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https://www.readbyqxmd.com/read/28938604/inflammation-and-stem-markers-association-to-pim1-pim2-kinase-induced-tumors-in-breast-and-uterus
#1
Manuel-Pedro Jiménez-García, Antonio Lucena-Cacace, María-José Robles-Frías, Irene Ferrer, Maja Narlik-Grassow, Carmen Blanco-Aparicio, Amancio Carnero
The PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938574/the-dual-pi3k-mtor-inhibitor-gsk2126458-is-effective-for-treating-solid-renal-tumours-in-tsc2-mice-through-suppression-of-cell-proliferation-and-induction-of-apoptosis
#2
Kalin Narov, Jian Yang, Paulina Samsel, Ashley Jones, Julian R Sampson, Ming Hong Shen
Tuberous sclerosis (TSC) is an inherited tumour syndrome caused by mutations in TSC1 or TSC2 that lead to aberrant activation of mTOR. Tumour responses in TSC patients to rapamycin, an allosteric inhibitor of mTOR, or its analogs are partial and reversible probably due to feedback activation of Akt. In this study, we examined the efficacy of GSK2126458, an ATP-competitive dual inhibitor of PI3K/mTOR, in comparison to rapamycin for treatment of renal tumours in genetically engineered Tsc2(+/-) mice. We found that both GSK2126458 and rapamycin caused significant reduction in number and size of solid renal tumours...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938571/preclinical-study-of-cc223-as-a-potential-anti-ovarian-cancer-agent
#3
Zhenzhen Jin, Huanfu Niu, Xuenan Wang, Lei Zhang, Qin Wang, Aijun Yang
Aberrant activation of mTOR contributes to ovarian cancer progression. CC223 is a novel and potent mTOR kinase inhibitor. The current study tested its activity against human ovarian cancer cells. We showed that CC223, at nM concentrations, inhibited survival and proliferation of established/primary human ovarian cancer cells. Further, significant apoptosis activation was observed in CC223-treated ovarian cancer cells. CC223 disrupted assembly of mTOR complex 1 (mTORC1) and mTORC2 in SKOV3 cells. Meanwhile, activation of mTORC1 and mTORC2 was almost completely blocked by CC223...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937626/aspalathin-reverts-doxorubicin-induced-cardiotoxicity-through-increased-autophagy-and-decreased-expression-of-p53-mtor-p62-signaling
#4
Rabia Johnson, Samukelisiwe Shabalala, Johan Louw, Abidemi Paul Kappo, Christo John Frederick Muller
Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937244/cardiac-at1-receptor-dependent-and-igf1-receptor-independent-signaling-is-activated-by-a-single-bout-of-resistance-exercise
#5
S Fs Melo, V G Barauna, T Fernandes, E C Carmo, C Ro Carvalho, E M Oliveira
AT1 receptor (AT1R) blockade prevents physiological cardiac hypertrophy induced by resistance training. Also, our group showed that a single bout of resistance exercise (RE) activates the AKT/mTOR which was also inhibited by AT1R blocker. Here, we investigated whether IGF1-receptor (IGF1-R) and MAPKs were also activated after a single bout of RE. Wistar rats were divided into Sedentary (SED); Sedentary treated with losartan (SED+LOS); Exercise (EX); and Exercise treated with losartan (EX+LOS). Cardiac tissue was obtained 5 and 30 minutes after 4 sets of 12 repetitions of squat exercise (80%1RM)...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936961/-effects-of-small-rna-interference-targeting-mammalian-target-of-rapamycin-on-paraquat-induced-pulmonary-fibrosis-in-rats
#6
Wenbin Yang, Xiaoqing Zhao, Ran Liang, Da Chen
OBJECTIVE: To investigate the effects of small RNA interference targeting mammalian target of rapamycin (mTOR) expression on paraquat-induced pulmonary fibrosis in rats. METHODS: Human embryonic kidney cells HEK-293 were cultured in vitro. The mTOR small interfering RNA (mTOR-siRNA) expression plasmid transfection lentivirus was constructed, and non-specific sequence plasmid with no homology to mTOR gene was set as the control. Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, paraquat model group, mTOR unrelated sequence group, and mTOR-siRNA group, with 18 rats in each group...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28936799/proteomic-features-of-colorectal-cancer-identify-tumor-subtypes-independent-of-oncogenic-mutations-and-independently-predict-relapse-free-survival
#7
Callisia N Clarke, Michael S Lee, Wei Wei, Ganiraju Manyam, Zhi-Qin Jiang, Yiling Lu, Jeffrey Morris, Bradley Broom, David Menter, Eduardo Vilar-Sanchez, Kanwal Raghav, Cathy Eng, George J Chang, Iris Simon, Rene Bernards, Michael Overman, Gordon B Mills, Dipen Maru, Scott Kopetz
BACKGROUND: The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. METHODS: We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis...
September 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28936683/trail-enhances-quinacrine-mediated-apoptosis-in-breast-cancer-cells-through-induction-of-autophagy-via-modulation-of-p21-and-dr5-interactions
#8
Sarita Das, Anmada Nayak, Sumit Siddharth, Deepika Nayak, Satya Narayan, Chanakya Nath Kundu
PURPOSE: Previously, we reported that quinacrine (QC) may cause apoptosis in breast and colon cancer cells by activating the death receptor 5 (DR5), resulting in autophagic cell death through p21 modulation. Here, we systematically evaluated the combined role of p21 and DR5 and their crosstalk in QC-mediated autophagy and apoptosis in breast cancer cells using in vitro and in vivo models. METHODS: Multiple breast cancer-derived cell lines (MCF-7, ZR-75-1, T47D, MDA-MB-231 and MCF-10A-Tr) and a mouse xenograft model were used...
September 21, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28935818/increased-mir-124-3p-in-microglial-exosomes-following-traumatic-brain-injury-inhibits-neuronal-inflammation-and-contributes-to-neurite-outgrowth-via-their-transfer-into-neurons
#9
Shan Huang, Xintong Ge, Jinwen Yu, Zhaoli Han, Zhenyu Yin, Ying Li, Fanglian Chen, Haichen Wang, Jianning Zhang, Ping Lei
Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28935770/crystal-structure-of-the-human-lysosomal-mtorc1-scaffold-complex-and-its-impact-on-signaling
#10
Mariana E G de Araujo, Andreas Naschberger, Barbara G Fürnrohr, Taras Stasyk, Theresia Dunzendorfer-Matt, Stefan Lechner, Stefan Welti, Leopold Kremser, Giridhar Shivalingaiah, Martin Offterdinger, Herbert H Lindner, Lukas A Huber, Klaus Scheffzek
LAMTOR (Late endosomal and lysosomal adaptor and mitogen activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) activator) also known as "Ragulator," controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag GTPases associated with the pentamer through their C-terminal domains, predefining the orientation for interaction with mTORC1...
September 21, 2017: Science
https://www.readbyqxmd.com/read/28935249/osteopontin-plays-a-unique-role-in-resistance-of-cd34-cd123-human-leukemia-cell-lines-kg1a-to-parthenolide
#11
Saeed Mohammadi, Mahdi Zahedpanah, Seyed Hamidollah Ghaffari, Mojgan Shaiegan, Mohsen Nikbakht, Mahin Nikugoftar
OBJECTIVES: To determine if parthenolide (PTL) is cytotoxic for leukemia-like KG1a cells and if it involves in certain molecular-mediated resistance, especially osteopontin (OPN). METHODS: PTL/daunorubicin (DNR)-treated KG1a cells were examined for viability using MTT and colony-formation assay, and stained for apoptosis using AV/PI. The gene and protein expression were evaluated by qReal-time PCR and Western blotting analysis, respectively. OPN gene was inhibited by OPN siRNA...
September 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/28935164/elevated-expression-of-neuropeptide-signaling-genes-in-the-eyestalk-ganglia-and-y-organ-of-gecarcinus-lateralis-individuals-that-are-refractory-to-molt-induction
#12
Natalie L Pitts, Hanna M Schulz, Stephanie R Oatman, Donald L Mykles
Molting is induced in decapod crustaceans via multiple leg autotomy (MLA) or eyestalk ablation (ESA). MLA removes five or more walking legs, which are regenerated and become functional appendages at ecdysis. ESA eliminates the primary source of molt-inhibiting hormone (MIH) and crustacean hyperglycemic hormone (CHH), which suppress the production of molting hormones (ecdysteroids) from the molting gland or Y-organ (YO). Both MLA and ESA are effective methods for molt induction in Gecarcinus lateralis. However, some G...
September 18, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28934384/short-syndrome-due-to-a-novel-de-novo-mutation-in-prkce-protein-kinase-c%C3%A9-impairing-torc2-dependent-akt-activation
#13
Diana Alcantara, Frances Elmslie, Martine Tetreault, Eric Bareke, Taila Hartley, Jacek Majewski, Kym Boycott, A Micheil Innes, David A Dyment, Mark O'Driscoll
SHORT syndrome is a rare, recognizable syndrome resulting from heterozygous mutations in PIK3R1 encoding a regulatory subunit of phosphoinositide-3-kinase (PI3K). The condition is characterized by short stature, intrauterine growth restriction, lipoatrophy and a facial gestalt involving a triangular face, deep set eyes, low hanging columella and small chin. PIK3R1 mutations in SHORT syndrome result in reduced signaling through the PI3K-AKT-mTOR pathway. We performed whole exome sequencing for an individual with clinical features of SHORT syndrome but negative for PIK3R1 mutation and her parents...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934193/oxidative-stress-prefrontal-cortex-hypomyelination-and-cognitive-symptoms-in-schizophrenia
#14
REVIEW
D A Maas, A Vallès, G J M Martens
Schizophrenia (SZ) is a neurodevelopmental disorder with a broad symptomatology, including cognitive symptoms that are thought to arise from the prefrontal cortex (PFC). The neurobiological aetiology of these symptoms remains elusive, yet both impaired redox control and PFC dysconnectivity have been recently implicated. PFC dysconnectivity has been linked to white matter, oligodendrocyte (OL) and myelin abnormalities in SZ patients. Myelin is produced by mature OLs, and OL precursor cells (OPCs) are exceptionally susceptible to oxidative stress...
July 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#15
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28933986/the-antiangiogenesis-effect-of-pirfenidone-in-wound-healing-in-vitro
#16
Xiao'an Liu, Yangfan Yang, Xiujuan Guo, Liling Liu, Kaili Wu, Minbin Yu
Abstracts Background: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring...
September 21, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#17
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933590/rubcn-rubicon-and-egfr-regulate-lysosomal-degradative-processes-in-the-retinal-pigment-epithelium-rpe-of-the-eye
#18
Luis Muniz-Feliciano, Teresa A Doggett, Zhenqing Zhou, Thomas A Ferguson
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933290/nutraceuticals-and-repurposed-drugs-of-phytochemical-origin-in-prevention-and-interception-of-chronic-degenerative-disease-and-cancer
#19
Adriana Albini, Barbara Bassani, Denisa Baci, Katiuscia Dallaglio, Matteo Gallazzi, Paola Corradino, Antonino Bruno, Douglas M Noonan
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932706/global-proteomics-revealed-klebsiella-pneumoniae-induced-autophagy-and-oxidative-stress-in-caenorhabditis-elegans-by-inhibiting-pi3k-akt-mtor-pathway-during-infection
#20
Arumugam Kamaladevi, Krishnaswamy Balamurugan
The enterobacterium, Klebsiella pneumoniae invades the intestinal epithelium of humans by interfering with multiple host cell response. To uncover a system-level overview of host response during infection, we analyzed the global dynamics of protein profiling in Caenorhabditis elegans using quantitative proteomics approach. Comparison of protein samples of nematodes exposed to K. pneumoniae for 12, 24, and 36 h by 2DE revealed several changes in host proteome. A total of 266 host-encoded proteins were identified by 2DE MALDI-MS/MS and LC-MS/MS and the interacting partners of the identified proteins were predicted by STRING 10...
2017: Frontiers in Cellular and Infection Microbiology
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