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https://www.readbyqxmd.com/read/28631564/indole-3-carbinol-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-through-suppression-of-stat5-and-akt-signaling-pathways
#1
Majid Safa, Leila Jafari, Fatemeh Alikarami, Rima Manafi Shabestari, Ahmad Kazemi
Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, idenication of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627671/downregulation-of-notch1-inhibits-the-invasion-and-metastasis-of-human-gastric-cancer-cells-sgc7901-and-mkn74-in%C3%A2-vitro-through-pten-activation-and-dephosphorylation-of-akt-and-fak
#2
Xue-Song Zhang, Yan-Hua Hu, Hong-Yu Gao, Xiu-Wen Lan, Ying-Wei Xue
Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28620824/l-3-n-butylphthalide-activates-akt-mtor-signaling-inhibits-neuronal-apoptosis-and-autophagy-and-improves-cognitive-impairment-in-mice-with-repeated-cerebral-ischemia-reperfusion-injury
#3
Jing Xu, Yaping Huai, Nan Meng, Yanhong Dong, Zhijuan Liu, Qianqian Qi, Ming Hu, Mingyue Fan, Wei Jin, Peiyuan Lv
L-3-n-Butylphthalide (L-NBP) exerts neuroprotective effects in animal models of cerebral ischemia, but its potential benefits in repeated cerebral ischemia-reperfusion (RCIR) injury remain unknown. We investigated the effect of L-NBP on cognitive impairment induced by RCIR in mice. Male C57Bl/6 mice received sham surgery or bilateral common carotid artery occlusion (3 times, 20 min each) and were orally administered preoperative L-NBP (30 mg/kg/day, 7 days), postoperative L-NBP (30 or 60 mg/kg/day, 28 days) or postoperative vehicle (28 days)...
June 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28616662/perifosine-enhances-bevacizumab-induced-apoptosis-and-therapeutic-efficacy-by-targeting-pi3k-akt-pathway-in-a-glioblastoma-heterotopic-model
#4
Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Mohammad Taghi Joghataei
Bevacizumab (BVZ) as an antiangiogenesis therapy leads to a transient therapeutic efficacy in high-grade glioma. However, the proapoptotic potential of BVZ has not been well elucidated, yet. There is also a tumor resistance to BVZ that is linked to post-treatment metalloproteinases and AKT activities. Herein, the association between therapeutic efficacy and putative proapoptotic activity of low-dose BVZ either alone or in combination with a specific inhibitor of AKT called perifosine (PRF), in a glioma model was investigated...
June 14, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#5
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28562590/genetic-wiring-maps-of-single-cell-protein-states-reveal-an-off-switch-for-gpcr-signalling
#6
Markus Brockmann, Vincent A Blomen, Joppe Nieuwenhuis, Elmer Stickel, Matthijs Raaben, Onno B Bleijerveld, A F Maarten Altelaar, Lucas T Jae, Thijn R Brummelkamp
As key executers of biological functions, the activity and abundance of proteins are subjected to extensive regulation. Deciphering the genetic architecture underlying this regulation is critical for understanding cellular signalling events and responses to environmental cues. Using random mutagenesis in haploid human cells, we apply a sensitive approach to directly couple genomic mutations to protein measurements in individual cells. Here we use this to examine a suite of cellular processes, such as transcriptional induction, regulation of protein abundance and splicing, signalling cascades (mitogen-activated protein kinase (MAPK), G-protein-coupled receptor (GPCR), protein kinase B (AKT), interferon, and Wingless and Int-related protein (WNT) pathways) and epigenetic modifications (histone crotonylation and methylation)...
June 8, 2017: Nature
https://www.readbyqxmd.com/read/28551702/alpha-7-nicotinic-receptor-signaling-pathway-participates-in-the-neurogenesis-induced-by-chat-positive-neurons-in-the-subventricular-zone
#7
Jianping Wang, Zhengfang Lu, Xiaojie Fu, Di Zhang, Lie Yu, Nan Li, Yufeng Gao, Xianliang Liu, Chunmao Yin, Junji Ke, Liyuan Li, Mengmeng Zhai, Shiwen Wu, Jiahong Fan, Liang Lv, Junchao Liu, Xuemei Chen, Qingwu Yang, Jian Wang
Choline acetyltransferase-positive (ChAT(+)) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine...
May 27, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28545028/stc1-promotes-cell-apoptosis-via-nf-%C3%AE%C2%BAb-phospho-p65-ser536-in-cervical-cancer-cells
#8
Xi Pan, Binyuan Jiang, Jianhao Liu, Juan Ding, Yuehui Li, Ruili Sun, Li Peng, Changfei Qin, Shujuan Fang, Guancheng Li
Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKβ, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535302/inhibition-of-n-acetylglucosaminyltransferase-v-enhances-the-cetuximab-induced-radiosensitivity-of-nasopharyngeal-carcinoma-cells-likely-through-egfr-n-glycan-alterations
#9
Xiaomin Huang, Ting Liu, Qiongyao Wang, Weiliang Zhu, Hui Meng, Linlang Guo, Ting Wei, Jian Zhang
N-acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyses the formation of the N-linked β-1-6 branching of oligosaccharides, is related to the radiosensitivity of nasopharyngeal carcinoma (NPC). Cetuximab (C225) is an epidermal growth factor receptor (EGFR) inhibitor used as a radiosensitizer in the treatment of NPC. In this study, we used GnT-V as a molecular target to further sensitize cetuximab-treated NPC cells to radiation. The results from two NPC cell lines (CNE1 and CNE2) revealed that the silencing of GnT-V enhanced cetuximab-induced radiosensitivity by decreasing the β-1-6 branching of oligosaccharides on the EGFR...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28493079/tlr2-regulates-allergic-airway-inflammation-and-autophagy-through-pi3k-akt-signaling-pathway
#10
Xuqin Jiang, Lei Fang, Huimei Wu, Xiaodong Mei, Fang He, Peishan Ding, Rongyu Liu
Toll-like receptors (TLRs) are innate pattern recognition receptors that play a critical role in allergic inflammation, yet their contribution to autophagy in asthma remains poorly defined. Here, we investigate the role of Toll-like receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild-type (WT) and TLR2-knockout (TLR2(-/-)) C57BL/6 mice were ovalbumin-sensitized and ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell hyperplasia, and increased mucus production were observed...
May 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28483634/protein-mediated-regulation-of-the-nhe1-isoform-of-the-na-h-exchanger-in-renal-cells-a-regulatory-role-of-hsp90-and-akt-kinase
#11
Ayodeji Odunewu-Aderibigbe, Larry Fliegel
Na(+)/H(+) exchanger isoform one (NHE1) is a pH regulatory protein that is present in renal tissues and serves to remove protons from within cells and protect against intracellular acidification. NHE1 has a large 315 amino acid cytosolic regulatory domain that regulates the catalytic membrane domain. We examined protein-mediated regulation of NHE1 through the cytosolic domain. Affinity chromatography with the C-terminus of NHE1 yielded a number of NHE1 binding proteins including 14-3-3 protein, heat shock proteins (Hsp90 and Hsp70) and Na(+)/K(+) ATPase...
May 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28475617/regulation-of-the-pi3k-akt-pathway-during-decidualization-of-endometrial-stromal-cells
#12
François Fabi, Kathy Grenier, Sophie Parent, Pascal Adam, Laurence Tardif, Valérie Leblanc, Eric Asselin
Infertility is constantly increasing in Canada, where 16% of Canadian couples are experiencing difficulty conceiving. It is thought that infertility can emanate from the dysregulated communication between the embryo and the maternal endometrium. In order to allow for this window of implantation to be open at the right moment, endometrial stromal cells proliferate and differentiate by a mechanism called decidualization. Intracellular and molecular mechanisms involved in the regulation of apoptosis and cell proliferation during decidualization of the endometrium are yet to be fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28464236/neuroprotection-by-plumbagin-involves-bdnf-trkb-pi3k-akt-and-erk1-2-jnk-pathways-in-isoflurane-induced-neonatal-rats
#13
Jun-Hui Yuan, Feng Pan, Jie Chen, Cai-Er Chen, Deng-Pan Xie, Xing-Zhu Jiang, Su-Juan Guo, Jun Zhou
OBJECTIVES: This study was designed to assess the effects of plumbagin on isoflurane-induced neurotoxicity. METHODS: Neonatal Sprague Dawley rat pups were treated with plumbagin (50, 100 or 150 mg/kg body weight, orally) from postnatal day 2. The pups on postnatal day 7 were subjected to isoflurane (0.75%) exposure for 6 h. Neuronal apoptosis in the hippocampal tissues was detected by TUNEL assay and FluroJade B staining following isoflurane exposure. Protein expressions were analysed by immunoblotting...
May 2, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28463955/capilliposide-c-sensitizes-esophageal-squamous-carcinoma-cells-to-oxaliplatin-by-inducing-apoptosis-through-the-pi3k-akt-mtor-pathway
#14
Zhipeng Shen, Lixia Xu, Juan Li, Ni Zhang
BACKGROUND Although platinum-based chemotherapy is the most effective strategy for esophageal cancer, toxicity and drug resistance limit the dose administration and the application of chemotherapy. Capilliposide C (CPS-C) is isolated from the Chinese herb Lysimachia capillipes Hemsl and is approved to be effective against carcinomas. However, the activity of CPS-C against esophageal cancer remains unclear. The present study was conducted to assess the chemosensitizing effects of CPS-C for enhancing the therapeutic efficacy of oxaliplatin in esophageal squamous carcinoma cells and explore the underlying mechanism...
May 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28459364/cytotoxic-effect-of-celastrol-alone-or-in-combination-with-paclitaxel-on-anaplastic-thyroid-carcinoma-cells
#15
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-κB), and total and phospho-Akt were reduced...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28454878/salinomycin-acts-through-reducing-akt-dependent-thymidylate-synthase-expression-to-enhance-erlotinib-induced-cytotoxicity-in-human-lung-cancer-cells
#16
Chun-Liang Tung, Jyh-Cheng Chen, Chia-Hung Wu, Yi-Shuan Peng, Wen-Ching Chen, Hao-Yu Zheng, Yi-Jun Jian, Chia-Li Wei, Ya-Ting Cheng, Yun-Wei Lin
Erlotinib (Tarceva(R)) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in the treatment of human non-small cell lung cancer (NSCLC). Salinomycin, a polyether antibiotic, has been promising a novel therapeutic agent for lung cancer, and down-regulated the expression of thymidylate synthase (TS) in NSCLC cell lines. Previous study showed that against EGFR and TS was strongly synergistic cytotoxicity in NSCLC cells. In this study, we showed that erlotinib (1.25-10μM) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung squamous cell carcinoma H1703 and adenocarcinoma H1975 cells...
August 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28446154/effects-of-escitalopram-and-paroxetine-on-mtorc1-signaling-in-the-rat-hippocampus-under-chronic-restraint-stress
#17
Mi Kyoung Seo, Cheol Min Choi, Roger S McIntyre, Hye Yeon Cho, Chan Hong Lee, Rodrigo B Mansur, Yena Lee, Jae-Hon Lee, Young Hoon Kim, Sung Woo Park, Jung Goo Lee
BACKGROUND: Recent studies have suggested that the activation of mammalian target of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore, the present study evaluated whether antidepressant drugs would exert differential effects on mTOR signaling in the rat hippocampus under conditions of chronic restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for 6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg) administered after the chronic stress procedure...
April 26, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28442920/a-blockade-of-pd-l1-produced-antitumor-and-antimetastatic-effects-in-an-orthotopic-mouse-pancreatic-cancer-model-via-the-pi3k-akt-mtor-signaling-pathway
#18
Lei Zhao, Cheng Li, Fei Liu, Yonghong Zhao, Jun Liu, Ye Hua, Jinyang Liu, Jiapeng Huang, Chunlin Ge
BACKGROUND: Pancreatic cancer is one of the most aggressive and intractable malignant tumors, and most deaths from pancreatic cancer are related to metastases. It has been demonstrated in vitro that overexpression of programmed death-ligand 1 (PD-L1) correlates with a lack of phosphatase and tensin homologue (PTEN) expression in pancreatic cancer tissue. This loss of PTEN expression may aberrantly activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, and thereby promote tumor cell survival, proliferation, and disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28423625/inhibition-activity-of-a-disulfide-stabilized-diabody-against-basic-fibroblast-growth-factor-in-lung-cancer
#19
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
#20
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 TNBC 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
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