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https://www.readbyqxmd.com/read/28448670/molecular-mechanisms-underlying-the-filtration-bleb-maintaining-effects-of-suberoylanilide-hydroxamic-acid-saha
#1
Akiko Futakuchi, Toshihiro Inoue, Tomokazu Fujimoto, Utako Kuroda, Miyuki Inoue-Mochita, Eri Takahashi, Saori Ohira, Hidenobu Tanihara
Purpose: Suberoylanilide hydroxamic acid (SAHA) has been shown to support the maintenance of experimental filtration blebs in animal models. This study was performed to investigate the molecular mechanisms underlying the bleb-maintaining effects of SAHA in modulating wound healing activities of conjunctival fibroblasts. Methods: Human conjunctival fibroblasts (HConFs) were pretreated with SAHA before treatment with TGF-β2. Microarray-based screening was used to investigate the gene expression profiles...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28448439/ykl-40-induced-inhibition-of-mir-590-3p-promotes-interleukin-18-expression-and-angiogenesis-of-endothelial-progenitor-cells
#2
Te-Mao Li, Shan-Chi Liu, Ya-Hsin Huang, Chien-Chung Huang, Chin-Jung Hsu, Chun-Hao Tsai, Shih-Wei Wang, Chih-Hsin Tang
YKL-40, also known as human cartilage glycoprotein-39 or chitinase-3-like-1, is a pro-inflammatory protein that is highly expressed in rheumatoid arthritis (RA) patients. Angiogenesis is a critical step in the pathogenesis of RA, promoting the infiltration of inflammatory cells into joints and providing oxygen and nutrients to RA pannus. In this study, we examined the effects of YKL-40 in the production of the pro-inflammatory cytokine interleukin-18 (IL-18), and the stimulation of angiogenesis and accumulation of osteoblasts...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28448438/antiplatelet-activity-of-a-newly-synthesized-novel-ruthenium-ii-a-potential-role-for-akt-jnk-signaling
#3
Themmila Khamrang, Kuo-Chen Hung, Chih-Hsuan Hsia, Cheng-Ying Hsieh, Marappan Velusamy, Thanasekaran Jayakumar, Joen-Rong Sheu
In oncotherapy, ruthenium complexes are considered as potential alternatives for platinum compounds, and have been proved as promising anticancer drugs with high efficacy and lesser side effects. Platelet activation plays a major role in cancer metastasis and progression. Hence, this study explored the effect of a newly synthesized ruthenium complex, [Ru(η⁶-cymene)(L)Cl]BF₄(TQ5), where L = 4-phenyl-2-pyridin-2-yl-quinazoline), on human platelet activation. TQ5 (3-5 µM) inhibited concentration-dependent collagen-induced platelet aggregation in washed human platelets...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28448171/novel-investigational-drugs-active-as-single-agents-in-multiple-myeloma
#4
Mattia D'Agostino, Marco Salvini, Antonio Palumbo, Alessandra Larocca, Francesca Gay
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. Patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies...
April 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28447797/signal-transductions-of-beas-2b-cells-in-response-to-carcinogenic-pm2-5-exposure-based-on-microfluidic-system
#5
Lulu Zheng, Sixiu Liu, Guoshun Zhuang, Jian Xu, Qi Liu, Xinlian Zhang, Congrui Deng, Zhigang Guo, Wang Zhao, Tingna Liu, Yiqi Wang, Yuxiao Zhang, Jing Lin, Qiongzhen Wang, Guodong Sui
PM2.5 (particulate matter less than 2.5 micrometers in diameter) is considered as a harmful carcinogen. Determining the precise relationship between the chemical constituents of PM2.5 in the air and cancer progression could aid the treatment of environment related disease and establishing risk reduction strategies. Herein, we used transcriptomics (RNA-seq) and integrated microfluidic system to identify the global gene expression and differential target proteins expression induced by ambient fine particles collected from the heavy haze in China...
April 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28447761/mir-21-inhibitor-suppresses-cell-proliferation-and-colony-formation-through-regulating-the-pten-akt-pathway-and-improves-paclitaxel-sensitivity-in-cervical-cancer-cells
#6
Guohui Du, Dongmei Cao, Lingzheng Meng
The present study aimed to investigate the role and the molecular mechanisms underlying the effects of microRNA-21 (miR-21) on the proliferation, apoptosis and colony formation of cervical cancer cells, and to examine the role of miR-21 in mediating the sensitivity of cervical cancer cells to paclitaxel (PTX). Reverse transcription‑quantitative polymerase chain reaction was employed to determine the level of miR‑21 in various cervical cancer and normal cervical cells. The results revealed that the expression levels of miR-21 in cervical cancer cells were markedly higher when compared with normal cervical cells...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447730/pioglitazone-ameliorates-a%C3%AE-42-deposition-in-rats-with-diet-induced-insulin-resistance-associated-with-akt-gsk3%C3%AE-activation
#7
Sisi Yang, Zhe Chen, Ming Cao, Renjie Li, Zhigang Wang, Muxun Zhang
Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447723/upregulation-of-rasal2-promotes-proliferation-and-metastasis-and-is-targeted-by-mir-203-in-hepatocellular-carcinoma
#8
Jian-Feng Fang, Hai-Ping Zhao, Zheng-Fei Wang, Shu-Sen Zheng
RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in various types of cancer. It has previously been demonstrated that RASAL2 is hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern of RASAL2 and its potential role in HCC remain to be elucidated. The present study demonstrated that the expression of RASAL2 was upregulated in HCC tissues, compared with in normal liver tissues, by using immunohistochemistry. In addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of RASAL2 inhibited the growth and invasion of HCC cells...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447311/attenuation-of-glutamate-induced-excitotoxicity-by-withanolide-a-in-neuron-like-cells-role-for-pi3k-akt-mapk-signaling-pathway
#9
Nawab John Dar, Naresh Kumar Satti, Prabhu Dutt, Abid Hamid, Muzamil Ahmad
Glutamate-induced excitotoxicity is one of the major underlying mechanisms for neurodegenerative diseases. Efforts are being made to treat such conditions with an array of natural compounds that can modulate the release of glutamate or the underlying mechanisms associated with it. Withania somnifera extract has potent pharmacologic activity similar to that of Korean Ginseng tea and is used to treat several neuronal disorders. However, to date, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders...
April 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28447038/dermal-white-adipose-tissue-renewal-is-regulated-by-the-pdgfa-akt-axis
#10
EDITORIAL
Giuseppe Cappellano, Christian Ploner
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#11
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446728/inhibition-of-hsf1-suppresses-the-growth-of-hepatocarcinoma-cell-lines-in-vitro-and-akt-driven-hepatocarcinogenesis-in-mice
#12
Antonio Cigliano, Chunmei Wang, Maria G Pilo, Marta Szydlowska, Stefania Brozzetti, Gavinella Latte, Giovanni M Pes, Rosa M Pascale, Maria A Seddaiu, Gianpaolo Vidili, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F Calvisi
Upregulation of the heat shock transcription factor 1 (HSF1) has been described as a frequent event in many cancer types, but its oncogenic role in hepatocellular carcinoma (HCC) remains poorly delineated. In the present study, we assessed the function(s) of HSF1 in hepatocarcinogenesis via in vitro and in vivo approaches. In particular, we determined the importance of HSF1 on v-Akt murine thymoma viral oncogene homolog (AKT)-induced liver cancer development in mice. We found that knockdown of HSF1 activity via specific siRNA triggered growth restraint by suppressing cell proliferation and inducing massive cell apoptosis in human HCC cell lines...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446718/baicalein-inhibits-pancreatic-cancer-cell-proliferation-and-invasion-via-suppression-of-nedd9-expression-and-its-downstream-akt-and-erk-signaling-pathways
#13
Rong-Tao Zhou, Mei He, Ze Yu, Yang Liang, Yuzhe Nie, Sheng Tai, Chun-Bo Teng
Baicalein, a flavone ingredient of Scutellaria baicalensis Georgi, is a promising anti-cancer agent. However, its potential anti-pancreatic cancer effects and the underlying mechanisms are still unclear. In this study, we showed that Baicalein not only induced apoptosis, but also suppressed proliferation, migration and invasion of two pancreatic cancer cell lines BxPC-3 and PANC-1 in a dose- and time-dependent manner. Notably, Baicalein exhibited low toxicity to normal human liver or kidney cells. We further discovered that Baicalein suppressed BxPC-3 and PANC-1 cell proliferation and invasion through targeting the expression of NEDD9, a Cas scaffolding protein, to decrease Akt and ERK activities...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446642/co-targeting-mtorc-and-egfr-signaling-as-a-therapeutic-strategy-in-hnscc
#14
Adam D Swick, Prashanth J Prabakaran, Margot C Miller, Amal M Javaid, Michael M Fisher, Emmanuel Sampene, Irene M Ong, Rong Hu, Mari Iida, Kwangok P Nickel, Justine Y Bruce, Deric L Wheeler, Randall J Kimple
Head and neck squamous cell carcinomas (HNSCCs) are frequently altered along the PI3K/AKT/mTORC signaling axis. Despite excellent preclinical data, the use of compounds targeting this pathway as monotherapy has been underwhelming in initial clinical trials and identification of predictive biomarkers remains challenging. To investigate mTORC specific inhibition we tested catalytic mTORC (AZD8055) and PI3K/mTORC (NVP-BEZ-235) inhibitors +/- cetuximab in a panel of HNSCC cell lines and patient derived xenografts (PDX)...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28446508/enrichment-of-pik3-akt-mtor-pathway-activation-in-hepatic-metastases-from-breast-cancer
#15
Mariaelena Pierobon, Corrine Ramos, Shukmei Wong, K Alex Hodge, Jessica Aldrich, Sara A Byron, Stephen P Anthony, Nicholas J Robert, Donald W Northfelt, Mohammad Jahanzeb, Linda Vocila, Julia D Wulfkuhle, Guido Gambara, Rosa Isela Gallagher, Bryant Dunetz, Nicholas Hoke, Ting Dong, David W Craig, Massimo Cristofanilli, Brian Leyland Jones, Lance Liotta, Joyce A O'Shaughnessy, John D Carpten, Emanuel F Petricoin
Purpose: Little is known about the molecular signatures associated with specific metastatic sites in breast cancer. Using comprehensive multi-omic molecular profiling, we assessed whether alterations or activation of the PI3K-AKT-mTOR pathway is associated with specific sites of breast cancer metastasis. <p>Experimental Design: NGS-based whole exome sequencing was coupled with Reverse Phase Protein Microarray (RPPA) functional signaling network analysis to explore the PI3K-AKT-mTOR axis in 32 pretreated breast cancer metastases...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446504/feasibility-of-ultra-high-throughput-functional-screening-of-melanoma-biopsies-for-discovery-of-novel-cancer-drug-combinations
#16
Adam A Friedman, Yun Xia, Lorenzo Trippa, Long P Le, Vivien Igras, Dennie T Frederick, Jennifer A Wargo, Kenneth K Tanabe, Donald P Lawrence, Donna S Neuberg, Keith T Flaherty, David Fisher
Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclinical models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool. <p>Experimental Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of  thousands of drug combinations in a patient-specific manner within days of biopsy...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28446294/-effect-of-hedgehog-signaling-pathway-abnormality-on-chemothe-rapeutic-resistance-of-multiple-myeloma
#17
Jia-Sheng Hu, Xiao Huang, Ying-Dan Huang, Yan-Yan Lu, Quan-Yi Lu
OBJECTIVE: To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma. METHODS: The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446279/-effect-of-stromal-cell-co-culture-on-drug-resistance-of-acute-myeloid-leukemia-cells-and-its-mechanism
#18
Han Yue, Li-Ying Liu, Xiao-Qian Wang
OBJECTIVE: To study the effect of co-culture of stromal cells and acute myeloid leukemia(AML) cells on drug resistance of AML cells and its mechanism. METHODS: Stromal cells were co-cultured with acute myeloid leukemia cell HL-60 and then were treated with DNR, HHT and Ara-C for observing the sensitivity of HL-60 cells to drugs after incubation with HS-5. At the same time, the the inhibitor LY294002 of PI3K/AKT signaling pathway was used to treat the cells, so as to explore whether the changes of HL-60 sensitivity is associated with the activation of PI3K/AKT signal pathway after co-culture of cells...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#19
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28446239/dasatinib%C3%A2-%C3%A2-gefitinib-a-non-platinum-based-combination-with-enhanced-growth-inhibitory-anti-migratory-and-anti-invasive-potency-against-human-ovarian-cancer-cells
#20
Benoît Thibault, Bertrand Jean-Claude
BACKGROUND: Ovarian cancer is the leading cause of death for gynecological cancers and the 6th cause of women cancer death in developed countries. The late stage detection, the peritoneal dissemination and the acquisition of resistance against carboplatin are the main reasons to explain this poor prognosis and strengthen the need of alternative treatments to improve the management of ovarian cancer and/or to sensitize tumors to platinum salts. Epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (Met) and cellular Src kinase (c-Src) are crucial kinases implied in ovarian tumor growth, survival, invasion and resistance to carboplatin...
April 26, 2017: Journal of Ovarian Research
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