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https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#1
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28794516/experimental-arthritis-puma-reduces-inflammation-in-arthritic-joints
#2
Dario Ummarino
No abstract text is available yet for this article.
August 10, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28783428/apex-predators-rockshelters-and-zoonoses-in-the-patagonian-holocene
#3
Martin Fugassa, Romina Petrigh
Carnivorous mammals are a trophic guild with an important role in the dissemination of parasite infective stages (larvae, eggs, cysts, and oocysts). In the present study, new samples of coprolites attributed to carnivorous mammals, obtained from two archaeological caves, were analyzed for the presence of parasites, with the aim to increase the knowledge about parasites in rockshelters that could have spread to humans and other mammals. To this purpose, fragments of 3 coprolites from Cerro Casa de Piedra, cave 5 (CCP5) and cave 7 (CCP7) were examined...
August 7, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28783173/synergistic-activity-and-heterogeneous-acquired-resistance-of-combined-mdm2-and-mek-inhibition-in-kras-mutant-cancers
#4
A N Hata, S Rowley, H L Archibald, M Gomez-Caraballo, F M Siddiqui, F Ji, J Jung, M Light, J S Lee, L Debussche, S Sidhu, R I Sadreyev, J Watters, J A Engelman
There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers (NSCLC) and colorectal carcinomas that harbor wild-type TP53. The combination of pimasertib (MEK inhibitor) and SAR405838 (MDM2 inhibitor) was synergistic and induced the expression of PUMA and BIM, led to apoptosis and growth inhibition in vitro, and tumor regression in vivo...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28757384/znf509s1-downregulates-puma-by-inhibiting-p53k382-acetylation-and-p53-dna-binding
#5
Bu-Nam Jeon, Jae-Hyeon Yoon, Dohyun Han, Min-Kyeong Kim, Youngsoo Kim, Seo-Hyun Choi, Jiyang Song, Kyung-Sup Kim, Kunhong Kim, Man-Wook Hur
Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28750090/target-specificity-in-vivo-pharmacokinetics-and-efficacy-of-the-putative-stat3-inhibitor-ly5-in-osteosarcoma-ewing-s-sarcoma-and-rhabdomyosarcoma
#6
Peter Y Yu, Heather L Gardner, Ryan Roberts, Hakan Cam, Seethalakshmi Hariharan, Ling Ren, Amy K LeBlanc, Hui Xiao, Jiayuh Lin, Denis C Guttridge, Xiaokui Mo, Chad E Bennett, Christopher C Coss, Yonghua Ling, Mitch A Phelps, Peter Houghton, Cheryl A London
BACKGROUND: STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. METHODS AND FINDINGS: An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization...
2017: PloS One
https://www.readbyqxmd.com/read/28749292/molecular-detection-of-infectious-pathogens-of-the-upper-respiratory-tract-in-captive-nondomestic-felids
#7
Valéria M Lara, Julia C Benassi, Shayne P Bisetto, Trícia M de Oliveira, Helena L Ferreira, João P Araújo Júnior, Adriano B Carregaro
Upper respiratory tract disease is a complex infectious disease process with multiple pathogens involved. Identification of infectious agents in wild animals is of great importance for wildlife conservation. The aim of this study was to evaluate the molecular detection of feline herpesvirus type 1, feline calicivirus (FCV), Bordetella bronchiseptica , Chlamydophila felis , and Mycoplasma felis using ocular and nasal swabs in three species of captive nondomestic felids. Mycoplasma felis was detected in two ocular samples of Puma concolor and in one nasal sample of one Panthera onca ...
June 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28747638/puma-gene-delivery-to-synoviocytes-reduces-inflammation-and-degeneration-of-arthritic-joints
#8
Saw-See Hong, Hubert Marotte, Guillaume Courbon, Gary S Firestein, Pierre Boulanger, Pierre Miossec
In rheumatoid arthritis (RA), the proliferation of fibroblast-like synoviocytes (FLS) is the cause of chronic inflammation in joints and of joint damage. Delivery of the pro-apoptotic gene PUMA to FLS via human adenovirus type 5 (HAdV5) vectors has been tested as a therapeutic approach, but efficiency is hampered by low transduction, as FLS do not express HAdV5 receptors on the cell surface. Here we show that efficient transduction of PUMA in FLS can be achieved by conjugating HAdV5 to a baculovirus, which binds to the cell surface via the envelope glycoprotein Gp64...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28737911/platform-for-unified-molecular-analysis-puma
#9
Mariana González-Medina, José L Medina-Franco
We introduce a free platform for chemoinformatic-based diversity analysis and visualization of chemical space of user supplied data sets. Platform for Unified Molecular Analysis (PUMA) integrates metrics used to characterize compound databases including visualization of chemical space, scaffold content, and analysis of chemical diversity. The user's input is a file with SMILES, database names, and compound IDs. PUMA computes molecular properties of pharmaceutical relevance, Murcko scaffolds, and diversity analysis...
August 8, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28730463/exploring-new-alleles-for-frost-tolerance-in-winter-rye
#10
Wiltrud Erath, Eva Bauer, D Brian Fowler, Andres Gordillo, Viktor Korzun, Mira Ponomareva, Malthe Schmidt, Brigitta Schmiedchen, Peer Wilde, Chris-Carolin Schön
Rye genetic resources provide a valuable source of new alleles for the improvement of frost tolerance in rye breeding programs. Frost tolerance is a must-have trait for winter cereal production in northern and continental cropping areas. Genetic resources should harbor promising alleles for the improvement of frost tolerance of winter rye elite lines. For frost tolerance breeding, the identification of quantitative trait loci (QTL) and the choice of optimum genome-based selection methods are essential. We identified genomic regions involved in frost tolerance of winter rye by QTL mapping in a biparental population derived from a highly frost tolerant selection from the Canadian cultivar Puma and the European elite line Lo157...
July 20, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28725954/proteasome-stress-triggers-death-of-sh-sy5y-and-t98g-cells-via-different-cellular-mechanisms
#11
Ivana Pilchova, Katarina Klacanova, Katarina Dibdiakova, Simona Saksonova, Andrea Stefanikova, Eva Vidomanova, Lucia Lichardusova, Jozef Hatok, Peter Racay
Overload or dysfunction of ubiquitin-proteasome system (UPS) is implicated in mechanisms of neurodegeneration associated with neurodegenerative diseases, e.g. Parkinson and Alzheimer disease, and ischemia-reperfusion injury. The aim of this study was to investigate the possible association between viability of neuroblastoma SH-SY5Y and glioblastoma T98G cells treated with bortezomib, inhibitor of 26S proteasome, and accumulation of ubiquitin-conjugated proteins with respect to direct cytotoxicity of aggregates of ubiquitin-conjugated proteins...
July 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28724666/braf-inhibitors-amplify-the-pro-apoptotic-activity-of-mek-inhibitors-by-inducing-er-stress-in-nras-mutant-melanoma
#12
Heike Niessner, Tobias Sinnberg, Corinna Kosnopfel, Keiran S M Smalley, Daniela Beck, Christian Praetorius, Marion Mai, Stefan Beissert, Dagmar Kulms, Martin Schaller, Claus Garbe, Keith T Flaherty, Dana Westphal, Ines Wanke, Friedegund Meier
<p>NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its pro-apoptotic activity in BRAF-mutant melanoma...
July 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28715817/amp010014a09-in-sus-scrofa-encodes-an-analog-of-g-protein-coupled-receptor-109a-which-mediates-the-anti-inflammatory-effects-of-beta-hydroxybutyric-acid
#13
Guangxin Chen, Shoupeng Fu, Wenqian Feng, Bingxu Huang, Shiyao Xu, Wei Wang, Juxiong Liu
BACKGROUND: Hydroxy-carboxylic acid receptor 2 (HCA2, also called GPR109A) belongs to the G protein-coupled receptor (GPCR) family and is found in humans, rats, mice, hamsters and guinea pigs, but there are almost no reports of this protein in other species. In this investigation, we speculated that AMP010014A09 (AMP+) is a homologue of GPR109A in swine. METHODS: To test this hypothesis, the following experiments were designed: monocytes isolated from the peripheral blood of swine were treated with LPS after pretreating with or without β-hydroxybutyric acid (BHBA), and the levels of pro-inflammatory cytokines and inflammatory proteins were assessed...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28714963/fhit-loss-confers-cisplatin-resistance-in-lung-cancer-via-the-akt-nf-%C3%AE%C2%BAb-slug-mediated-puma-reduction
#14
D-W Wu, M-C Lee, N-Y Hsu, T-C Wu, J-Y Wu, Y-C Wang, Y-W Cheng, C-Y Chen, H Lee
This corrects the article DOI: 10.1038/onc.2014.184.
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28713983/malformin%C3%A2-a1-treatment-alters-invasive-and-oncogenic-phenotypes-of-human-colorectal-cancer-cells-through-stimulation-of-the-p38-signaling-pathway
#15
Sun-Young Park, Hyung-Hoon Oh, Young-Lan Park, Hyung-Min Yu, Dae-Seong Myung, Sung-Bum Cho, Wan-Sik Lee, Daeho Park, Young-Eun Joo
Malformin A1 (MA1), a cyclic pentapeptide isolated from Aspergillus niger, has been found to possess a range of bioactive properties including antibacterial activity. However, it is unclear whether MA1 exerts an anticancer effect or not. In this study, we conducted in vitro experiments to investigate its anticancer properties in human colorectal cancer cells. The effect of MA1 on human colorectal cancer cells, SW480 and DKO1, was examined by the WST-1 cell viability assay, inverted microscopy, 5-bromo-2-deoxyuridine (BrdU) incorporation, flow cytometry, DNA fragmentation, wound healing, Transwell assays, and western blotting...
July 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28710020/nrf2-deficiency-exacerbates-ochratoxin-a-induced-toxicity-in-vitro-and-in-vivo
#16
Agnieszka Loboda, Anna Stachurska, Mateusz Sobczak, Paulina Podkalicka, Olga Mucha, Alicja Jozkowicz, Jozef Dulak
Several mechanisms are postulated to be responsible for nephrotoxic and nephrocarcinogenic activities of mycotoxin and food contaminant, ochratoxin A (OTA). Although Nrf2 transcription factor was suggested to be involved in OTA-mediated renal injury, comprehensive study evaluating the effect of OTA toxicity in Nrf2 knock-out mice with special regard to sex-dependency has not been performed yet. Our results clearly show exacerbated OTA toxicity in porcine tubular epithelial cells after shRNA-mediated Nrf2 inhibition as well as in proximal tubular cells isolated from Nrf2(-/-) male mice in comparison to cells derived from their wild-type counterparts...
July 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28703806/inhibition-of-autophagy-as-a-treatment-strategy-for-p53-wild-type-acute-myeloid-leukemia
#17
Hendrik Folkerts, Susan Hilgendorf, Albertus T J Wierenga, Jennifer Jaques, André B Mulder, Paul J Coffer, Jan Jacob Schuringa, Edo Vellenga
Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34(+) AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53(mut)), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53(R273H)...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703746/cudraflavone-c-induces-apoptosis-of-a375-s2-melanoma-cells-through-mitochondrial-ros-production-and-mapk-activation
#18
Chiang-Wen Lee, Feng-Lin Yen, Horng-Huey Ko, Shu-Yu Li, Yao-Chang Chiang, Ming-Hsueh Lee, Ming-Horng Tsai, Lee-Fen Hsu
Melanoma is the most malignant form of skin cancer and is associated with a very poor prognosis. The aim of this study was to evaluate the apoptotic effects of cudraflavone C on A375.S2 melanoma cells and to determine the underlying mechanisms involved in apoptosis. Cell viability was determined using the MTT and real-time cytotoxicity assays. Flow cytometric evaluation of apoptosis was performed after staining the cells with Annexin V-FITC and propidium iodide. The mitochondrial membrane potential was evaluated using the JC-1 assay...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28698505/retraction-zhang-k-et-al-knockdown-of-snail-sensitizes-pancreatic-cancer-cells-to-chemotherapeutic-agents-and-irradiation-int-j-mol-sci-2010-11-4891-4904-doi-10-3390-ijms11124891-and-zhang-k-et-al-rna-interference-targeting-slug-increases-cholangiocarcinoma
#19
https://www.readbyqxmd.com/read/28696204/ltp-and-memory-impairment-caused-by-extracellular-a%C3%AE-and-tau-oligomers-is-app-dependent
#20
Daniela Puzzo, Roberto Piacentini, Mauro Fá, Walter Gulisano, Domenica D Li Puma, Agnes Staniszewski, Hong Zhang, Maria Rosaria Tropea, Sara Cocco, Agostino Palmeri, Paul Fraser, Luciano D'Adamio, Claudio Grassi, Ottavio Arancio
The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP...
July 11, 2017: ELife
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