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https://www.readbyqxmd.com/read/28423625/inhibition-activity-of-a-disulfide-stabilized-diabody-against-basic-fibroblast-growth-factor-in-lung-cancer
#1
Yaxiong Cai, Shuange Yao, Jiangchuan Zhong, Jinxia Zhang, Haowu Jiang, Yanrui Deng, Ning Deng
The over-expression of basic fibroblast growth factor (bFGF) plays a crucial role in the development, invasion and metastasis of lung cancer. Therefore, neutralizing antibodies against bFGF may inhibit the growth of lung cancer. In this study, a Disulfide-stabilized diabody (ds-Diabody) against bFGF was constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the position of VH44 and VL100 in the scFv. The ds-Diabody was constructed and expressed in Pichia pastoris. We found that the ds-Diabody against bFGF could efficiently suppress the proliferation, migration and invasion of human lung cancer A549 cells in vitro...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418078/induction-of-mitochondrial-apoptotic-pathway-in-triple-negative-breast-carcinoma-cells-by-methylglyoxal-via-generation-of-reactive-oxygen-species
#2
Anirban Roy, Manisha Ahir, Saurav Bhattacharya, Pravat Kumar Parida, Arghya Adhikary, Kuladip Jana, Manju Ray
Triple negative breast cancer (TNBC) tends to form aggressive tumors associated with high mortality and morbidity which urge the need for development of new therapeutic strategies. Recently the normal metabolite Methylglyoxal (MG) has been documented for its anti-proliferative activity against human breast cancer. However, the mode of action of MG against triple negative breast cancer remains open to question. In our study, we investigated the anticancer activity of MG in MDA MB 231 and 4T1 TNBC cell lines and elucidated the underlying mechanisms...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28412732/small-molecule-inhibitor-screening-identifified-hsp90-inhibitor-17-aag-as-potential-therapeutic-agent-for-gallbladder-cancer
#3
Helga Weber, José R Valbuena, Mustafa A Barbhuiya, Stefan Stein, Hana Kunkel, Patricia García, Carolina Bizama, Ismael Riquelme, Jaime A Espinoza, Stephen E Kurtz, Jeffrey W Tyner, Juan Francisco Calderon, Alejandro H Corvalán, Manuel Grez, Akhilesh Pandey, Pamela Leal-Rojas, Juan C Roa
Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411582/dexmedetomidine-attenuates-propofol-induce-neuroapoptosis-partly-via-the-activation-of-the-pi3k-akt-gsk3%C3%AE-pathway-in-the-hippocampus-of-neonatal-rats
#4
Jing Lv, Yi Wei, Yanhua Chen, Xu Zhang, Zheng Gong, Yage Jiang, Qin Gong, Lifang Zhou, Hao Wang, Yubo Xie
Recent studies have demonstrated that propofol causes neurodegeneration in developing brains. Evidence has shown that dexmedetomidine has neuroprotective effects. However, whether dexmedetomidine can reduce propofol-induced neuroapoptosis and by what mechanisms it acts remain unclear. We investigated whether dexmedetomidine can attenuate propofol-induced neuroapoptosis by disturbing the PI3K/Akt/GSK3β pathway during brain development. Seven-day-old rats were randomly exposed to 100mg/kg propofol and 100mg/kg propofol plus different doses of dexmedetomidine or 100mg/kg propofol and 75μg/kg dexmedetomidine plus PI3K inhibitor LY294002 or GSK3β inhibitor TDZD-8...
March 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28406693/polychlorinated-biphenyl-153-in-lipid-medium-modulates-differentiation-of-human-adipocytes
#5
D Mullerova, M Pesta, J Dvorakova, M Cedikova, V Kulda, P Dvorak, V Bouchalová, M Kralickova, V Babuska, J Kuncova, J Langmajerova, L Muller
Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2´,4,4´,5,5´-hexachlorobiphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modelling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28390265/acute-exposure-of-primary-rat-soleus-muscle-to-zilpaterol-hcl-%C3%AE-2-adrenergic-agonist-tnf%C3%AE-or-il-6-in-culture-increases-glucose-oxidation-rates-independent-of-the-impact-on-insulin-signaling-or-glucose-uptake
#6
Caitlin N Cadaret, Kristin A Beede, Hannah E Riley, Dustin T Yates
Recent studies show that adrenergic agonists and inflammatory cytokines can stimulate skeletal muscle glucose uptake, but it is unclear if glucose oxidation is similarly increased. Thus, the objective of this study was to determine the effects of ractopamine HCl (β1 agonist), zilpaterol HCl (β2 agonist), TNFα, and IL-6 on glucose uptake and oxidation rates in unstimulated and insulin-stimulated soleus muscle strips from adult Sprague-Dawley rats. Effects on phosphorylation of Akt (phospho-Akt), p38 MAPK (phospho-p38), and p44/42 MAPK (phospho-p44/42) was also determined...
April 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28388784/beta-ecdysone-protects-mouse-osteoblasts-from-glucocorticoid-induced-apoptosis-in-vitro
#7
Wei-Wei Dai, Li-Bo Wang, Guo-Qin Jin, Hong-Jin Wu, Jie Zhang, Cheng-Long Wang, Yuan-Ji Wei, Joon-Ho Lee, Yu-An Evan Lay, Wei Yao
Glucocorticoid-induced osteoporosis is a common form of secondary osteoporosis. Glucocorticoids affect both bone formation and resorption, and prolonged glucocorticoid exposure can suppress osteoblast activities. beta-Ecdysone, found in many plants, is involved in protein synthesis, carbohydrate and lipid metabolism, and immunologic modulation. Here, we evaluated the effects of beta-ecdysone on osteoblast viability by assessing apoptosis following treatment with excess glucocorticoids. Mouse bone marrow stromal cells were induced to differentiate and grow into osteoblasts, and then treated with 10 µM glucocorticoid and 10, 1, or 0...
April 7, 2017: Planta Medica
https://www.readbyqxmd.com/read/28386365/calpain-1-regulates-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-human-lung-epithelial-cells-via-pi3k-akt-signaling-pathway
#8
Wei-Jun Tan, Qiu-Yue Tan, Ting Wang, Min Lian, Li Zhang, Zhen-Shun Cheng
Cell proliferation, transformation, and epithelial-mesenchymal transition (EMT) are key processes involved in the development of idiopathic pulmonary fibrosis (IPF). This study investigated the regulatory factors and signaling pathways that mediate EMT in the human type II alveolar epithelial A549 cell line. A549 cells were cultured in RPMI-1640 medium and allocated to the following four groups: blank control group or treated with transforming growth factor-β1 (TGF-β1), TGF-β1 + PD 150606 (a calpain 1 inhibitor), or PD 150606...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28374891/short-term-hypoxia-reverses-ox-ldl-induced-cd36-and-glut4-switching-metabolic-pathways-in-h9c2-cardiomyoblast-cells
#9
Yeh-Peng Chen, Hsi-Hsien Hsu, Rathinasamy Baskaran, Su-Ying Wen, Chia-Yao Shen, Cecilia-Hsuan Day, Tsung-Jung Ho, Viswanadha Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
High levels of circulating low-density lipoproteins (LDL, plasma proteins that carry cholesterol and triglycerides) are associated with type 2 diabetes, arteriosclerosis, obesity and hyperlipidemia. In the heart, the accumulation of oxidized low-density lipoprotein (Ox-LDL) has been proposed to play a role in the development of cardiovascular disease. We obtain cholesterol from animals and animal-derived foods such as milk, eggs and cheese. In previous studies, the ratio of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was shown to be important for our health...
April 4, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28365943/papaverine-selectively-inhibits-human-prostate-cancer-cell-pc-3-growth-by-inducing-mitochondrial-mediated-apoptosis-cell-cycle-arrest-and-downregulation-of-nf-%C3%AE%C2%BAb-pi3k-akt-signalling-pathway
#10
Hang Huang, Lin-Jin Li, Hai-Bo Zhang, An-Yang Wei
PURPOSE: The main objective of the current research work was to investigate the antitumor effects of papaverine in PC-3 human prostate cancer cells along with testing its toxicity in the normal human fibroblast (NHF) cells. METHODS: The cytotoxic effects of papaverine were examined by the MTT cell viability assay. Flow cytometry using annexin V-FITC/PI was used to study the effects on apoptosis, including its quantification. Effects on cell cycle progression were analyzed by flow cytometry while as effects on apoptosis-related proteins, NF-kB and PI3K/Akt pathways were estimated by Western blot assay...
January 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28345550/recombinant-human-erythropoietin-augments-neovascularization-responses-in-a-neonatal-rat-model-of-premature-brain-damage-by-phosphatidylinositol-3-kinase-akt-pathway
#11
Da-Fan Yu, Li-Hua Zhu, Li Jiang
BACKGROUND: Recombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. METHODS: Postnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#12
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28338494/combined-knockdown-of-d-dopachrome-tautomerase-and-migration-inhibitory-factor-inhibits-the-proliferation-migration-and-invasion-in-human-cervical-cancer
#13
Qingying Wang, Yingze Wei, Jiawen Zhang
OBJECTIVE: D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far. METHODS: D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo...
March 23, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28335495/brain-derived-neurotrophic-factor-loaded-ps80-pbca-nanocarrier-for-in-vitro-neural-differentiation-of-mouse-induced-pluripotent-stem-cells
#14
Chiu-Yen Chung, Martin Hsiu-Chu Lin, I-Neng Lee, Tsong-Hai Lee, Ming-Hsueh Lee, Jen-Tsung Yang
Brain derived neurotrophic factor (BDNF) can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC) was constructed to deliver plasmid DNAs (pDNAs) containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF). The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs) to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting...
March 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28300578/cellular-interactions-of-the-phosphorylated-form-of-akt-in-prostate-cancer
#15
Kai H Hammerich, Anna Frolov, Rile Li, Michael Ittmann, Gustavo E Ayala
Phospho-Akt (P-Akt1) promotes proliferation and increased survival in vitro and plays an important role in prostate cancer (PCa) progression as well as the prediction of the probability of recurrence. In this study, the goal was to demonstrate the involvement and impact of P-Akt1 on cellular interactions, biomechanisms and pathways in PCa. Tissue microarrays from 640 PCa patients were immunostained with various antibodies. Ki67 was used to measure proliferation index and Tunnel for apoptotic index. Increased expression of P-Akt1 was associated with an increased proliferation, but inversely correlated with apoptotic index...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28289208/specific-deletion-of-lkb1-stk11-in-the-m%C3%A3-llerian-duct-mesenchyme-drives-hyperplasia-of-the-periurethral-stroma-and-tumorigenesis-in-male-mice
#16
Jitu W George, Amanda L Patterson, Pradeep S Tanwar, André Kajdacsy-Balla, Gail S Prins, Jose M Teixeira
Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11(CKO) mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288548/upregulated-glutathione-transferase-omega-1-correlates-with-progression-of-urinary-bladder-carcinoma
#17
Tatjana Djukic, Tatjana Simic, Marija Pljesa-Ercegovac, Marija Matic, Sonja Suvakov, Vesna Coric, Dejan Dragicevic, Ana Savic-Radojevic
OBJECTIVES: Newly discovered glutathione transferase omega 1 (GSTO1-1) plays an important role in the glutathionylation cycle, a significant mechanism of protein function regulation. GSTO1-1 expression pattern has not been studied in transitional cell carcinoma (TCC), as yet. METHODS: A total of 56 TCC tumor and corresponding non-tumor specimens were investigated. Glutathione content and thioltransferase activity were measured spectrophotometrically. Protein-glutathione mixed disulfides were measured fluorimetrically...
March 13, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28285180/noninvasive-bioluminescence-imaging-of-akt-kinase-activity-in-subcutaneous-and-orthotopic-nsclc-xenografts-correlation-of-akt-activity-with-tumor-growth-kinetics
#18
Karina Suchowski, Thomas Pöschinger, Alnawaz Rehemtulla, Michael Stürzl, Werner Scheuer
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non-small cell lung cancer cell line, engineered to express BAR, enabled the evaluation of compounds targeting the EGFR/PI3K/AKT pathway in vitro as well as in mouse models. We found that erlotinib treatment of resistant A549 subcutaneous and orthotopic xenografts resulted in significant AKT inhibition as determined by an 8- to 13-fold (P < ...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28281841/lncrna-nonratt021972-sirna-normalized-the-dysfunction-of-hepatic-glucokinase-through-akt-signaling-in-t2dm-rats
#19
Miaomiao Song, Lifang Zou, Lichao Peng, Shuangmei Liu, Bing Wu, Zhihua Yi, Yun Gao, Chunping Zhang, Hong Xu, Yurong Xu, Mengxia Tang, Shouyu Wang, Yun Xue, Tianyu Jia, Shanhong Zhao, Shangdong Liang, Guilin Li
Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3β. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases. AIMS: This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats...
March 10, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28281555/nf-%C3%AE%C2%BAb-p50-activation-associated-with-immune-dysregulation-confers-poorer-survival-for-diffuse-large-b-cell-lymphoma-patients-with-wild-type-p53
#20
Qingqing Cai, Meifeng Tu, Zijun Y Xu-Monette, Ruifang Sun, Ganiraju C Manyam, Xiaolu Xu, Alexander Tzankov, Eric D Hsi, Michael B Møller, L Jeffrey Medeiros, Chi Young Ok, Ken H Young
Dysregulated NF-κB signaling is critical for lymphomagenesis, however, the expression and clinical relevance of NF-κB subunit p50 in diffuse large B-cell lymphoma have not been evaluated. In this study, we analyzed the prognostic significance and gene expression signatures of p50 nuclear expression as a surrogate for p50 activation in 465 patients with de novo diffuse large B-cell lymphoma. We found that p50(+) nuclear expression, observed in 34.6% of diffuse large B-cell lymphoma, predominantly composed of activated B-cell-like subtype, was an independent adverse prognostic factor in patients with activated B-cell-like diffuse large B-cell lymphoma...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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