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https://www.readbyqxmd.com/read/27894402/hsp90-inhibitor-enhances-anti-proliferative-and-apoptotic-effects-of-celecoxib-on-ht-29-colorectal-cancer-cells-via-increasing-bax-bcl-2-ratio
#1
A Mohammadi, M M Yaghoobi, A GholamhoseynianNajar, B Kalantari-Khandani, H Sharifi, M Saravani
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27878398/hsp90-is-a-promising-target-in-gemcitabine-and-5-fluorouracil-resistant-pancreatic-cancer
#2
Tarik Ghadban, Judith L Dibbern, Matthias Reeh, Jameel T Miro, Tung Y Tsui, Ulrich Wellner, Jakob R Izbicki, Cenap Güngör, Yogesh K Vashist
Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent client proteins of HSP90. HSP90 is a promising target since it interferes with many oncogenic signaling pathways simultaneously. The aim of this study was to evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to culture from patients being operated at our institution...
November 22, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27867076/the-dna-chaperone-hmgb1-potentiates-the-transcriptional-activity-of-rel1a-in-the-mosquito-aedes-aegypti
#3
Anderson de Mendonça Amarante, Natapong Jupatanakul, Isabel Caetano de Abreu da Silva, Vitor Coutinho Carneiro, Amanda Roberta Revoredo Vicentino, George Dimopolous, Octávio Augusto C Talyuli, Marcelo Rosado Fantappié
High Mobility Group protein 1 (HMGB1) is a non-histone, chromatin-associated nuclear protein that functions in regulating eukaryotic gene expression. We investigated the influence and mechanism of action of Aedes aegypti HMGB1 (AaHMGB1) on mosquito Rel1A-mediated transcription from target gene promoters. The DNA-binding domain (RHD) of AaRel1A was bacterially expressed and purified, and AaHMGB1 dramatically enhanced RHD binding to consensus NF-kB/Rel DNA response elements. Luciferase reporter analyses using a cecropin gene promoter showed that AaHMGB1 potentiates the transcriptional activity of AaRel1A in Aag-2 cells...
November 17, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27862436/redefining-the-phenotype-of-heat-shock-protein-90-hsp90-inhibitors
#4
Yao Wang, Yen Chin Koay, Shelli Renee McAlpine
Comparing the phenotypes produced when cells are treated with the Hsp90 inhibitors AUY922 or 17-AAG (classical inhibitors) to cells with Hsp90alpha knocked down reveals that the knockdown phenotype is unique from that produced by the inhibitors. Pull-down assays using classical inhibitors verify that these molecules do not bind to Hsp90 as their primary target. Classical inhibitors induce similar protein markers as other anti-cancer therapies Cisplatin and bortezomib, suggesting that AUY922 and 17-AAG act on targets other than Hsp90 and kill cells through multiple mechanisms...
November 8, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27829290/hsp90-inhibitors-in-the-context-of-heat-shock-and-the-unfolded-protein-response-effects-on-a-primary-canine-pulmonary-adenocarcinoma-cell-line
#5
Arin N Graner, Justin E Hellwinkel, Alex M Lencioni, Helen J Madsen, Tessa A Harland, Paul Marchando, Ger J Nguyen, Mary Wang, Laura M Russell, Lynne T Bemis, Thomas J Anchordoquy, Michael W Graner
BACKGROUND: Agents targeting HSP90 and GRP94 are seldom tested in stressed contexts such as heat shock (HS) or the unfolded protein response (UPR). Tumor stress often activates HSPs and the UPR as pro-survival mechanisms. This begs the question of stress effects on chemotherapeutic efficacy, particularly with drugs targeting chaperones such as HSP90 or GRP94. We tested the utility of several HSP90 inhibitors, including PU-H71 (targeting GRP94), on a primary canine lung cancer line under HS/UPR stress compared to control conditions...
November 9, 2016: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/27821014/novel-mutation-of-the-translation-initiation-codon-of-the-%C3%AE-1-globin-gene-atg-aag-or-hba1-c-2t-a
#6
John S Waye, Barry Eng, Meredith Hanna, Betty-Ann Hohenadel, Lisa Nakamura, Lynda Walker
We report two Italian-Canadian families with α(+)-thalassemia (α(+)-thal) trait caused by a novel mutation of the translation initiation codon of the α1-globin gene (ATG>AAG or HBA1:c.2T>A). This is the tenth reported α-thal mutation involving the translation initiation codon or the conserved Kozak consensus sequences of the HBA2 or HBA1 genes.
September 2016: Hemoglobin
https://www.readbyqxmd.com/read/27799473/ef-g-catalyzed-translocation-dynamics-in-the-presence-of-ribosomal-frameshifting-stimulatory-signals
#7
Hee-Kyung Kim, Ignacio Tinoco
Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA. Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin...
October 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27796344/antileukemic-scalarane-sesterterpenoids-and-meroditerpenoid-from-carteriospongia-phyllospongia-sp-induce-apoptosis-via-dual-inhibitory-effects-on-topoisomerase-ii-and-hsp90
#8
Kuei-Hung Lai, Yi-Chang Liu, Jui-Hsin Su, Mohamed El-Shazly, Chih-Fung Wu, Ying-Chi Du, Yu-Ming Hsu, Juan-Cheng Yang, Ming-Kai Weng, Chia-Hua Chou, Guan-Yu Chen, Yu-Cheng Chen, Mei-Chin Lu
Two new scalarane sesterterpenoids, 12β-(3'β-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12β-(3'β-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 μg/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase IIα expression...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27785538/cholinergic-pet-imaging-in-infections-and-inflammation-using-11-c-donepezil-and-18-f-feobv
#9
Nis Pedersen Jørgensen, Aage K O Alstrup, Frank V Mortensen, Karoline Knudsen, Steen Jakobsen, Line Bille Madsen, Dirk Bender, Peter Breining, Mikkel Steen Petersen, Mariane Høgsberg Schleimann, Frederik Dagnæs-Hansen, Lars C Gormsen, Per Borghammer
INTRODUCTION: Immune cells utilize acetylcholine as a paracrine-signaling molecule. Many white blood cells express components of the cholinergic signaling pathway, and these are up-regulated when immune cells are activated. However, in vivo molecular imaging of cholinergic signaling in the context of inflammation has not previously been investigated. METHODS: We performed positron emission tomography (PET) using the glucose analogue 18F-FDG, and 11C-donepezil and 18F-FEOBV, markers of acetylcholinesterase and the vesicular acetylcholine transporter, respectively...
October 26, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27760294/investigation-of-the-differential-capacitance-of-highly-ordered-pyrolytic-graphite-as-a-model-material-of-graphene
#10
Yuqin Zou, Alex S Walton, Ian A Kinloch, Robert A W Dryfe
A study of the differences between the capacitance of freshly exfoliated highly ordered pyrolytic graphite (HOPG, sample denoted FEG), HOPG aged in air (denoted AAG) and aged in an inert atmosphere (hereafter IAG) is presented in this work. The FEG is found to be more hydrophilic than AAG and IAG since the aqueous electrolyte contact angle (CA) increases from 61.7o to 72.5o and 81.8o after aging in Ar and air, respectively. Electrochemical impedance spectroscopy (EIS) shows the FEG has higher intrinsic capacitance (6...
October 19, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27760062/cognitive-interventions-and-nutritional-supplements-the-cins-trial-a-randomized-controlled-multicenter-trial-comparing-a-brief-intervention-with-additional-cognitive-behavioral-therapy-seal-oil-and-soy-oil-for-sick-listed-low-back-pain-patients
#11
Silje E Reme, Torill H Tveito, Anette Harris, Stein Atle Lie, Astrid Grasdal, Aage Indahl, Jens Ivar Brox, Tone Tangen, Eli Molde Hagen, Sigmund Gismervik, Arit Ødegård, Livar Fryland, Egil A Fors, Trudie Chalder, Hege R Eriksen
STUDY DESIGN: A randomized controlled trial. OBJECTIVE: The aim of this study was to evaluate whether a tailored and manualized cognitive behavior therapy (CBT) or nutritional supplements of seal oil and soy oil had any additional benefits over a brief cognitive intervention (BI) on return to work (RTW). SUMMARY OF BACKGROUND DATA: Brief intervention programs are clinically beneficial and cost-effective for patients with low back pain (LBP)...
October 15, 2016: Spine
https://www.readbyqxmd.com/read/27756228/drug-discovery-using-clinical-outcome-based-connectivity-mapping-application-to-ovarian-cancer
#12
Rama Raghavan, Stephen Hyter, Harsh B Pathak, Andrew K Godwin, Gottfried Konecny, Chen Wang, Ellen L Goode, Brooke L Fridley
BACKGROUND: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States (5 % of cancer deaths). The standard treatment for patients with advanced EOC is initial debulking surgery followed by carboplatin-paclitaxel combination chemotherapy. Unfortunately, with chemotherapy most patients relapse and die resulting in a five-year overall survival around 45 %. Thus, finding novel therapeutics for treating EOC is essential. Connectivity Mapping (CMAP) has been used widely in cancer drug discovery and generally has relied on cancer cell line gene expression and drug phenotype data...
October 19, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27751862/the-impella-cp-device-for-acute-mechanical-circulatory-support-in-refractory-cardiac-arrest
#13
Henrik Vase, Steffen Christensen, Aage Christiansen, Christian Juhl Therkelsen, Evald Høj Christiansen, Hans Eiskjær, Steen Hvidtfeldt Poulsen
INTRODUCTION: Mechanical circulatory support may be considered as a therapeutic option in selected patients with refractory cardiac arrest (rCA). Animal studies suggest a potential role for the Impella(®) left ventricular assist device in this setting, but so far no human data have been published. METHODS: Eight patients with rCA were treated with the Impella CP(®) device at our institution from November 2014 to October 2015. The Impella CP(®) was used at the discretion of the treating physicians in patients with rCA and pulseless electrical activity with presumed primary left ventricular failure...
October 14, 2016: Resuscitation
https://www.readbyqxmd.com/read/27709284/population-pharmacokinetic-pharmacodynamic-modeling-and-model-based-prediction-of-docetaxel-induced-neutropenia-in-japanese-patients-with-non-small-cell-lung-cancer
#14
Masato Fukae, Yoshimasa Shiraishi, Takeshi Hirota, Yuka Sasaki, Mika Yamahashi, Koichi Takayama, Yoichi Nakanishi, Ichiro Ieiri
PURPOSE: Docetaxel is used to treat many cancers, and neutropenia is the dose-limiting factor for its clinical use. A population pharmacokinetic-pharmacodynamic (PK-PD) model was introduced to predict the development of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer (NSCLC). METHODS: Forty-seven advanced or recurrent Japanese patients with NSCLC were enrolled. Patients received 50 or 60 mg/m(2) docetaxel as monotherapy, and blood samples for a PK analysis were collected up to 24 h after its infusion...
October 5, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27706767/bioinformatic-analyses-of-gras-genes-in-betula-kirghisorum-based-on-transcriptome-data
#15
C J Yang, G Y Li, Y L Cui
The transcriptomes of salt-stressed and unstressed Betula kirghisorum plants were analyzed using high throughput sequencing technology. A total of 52,239,804 and 51,772,998 clean reads were obtained from the two libraries, respectively, and de novo assembled into 60,545 all-unigenes. A total of 39,997 unigenes were annotated using public databases. Overall, 7206 genes were differentially expressed in unigenes and were involved in 127 pathways. Thirteen transcription factor families were identified in B. kirghisorum, including GRAS proteins, which are plant-specific transcription factors...
September 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27706601/pheno-morphological-variation-genetic-diversity-and-population-structure-of-tunisian-echinus-medic-medicago-ciliaris-l
#16
C Jabri, H Sbei, N Zitouna, N Trifi-Farah, A Zoghlami Khelil
Medicago ciliaris L., considered as a valuable genetic resource, is a good candidate for the improvement of marginal or degraded lands with low fertility or high salinity. In this study, the pheno-morphological and genetic diversity were investigated in 14 Tunisian populations of M. ciliaris for the first time. Fourteen morphological traits showed significant differentiation between populations and high levels of diversity. Two amplified fragment length polymorphism primer combinations (E-AGC/M-CAA; E-AAG/M-CTG) were analyzed using an automated capillary electrophoresis system...
August 26, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27698830/17aag-induced-internalisation-of-her2-specific-affibody-molecules
#17
Lovisa Göstring, Sture Lindegren, Lars Gedda
The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17-AAG) is known to induce internalisation and degradation of the otherwise internalisation-resistant human epidermal growth factor receptor 2 (HER2) receptor. In the present study, 17-AAG was used to increase internalisation of the HER2-specific Affibody molecule ABY-025. The cellular redistribution of halogen-labelled (211)At-ABY-025 and radiometal-labelled (111)In-ABY-025 following treatment with 17-AAG was studied. 17-AAG treatment of SKOV-3 human ovarian carcinoma and SKBR-3 human breast carcinoma cells to some extent shifted the localisation of (111)In-ABY-025 from the cell surface to intracellular compartments in the two cell lines...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27698084/aag-hypoxanthine-dna-glycosylase-is-synthesized-in-the-forespore-compartment-and-involved-in-counteracting-the-genotoxic-and-mutagenic-effects-of-hypoxanthine-and-alkylated-bases-in-dna-during-bacillus-subtilis-sporulation
#18
Víctor M Ayala-García, Luz I Valenzuela-García, Peter Setlow, Mario Pedraza-Reyes
: Aag from Bacillus subtilis has been implicated in in vitro removal of hypoxanthine and alkylated bases from DNA. The regulation of expression of aag in B. subtilis and the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptional aag-lacZ fusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably, aag-lacZ expression was higher inside the forespore than in the mother cell compartment, and this expression was abolished in a sigG-deficient background, suggesting a forespore-specific mechanism of aag transcription...
December 15, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27690420/new-broad-spectrum-antibacterial-amphiphilic-aminoglycosides-active-against-resistant-bacteria-from-neamine-derivatives-to-smaller-neosamine-analogues
#19
Louis Zimmermann, Indrajit Das, Jérôme Désiré, Guillaume Sautrey, Vinicius Barros R S, Micheline El Khoury, Marie-Paule Mingeot-Leclercq, Jean-Luc Decout
Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection of resistant bacteria. Recently, conjugation of lipophilic groups to AGs generated a novel class of potent antibacterial amphiphilic aminoglycosides (AAGs) with significant improved activities against various sensitive and resistant bacterial strains...
October 3, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27677730/no-evidence-that-genetic-variation-in-the-myeloid-derived-suppressor-cell-pathway-influences-ovarian-cancer-survival
#20
Lara E Sucheston-Campbell, Rikki Cannioto, Alyssa I Clay, John Lewis Etter, Kevin H Eng, Song Liu, Sebastiano Battaglia, Qiang Hu, J Brian Szender, Albina Minlikeeva, Janine Joseph, Paul Mayor, Scott I Abrams, Brahm Segal, Paul K Wallace, Kah Teong Soh, Emese Z Zsiros, Hoda Anton-Culver, Elisa V Bandera, Matthias W Beckmann, Andrew Berchuck, Line Bjørge, Amanda Bruegl, Ian G Campbell, Shawn Patrice Campbell, Georgia Chenevix-Trench, Daniel Cramer, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Brenda Diergaarde, Thilo Doerk, Jennifer A Doherty, Andreas du Bois, Diana Eccles, Svend Aage Engelholm, Peter A Fasching, Simon A Gayther, Aleksandra Gentry-Maharaj, Rosalind M Glasspool, Marc T Goodman, Jacek Gronwald, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemmanns, Claus Hogdall, Estrid V S Høgdall, Tomasz Huzarski, Allan Jensen, Sharon E Johnatty, Audrey Jung, Beth Karlan, Rüdiger Klapdor, Tomasz Kluz, Bozena Konopka, Susanne Krüger Kjær, Jolanta Kupryjanczyk, Diether Lambrechts, Jenny Lester, Jan Lubiński, Douglas A Levine, Lene Lundvall, Valerie McGuire, Iain A McNeish, Usha Menon, Francesmary Modugno, Roberta B Ness, Sandra Orsulic, James Paul, Celeste Leigh Pearce, Tanja Pejovic, Paul Pharoah, Susan J Ramus, Joseph Rothstein, Mary Anne Rossing, Matthias Rübner, Joellen M Schildkraut, Barbara Schmalfeldt, Ira Schwaab, Nadeem Siddiqui, Weiva Sieh, Piotr Sobiczewski, Honglin Song, Kathryn L Terry, Els Van Nieuwenhuysen, Adriaan Vanderstichele, Ignace Vergote, Christine S Walsh, Penelope M Webb, Nicolas Wentzensen, Alice S Whittemore, Anna H Wu, Argyrios Ziogas, Kunle Odunsi, Jenny Chang-Claude, Ellen L Goode, Kirsten B Moysich
BACKGROUND: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immune suppressive/pro-tumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be one prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. METHODS: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC...
September 27, 2016: Cancer Epidemiology, Biomarkers & Prevention
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