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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/28232663/camp-signaling-increases-histone-deacetylase-8-expression-via-the-epac2-rap1a-akt-pathway-in-h1299-lung-cancer-cells
#1
Ji-Yeon Park, Yong-Sung Juhnn
This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression...
February 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28232662/resveratrol-suppresses-breast-cancer-cell-invasion-by-inactivating-a-rhoa-yap-signaling-axis
#2
Yu Na Kim, So Ra Choe, Kyung Hwa Cho, Do Yeun Cho, Jaeku Kang, Chang Gyo Park, Hoi Young Lee
Hippo/YAP signaling is implicated in tumorigenesis and progression of various cancers. By inhibiting a plethora signaling cascades, resveratrol has strong anti-tumorigenic and anti-metastatic activity. In the present study, we demonstrate that resveratrol decreases the expression of YAP target genes. In addition, our data showed that resveratrol attenuates breast cancer cell invasion through the activation of Lats1 and consequent inactivation of YAP. Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation...
February 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28209986/nf-%C3%AE%C2%BAb-signaling-regulates-cell-autonomous-regulation-of-cxcl10-in-breast-cancer-4t1-cells
#3
Won Jong Jin, Bongjun Kim, Darong Kim, Hea-Young Park Choo, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells...
February 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28209985/ig-like-domain-6-of-vcam-1-is-a-potential-therapeutic-target-in-tnf%C3%AE-induced-angiogenesis
#4
Taek-Keun Kim, Chang Sik Park, Hee-Jun Na, Kangseung Lee, Aerin Yoon, Junho Chung, Sukmook Lee
Tumor necrosis factor alpha (TNFα)-induced angiogenesis plays important roles in the progression of various diseases, including cancer, wet age-related macular degeneration, and rheumatoid arthritis. However, the relevance and role of vascular cell adhesion molecule-1 (VCAM-1) in angiogenesis have not yet been clearly elucidated. In this study, VCAM-1 knockdown shows VCAM-1 involvement in TNFα-induced angiogenesis. Through competitive blocking experiments with VCAM-1 Ig-like domain 6 (VCAM-1-D6) protein, we identified VCAM-1-D6 as a key domain regulating TNFα-induced vascular tube formation...
February 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28186086/hoxc10-suppresses-browning-of-white-adipose-tissues
#5
Yvonne Ng, Shi-Xiong Tan, Sook Yoong Chia, Hwee Yim Angeline Tan, Sin Yee Gun, Lei Sun, Wanjin Hong, Weiping Han
Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes...
February 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28186085/hepatitis-b-virus-x-protein-mediated-non-coding-rna-aberrations-in-the-development-of-human-hepatocellular-carcinoma
#6
REVIEW
Bei Zhang, Siqi Han, Bing Feng, Xiaoyuan Chu, Longbang Chen, Rui Wang
Hepatitis B virus (HBV) has an important role in the development of human hepatocellular carcinoma (HCC). Accumulated evidence has shown that HBV-encoded X protein (HBx) can induce both genetic alterations in tumor suppressor genes and oncogenes, as well as epigenetic aberrations in HCC pathogens. Non-coding RNAs (ncRNAs) mainly include microRNAs and long non-coding RNAs (lncRNAs). Although ncRNAs cannot code proteins, growing evidence has shown that they have various important biological functions in cell proliferation, cell cycle control, anti-apoptosis, epithelial-mesenchymal transition, tumor invasion and metastasis...
February 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28154372/therapeutic-effect-of-the-immunomodulatory-drug-lenalidomide-but-not-pomalidomide-in-experimental-models-of-rheumatoid-arthritis-and-inflammatory-bowel-disease
#7
Belen Lopez-Millan, Rafael Diaz de la Guardia, Heleia Roca-Ho, Carmen M García-Herrero, Jessie R Lavoie, Michael Rosu-Myles, Elena Gonzalez-Rey, Francisco O'Valle, Gabriel Criado, Mario Delgado, Pablo Menendez
Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis...
February 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28154371/oxidative-stress-and-calcium-dysregulation-by-palmitate-in-type-2-diabetes
#8
REVIEW
Luong Dai Ly, Shanhua Xu, Seong-Kyung Choi, Chae-Myeong Ha, Themis Thoudam, Seung-Kuy Cha, Andreas Wiederkehr, Claes B Wollheim, In-Kyu Lee, Kyu-Sang Park
Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca(2+) homeostasis...
February 3, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28127050/hmscs-suppress-neutrophil-dominant-airway-inflammation-in-a-murine-model-of-asthma
#9
Gyong Hwa Hong, Hyouk-Soo Kwon, Kyoung Young Lee, Eun Hee Ha, Keun-Ai Moon, Seong Who Kim, Wonil Oh, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho
Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation...
January 27, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28127049/hhip-regulates-tumor-stroma-mediated-upregulation-of-tumor-angiogenesis
#10
Vijayendra Agrawal, Dong Young Kim, Young-Guen Kwon
Tumor growth is governed by the coordinated action of various types of cells that are present in the tumor environment. Fibroblasts, which constitute a major fraction of the stroma, participate actively in various signaling events and regulate tumor development and metastasis. The Hedgehog (Hh) pathway plays an important role in promoting tumor malignancy via fibroblasts; however, the role of hedgehog interacting protein (hhip; inhibitor of Hh pathway) in tumor growth is poorly understood. Here we implanted B16F10 tumors in hhip+/- mice to study the tumor growth characteristics and the vascular phenotype...
January 27, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104914/docosahexaenoic-acid-mediated-protein-aggregates-may-reduce-proteasome-activity-and-delay-myotube-degradation-during-muscle-atrophy-in-vitro
#11
Seung Kyun Shin, Ji Hyeon Kim, Jung Hoon Lee, Young Hoon Son, Min Wook Lee, Hak Joong Kim, Sue Ah Noh, Kwang Pyo Kim, In-Gyu Kim, Min Jae Lee
Proteasomes are the primary degradation machinery for oxidatively damaged proteins that compose a class of misfolded protein substrates. Cellular levels of reactive oxygen species increase with age and this cellular propensity is particularly harmful when combined with the age-associated development of various human disorders including cancer, neurodegenerative disease and muscle atrophy. Proteasome activity is reportedly downregulated in these disease conditions. Herein, we report that docosahexaenoic acid (DHA), a major dietary omega-3 polyunsaturated fatty acid, mediates intermolecular protein cross-linkages through oxidation, and the resulting protein aggregates potently reduce proteasomal activity both in vitro and in cultured cells...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104913/exosome-derived-micrornas-in-cancer-metabolism-possible-implications-in-cancer-diagnostics-and-therapy
#12
REVIEW
Marco Tomasetti, Wan Lee, Lory Santarelli, Jiri Neuzil
Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104912/paclitaxel-resistant-cancer-cell-derived-secretomes-elicit-abcb1-associated-docetaxel-cross-resistance-and-escape-from-apoptosis-through-foxo3a-driven-glycolytic-regulation
#13
Mark Borris D Aldonza, Ji-Young Hong, Sang Kook Lee
Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082743/adipose-stem-cell-derived-nanovesicles-inhibit-emphysema-primarily-via-an-fgf2-dependent-pathway
#14
You-Sun Kim, Ji-Young Kim, RyeonJin Cho, Dong-Myung Shin, Sei Won Lee, Yeon-Mok Oh
Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100 nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082742/gene-metabolite-network-analysis-in-different-nonalcoholic-fatty-liver-disease-phenotypes
#15
Xiao-Lin Liu, Ya-Nan Ming, Jing-Yi Zhang, Xiao-Yu Chen, Min-De Zeng, Yi-Min Mao
We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082741/bioinformatic-identification-of-prognostic-signature-defined-by-copy-number-alteration-and-expression-of-ccne1-in-non-muscle-invasive-bladder-cancer
#16
Bic-Na Song, Seon-Kyu Kim, In-Sun Chu
Non-muscle invasive bladder cancer (NMIBC) patients frequently fail to respond to treatment and experience disease progression because of their clinical and biological diversity. In this study, we identify a prognostic molecular signature for predicting the heterogeneity of NMIBC by using an integrative analysis of copy number and gene expression data. We analyzed the copy number and gene expression profiles of 404 patients with bladder cancer obtained from The Cancer Genome Atlas (TCGA) consortium. Of the 14 molecules with significant copy number alterations that were previously reported, 13 were significantly correlated with copy number and expression changes...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28082740/epigenetic-regulation-and-chromatin-remodeling-in-learning-and-memory
#17
REVIEW
Somi Kim, Bong-Kiun Kaang
Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications...
January 13, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27980343/il-17a-exacerbates-diabetic-retinopathy-by-impairing-m%C3%A3-ller-cell-function-via-act1-signaling
#18
Ao-Wang Qiu, Zheng Bian, Ping-An Mao, Qing-Huai Liu
Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27980342/evaluation-of-a-tyrosine-kinase-peptide-microarray-for-tyrosine-kinase-inhibitor-therapy-selection-in-cancer
#19
Mariette Labots, Kristy J Gotink, Henk Dekker, Kaamar Azijli, Johannes C van der Mijn, Charlotte M Huijts, Sander R Piersma, Connie R Jiménez, Henk M W Verheul
Personalized cancer medicine aims to accurately predict the response of individual patients to targeted therapies, including tyrosine kinase inhibitors (TKIs). Clinical implementation of this concept requires a robust selection tool. Here, using both cancer cell lines and tumor tissue from patients, we evaluated a high-throughput tyrosine kinase peptide substrate array to determine its readiness as a selection tool for TKI therapy. We found linearly increasing phosphorylation signal intensities of peptides representing kinase activity along the kinetic curve of the assay with 7...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27932791/migration-and-invasion-of-drug-resistant-lung-adenocarcinoma-cells-are-dependent-on-mitochondrial-activity
#20
Ji Hoon Jeon, Dong Keon Kim, Youngmi Shin, Hee Yeon Kim, Bomin Song, Eun Young Lee, Jong Kwang Kim, Hye Jin You, Heesun Cheong, Dong Hoon Shin, Seong-Tae Kim, Jae-Ho Cheong, Soo Youl Kim, Hyonchol Jang
A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated...
December 9, 2016: Experimental & Molecular Medicine
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