate the interrelationship between VEGF and hTERT in gastrointestinal cancers and to explore cell response to a combined inhibition of telomerase and VEGF...
2017: PloS One
https://www.readbyqxmd.com/read/28593618/rig-i-a-multifunctional-protein-beyond-a-pattern-recognition-receptor
#20
REVIEW
Xiao-Xiao Xu, Han Wan, Li Nie, Tong Shao, Li-Xin Xiang, Jian-Zhong Shao
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations...
June 8, 2017: Protein & Cell
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