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https://www.readbyqxmd.com/read/28923912/exploiting-drug-addiction-mechanisms-to-select-against-mapki-resistant-melanoma
#1
Aayoung Hong, Gatien Moriceau, Lu Sun, Shirley Lomeli, Marco Piva, Robert Damoiseaux, Sheri L Holmen, Norman E Sharpless, Willy Hugo, Roger S Lo
Melanoma resistant to MAPK inhibitor(s) (MAPKi) displays loss-of-fitness upon experimental MAPKi withdrawal and, clinically, may be re-sensitized to MAPKi therapy after a drug holiday. Here, we uncovered and therapeutically exploited the mechanisms of MAPKi-addiction in MAPKi-resistant MUTBRAF or MUTNRAS melanoma. MAPKi-addiction phenotypes evident upon drug-withdrawal spanned transient cell-cycle slow-down to cell-death responses, the latter of which required a robust p-ERK rebound. Generally, drug withdrawal-induced p-ERK rebound up-regulated p38-FRA1-JUNB-CDKN1A and down-regulated proliferation, but only a robust p-ERK rebound resulted in DNA damage and parthanatos-related cell death...
September 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28879465/-nodular-lymphocyte-dominant-hodgkin-s-lymphoma-lp-cells-show-recurrent-mutations-in-dusp2-sgk1-and-junb
#2
S Hartmann
No abstract text is available yet for this article.
September 6, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28839236/association-between-genetic-polymorphisms-in-the-autophagy-related-5-gene-promoter-and-the-risk-of-sepsis
#3
Yiming Shao, Feng Chen, Yuhua Chen, Wenying Zhang, Yao Lin, Yujie Cai, Zihan Yin, Shoubao Tao, Qinghui Liao, Jianghao Zhao, Hui Mai, Yanfang He, Junbing He, Lili Cui
Previous studies demonstrated significant roles of autophagy in the pathogenesis of sepsis, but few studies focused on the effect of autophagy-related SNPs on sepsis susceptibility. In this present study, five polymorphisms of ATG5/ATG16L1 were investigated for the possible risk on sepsis in a Chinese Han population. Our results showed that ATG5 expression levels decreased with the severity of sepsis, and rs506027 T > C and rs510432 G > A were associated with sepsis progression and mortality. Moreover, the rs506027 TT and rs510432 GG carriers also exhibited increased expression levels of ATG5...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28834871/bioinformatics-analysis-of-gene-expression-profiling-for-identification-of-potential-key-genes-among-ischemic-stroke
#4
Kaihua Zhai, Xiangli Kong, Boyu Liu, Jiyu Lou
This study aimed to identify the key differentially expressed genes (DEGs) following ischemic stroke (IS).The GSE22255 microarray dataset, which contains samples from peripheral blood mononuclear cells of 20 IS patients and 20 sex- and age-matched controls, was downloaded from the Gene Expression Omnibus. After data pre-processing, DEGs were identified using the Linear Models for Microarray Data package in R. The Search Tool for the Retrieval of Interacting Genes database was used to predict the interactions among the products of DEGs, and then Cytoscape software was used to visualize the protein-protein interaction (PPI) network...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28809431/transdifferentiation-of-myoblasts-into-osteoblasts-possible-use-for-bone-therapy
#5
REVIEW
Daphne P L Lin, Revathy Carnagarin, Arun Dharmarajan, Crispin R Dass
OBJECTIVES: Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful...
August 15, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28793767/ginsenoside-20-s-rh2-induces-apoptosis-and-differentiation-of-acute-myeloid-leukemia-cells-role-of-orphan-nuclear-receptor-nur77
#6
Chengqiang Wang, Hui He, Guojun Dou, Juan Li, Xiaomei Zhang, Mingdong Jiang, Pan Li, Xiaobo Huang, Hongxi Chen, Li Li, Dajian Yang, Hongyi Qi
Ginsenoside 20(S)-Rh2 has been shown to induce apoptosis and differentiation of acute myeloid leukemia (AML) cells. However, the underlying molecular mechanisms are not fully understood. In our study, 20(S)-Rh2 induced the expression of orphan nuclear receptor Nur77 and death receptor proteins Fas, FasL, DR5, and TRAIL, as well as the cleavage of caspase 8 and caspase 3 in HL-60 cells. Importantly, shNur77 attenuated 20(S)-Rh2-induced apoptosis and Fas and DR5 expression. Meanwhile, 20(S)-Rh2 promoted Nur77 translocation from the nucleus to mitochondria and enhanced the interaction between Nur77 and Bcl-2, resulting in the exposure of the BH3 domain of Bcl-2 and activation of Bax...
September 6, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28734252/river-sequesters-atmospheric-carbon-and-limits-the-co2-degassing-in-karst-area-southwest-china
#7
Tao Zhang, Jianhong Li, Junbing Pu, Jonathan B Martin, Mitra B Khadka, Feihong Wu, Li Li, Feng Jiang, Siyu Huang, Daoxian Yuan
CO2 fluxes across water-air interfaces of river systems play important roles in regulating the regional and global carbon cycle. However, great uncertainty remains as to the contribution of these inland water bodies to the global carbon budget. Part of the uncertainty stems from limited understanding of the CO2 fluxes at diurnal and seasonal frequencies caused by aquatic metabolism. Here, we measured surface water characteristics (temperature, pH, and DO, DIC, Ca(2+) concentrations) and CO2 fluxes across the air-water interface at two transects of Guijiang River, southwest China to assess the seasonal and diurnal dynamics of fluvial carbon cycling and its potential role in regional and global carbon budgets...
December 31, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28706191/aldehyde-dehydrogenase-1-positive-nigrostriatal-dopaminergic-fibers-exhibit-distinct-projection-pattern-and-dopamine-release-dynamics-at-mouse-dorsal-striatum
#8
Carmelo Sgobio, Junbing Wu, Wang Zheng, Xi Chen, Jing Pan, Armando G Salinas, Margaret I Davis, David M Lovinger, Huaibin Cai
Aldehyde dehydrogenase 1 (ALDH1A1)-positive dopaminergic (DA) neurons at the ventral substantia nigra pars compacta (SNpc) preferentially degenerate in Parkinson's disease (PD). Their projection pattern and dopamine release properties, however, remains uncharacterized. Here we show that ALDH1A1-positive axons project predominantly to the rostral two-thirds of dorsal striatum. A portion of these axons converge on a small fraction of striosome compartments restricted to the dorsolateral striatum (DLS), where less dopamine release was measured compared to the adjacent matrix enriched with the ALDH1A1-negative axons...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687469/endoscope-assisted-neurectomy-and-inferior-alveolar-nerve-avulsion-in-treating-trigeminal-neuralgia
#9
Daiying Huang, Shuangxi Zhu, Junbing Guo, Songling Chen
OBJECTIVE: To explore endoscope-assisted surgical treatment for idiopathic trigeminal neuralgia (TN), with neurectomy and avulsion of the inferior alveolar nerve (IAN), when patients are not willing to undergo intracranial procedures. CLINICAL MATERIALS AND METHODS: Five TN patients with inferior alveolar neuralgia in the mandibular branch were admitted; endoscope-assisted inferior alveolar neurectomy and avulsion was performed for TN treatment. Clinical observation and postoperative follow-up were conducted...
September 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28659618/an-oncogenic-axis-of-stat-mediated-batf3-upregulation-causing-myc-activity-in-classical-hodgkin-lymphoma-and-anaplastic-large-cell-lymphoma
#10
A Lollies, S Hartmann, M Schneider, T Bracht, A L Weiß, J Arnolds, L Klein-Hitpass, B Sitek, M-L Hansmann, R Küppers, M A Weniger
Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30(+) lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30(+) diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein...
June 29, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28589371/activator-protein-1-ap-1-a-bridge-between-life-and-death-in-lung-epithelial-a549-cells-under-hypoxia
#11
Seema Yadav, Namita Kalra, Lilly Ganju, Mrinalini Singh
Activator protein-1 (AP-1) transcription factor plays a central role in hypoxia to modulate the expression of genes that decides the fate of the cell. The aim of the present study was to explore the role of AP-1 subunits in lung epithelial (A549) cells under hypoxia. Cell cycle studies by flow cytometry indicated that cell viability was unaffected by the initial hypoxia exposure (0.5% O2 at 37 °C) for 6 and 12 h. However, both transient cell cycle arrest and cell death was detected at 24 and 48 h. Flow cytometry and spectrofluorometry data confirmed the increase in ROS levels...
June 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28588686/effect-of-continuous-renal-replacement-therapy-on-kidney-injury-molecule-1-and-neutrophil-gelatinase-associated-lipocalin-in-patients-with-septic-acute-kidney-injury
#12
Yiming Shao, Yinqiang Fan, Yuliu Xie, Lu Yin, Yuanli Zhang, Liehua Deng, Xiaocong Sun, Xin Shao, Xinzhang Tan, Junbing He, Shiman Zhao
Kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been investigated as biomarkers for acute kidney injury (AKI). However, they are seldom investigated in patients with septic AKI treated with continuous renal replacement therapy (CRRT). The aim of the present study was to investigate the therapeutic effectiveness and possible mechanisms of CRRT in septic AKI by observing the changes in Kim-1 and NGAL levels. A group of 38 patients with septic AKI was randomly divided into the conventional drug treatment group (group A) and the CRRT group (group B)...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28586006/butein-inhibits-nf-%C3%AE%C2%BAb-ap-1-and-akt-activation-in-adult-t-cell-leukemia-lymphoma
#13
Chie Ishikawa, Masachika Senba, Naoki Mori
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) but there is no effective treatment for HTLV-1-associated diseases. Herein, we determined the effect of butein, a bioactive plant polyphenol, on cell growth, apoptosis and signaling pathways in HTLV-1-infected T-cell lines and on tumor growth in SCID mice. Treatment with butein caused a decrease in viability of HTLV-1-infected T-cell lines. T cells cultured with butein showed obvious apoptosis morphology, and cleavage of poly(ADP-ribose) polymerase with activation of caspase-3, -8 and -9...
June 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28555647/junb-is-essential-for-il-23-dependent-pathogenicity-of-th17-cells
#14
Zafrul Hasan, Shin-Ichi Koizumi, Daiki Sasaki, Hayato Yamada, Nana Arakaki, Yoshitaka Fujihara, Shiho Okitsu, Hiroki Shirahata, Hiroki Ishikawa
CD4(+) T-helper cells producing interleukin-17 (IL-17), known as T-helper 17 (TH17) cells, comprise heterogeneous subsets that exhibit distinct pathogenicity. Although pathogenic and non-pathogenic TH17 subsets share a common RORγt-dependent TH17 transcriptional programme, transcriptional regulatory mechanisms specific to each of these subsets are mostly unknown. Here we show that the AP-1 transcription factor JunB is critical for TH17 pathogenicity. JunB, which is induced by IL-6, is essential for expression of RORγt and IL-23 receptor by facilitating DNA binding of BATF at the Rorc locus in IL-23-dependent pathogenic TH17 cells, but not in TGF-β1-dependent non-pathogenic TH17 cells...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28497398/early-markers-of-myocardial-ischemia-from-the-experimental-model-to-forensic-pathology-cases-of-sudden-cardiac-death
#15
Sara Sabatasso, Milena Moretti, Patrice Mangin, Tony Fracasso
The goal of this study was to assess whether early markers of myocardial ischemia, identified in a previous experimental work, can be applied in forensic pathology cases of sudden, ischemic cardiac death. These markers include desphosphorylated connexin 43 (Cx43), JunB, TUNEL assay, myoglobin, and troponin T. Fourteen cases of sudden cardiac death with gross and/or histological signs of myocardial infarction and 14 cases of sudden cardiac death with signs of early ischemia at histology and positive immunoreactions for fibronectin and C5b-9 were investigated...
May 11, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28472164/association-study-of-mcp-1-promoter-polymorphisms-with-the-susceptibility-and-progression-of-sepsis
#16
Junbing He, Yuhua Chen, Yao Lin, Wenying Zhang, Yujie Cai, Feng Chen, Qinghui Liao, Zihan Yin, Yan Wang, Shoubao Tao, Xiaoli Lin, Pengru Huang, Lili Cui, Yiming Shao
Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) plasma concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/28458545/role-of-hedgehog-gli1-signaling-in-the-enhanced-proliferation-and-differentiation-of-mg63-cells-enabled-by-hierarchical-micro-nanotextured-topography
#17
Yao Lin, Yinghe Huang, Junbing He, Feng Chen, Yanfang He, Wenying Zhang
Hedgehog-Gli1 signaling is evolutionarily conserved and plays an essential role in osteoblast proliferation and differentiation as well as bone formation. To evaluate the role of the Hedgehog-Gli1 pathway in the response of osteoblasts to hierarchical biomaterial topographies, human MG63 osteoblasts were seeded onto smooth, microstructured, and micro-/nanotextured topography (MNT) titanium to assess osteoblast proliferation and differentiation in terms of proliferative activity, alkaline phosphatase (ALP) production, and osteogenesis-related gene expression...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28458013/aberrant-methylation-of-runx3-is-present-in-aflatoxin-b1-induced-transformation-of-the-l02r-cell-line
#18
Shan Wang, Zhini He, Daochuan Li, Bo Zhang, Miao Li, Wenxue Li, Wei Zhu, Xiumei Xing, Xiaowen Zeng, Qing Wang, Guanghui Dong, Yongmei Xiao, Wen Chen, Liping Chen
Chronic exposure to aflatoxin B1 (AFB1) is linked to the development of hepatocellular carcinoma (HCC). To identify differentially methylated genes involved in AFB1-induced cell transformation, we analyzed DNA methylation patterns in immortal human hepatocyte L02 cells expressing an oncogenic H-Ras allele (L02R cells) and AFB1-transformed L02R (L02RT-AFB1) cells by performing genome-wide methylation profiling. We treated L02R cells with 0.3μM AFB1 weekly and observed a transformed phenotype at the 17th week post-treatment...
June 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28454334/taxotere-induced-elevated-expression-of-il8-in-carcinoma-associated-fibroblasts-of-breast-invasive-ductal-cancer
#19
Yingliang Li, Guohua Rong, Hua Kang
Breast cancer is the most common malignant tumor in women worldwide, and accounts for an estimated 29% of new cases and 15% of cancer-associated mortalities each year. Invasive ductal carcinoma represents 70-80% of all breast cancer cases, which are responsible for the majority of breast cancer fatalities. Though great progress has been made in understanding the tumorigenesis and development of breast cancer, problems surrounding treatment persist. It was previously reported that carcinoma-associated fibroblasts (CAFs) may be closely associated with chemotherapy resistance...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28423685/tumor-fibroblast-interactions-stimulate-tumor-vascularization-by-enhancing-cytokine-driven-production-of-mmp9-by-tumor-cells
#20
Michelle Limoge, Alfiya Safina, Amy Beattie, Lauren Kapus, Alexander M Truskinovsky, Andrei V Bakin
Advance-stage breast carcinomas include significant amounts of fibroblasts and infiltrating immune cells which have been implicated in tumor growth, recurrence, and response to therapy. The present study investigated the contribution of fibroblasts to tumor growth using direct tumor-fibroblast co-cultures and tumor xenograft models. Our findings revealed that fibroblasts enhance breast carcinoma growth by promoting the tumor vasculature via the MMP9-dependent mechanism. In tumor-fibroblast co-cultures, fibroblasts increased expression of TGF-β, TNF, and IL-1β cytokines in tumor cells...
May 30, 2017: Oncotarget
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