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https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#1
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28531161/development-of-optimized-inhibitor-rnas-allowing-multisite-targeting-of-the-hcv-genome
#2
Cristina Romero-López, Thomas Lahlali, Beatriz Berzal-Herranz, Alfredo Berzal-Herranz
Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs...
May 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#3
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28527529/image-guided-ablation-of-renal-cell-carcinoma
#4
REVIEW
T M Wah
This review article aims to provide an overview of image-guided ablation of renal cell carcinoma (RCC) since it was first introduced in 1998. This will cover the background and rationale behind its development; an overview of the evidence for current thermal technology, such as heat-based, e.g., radiofrequency ablation (RFA), microwave ablation (MWA), and cold-based energies, e.g., cryoablation used; and summarise the published evidence regarding its treatment efficacy and oncological outcome. In addition, it aims to provide an insight into the potential role of the new non-thermal ablative technology, e...
May 17, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28522639/definition-of-a-rack1-interaction-network-in-drosophila-melanogaster-using-swath-ms
#5
Lauriane Kuhn, Karim Majzoub, Evelyne Einhorn, Johana Chicher, Pompon Julien, Jean-Luc Imler, Philippe Hammann, Carine Meignin
Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins...
May 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28521305/bushen-yizhi-formula-ameliorates-cognitive-dysfunction-through-sirt1-er-stress-pathway-in-samp8-mice
#6
Shi-Jie Zhang, Ting-Ting Xu, Lin Li, Yu-Min Xu, Zi-Ling Qu, Xin-Chen Wang, Shui-Qing Huang, Yi Luo, Na-Chuan Luo, Ping Lu, Ya-Fei Shi, Xin Yang, Qi Wang
The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516273/a-comparative-study-of-ablation-boundary-sharpness-after-percutaneous-radiofrequency-cryo-microwave-and-irreversible-electroporation-ablation-in-normal-swine-liver-and-kidneys
#7
Francois H Cornelis, Jeremy C Durack, Simon Y Kimm, Thomas Wimmer, Jonathan A Coleman, Stephen B Solomon, Govindarajan Srimathveeravalli
PURPOSE: To compare ablation boundary sharpness after percutaneous radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA) and irreversible electroporation (IRE) ablation in normal swine liver and kidney. MATERIALS AND METHODS: Percutaneous CT-guided RFA (n = 5), CA (n = 5), MWA (n = 5) and IRE (n = 5) were performed in the liver and kidney of four Yorkshire pigs. Parameters were chosen to produce ablations 2-3 cm in diameter with a single ablation probe...
May 17, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28508759/mri-trus-fusion-for-electrode-positioning-during-irreversible-electroporation-for-treatment-of-prostate-cancer
#8
Alexander D J Baur, Federico Collettini, Judith Enders, Andreas Maxeiner, Vera Schreiter, Carsten Stephan, Bernhard Gebauer, Bernd Hamm, Thomas Fischer
We aimed to introduce an approach for image-guided positioning of electrodes for irreversible electroporation (IRE) in patients with prostate cancer using a magnetic resonance imaging-transrectal ultrasonography (MRI-TRUS) fusion technique. In 10 consecutive patients with biopsy-proven Gleason score ≤3+4 prostate cancer, 19 G electrodes were inserted into the prostate using a transperineal access. Magnetic resonance images of the prostate acquired before IRE were fused with transrectal ultrasound images acquired during IRE...
May 15, 2017: Diagnostic and Interventional Radiology: Official Journal of the Turkish Society of Radiology
https://www.readbyqxmd.com/read/28506570/the-local-liver-ablation-with-pulsed-electric-field-stimulate-systemic-immune-reaction-against-hepatocellular-carcinoma-hcc-with-time-dependent-cytokine-profile
#9
Xinhua Chen, Zhigang Ren, Shengyong Yin, Yuning Xu, Danjing Guo, Haiyang Xie, Lin Zhou, Liming Wu, Jianwen Jiang, Hongchun Li, Junhui Sun, Shusen Zheng
AIM: How irreversible electroporation (IRE) affect immune status is still kept unknown. This preclinical study is to investigate its local and systemic immune reaction both on tumor-bearing and tumor free animals. METHODS: Liver ablation was performed by a standard IRE instrument and proposal. Altogether 57 tumor bearing mice and 10 tumor-free porcine livers were ablated. The reaction of survival, radiology image, pathologically and immunologically were followed up...
May 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28503258/feasibility-of-pancreatectomy-following-high-dose-proton-therapy-for-unresectable-pancreatic-cancer
#10
Kathryn E Hitchcock, R Charles Nichols, Christopher G Morris, Debashish Bose, Steven J Hughes, John A Stauffer, Scott A Celinski, Elizabeth A Johnson, Robert A Zaiden, Nancy P Mendenhall, Michael S Rutenberg
AIM: To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic adenocarcinoma. METHODS: From April 2010 to September 2013, 15 patients with initially unresectable pancreatic cancer were treated with proton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy (RBE) to the gross disease and 1 patient received 50.40 Gy (RBE) to high-risk nodal targets...
April 27, 2017: World Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28500443/genome-characterization-of-a-novel-megrivirus-related-avian-picornavirus-from-a-carnivorous-wild-bird-western-marsh-harrier-circus-aeruginosus
#11
Ákos Boros, Péter Pankovics, Róbert Mátics, Ádám Adonyi, Nóra Bolba, Tung Gia Phan, Eric Delwart, Gábor Reuter
In this study, the complete genome of a novel picornavirus called harrier picornavirus 1 (HaPV-1) strain harrier/MR-01/HUN/2014 (KY488458) was sequenced and analysed from a cloacal sample of a threatened, carnivorous wild bird, western marsh harrier (Circus aeruginosus). HaPV-1 was detectable from 2 of the 3 samples from harriers. HaPV-1 is phylogenetically related to megriviruses (genus Megrivirus) from domestic chicken, turkey and duck, showing a similar genome organization pattern; it also has an avian picornavirus-like "Unit A" motif in the 3' UTR...
May 12, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28493544/recurrence-patterns-following-irreversible-electroporation-for-hepatic-malignancies
#12
Russell C Langan, Debra A Goldman, Michael I D'Angelica, Ronald P DeMatteo, Peter J Allen, Vinod P Balachandran, William R Jarnagin, T Peter Kingham
BACKGROUND: Irreversible electroporation (IRE) has emerged as a novel, safe ablative therapy for peri-vascular lesions. However, there remains a paucity of data on long-term outcomes. METHODS: We identified patients who underwent open IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local ablation-zone recurrence (LR) was determined by cross-sectional imaging. Cumulative incidence (CumI) of LR was calculated and a competing risks regression assessed factors associated with LR...
May 11, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28492549/enhanced-neuroprotective-efficacy-of-bone-marrow-mesenchymal-stem-cells-co-overexpressing-bdnf-and-vegf-in-a-rat-model-of-cardiac-arrest-induced-global-cerebral-ischemia
#13
Lili Zhou, Qingming Lin, Peng Wang, Lan Yao, Kahong Leong, Zhiqun Tan, Zitong Huang
Cardiac arrest-induced global cerebral ischemia injury (CA-GCII) usually leads to a poor neurological outcome without an effective treatment. Bone marrow-derived mesenchymal stem cells (BMMSCs) may provide a potential cell-based therapy against neurologic disorders through induction of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). To optimize the neuroprotective efficacy of BMMSCs further, in this study we have derived BMMSCs, which co-overexpress both BDNF and VEGF, and tested them for the treatment of CA-GCII in a rat model...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28492356/high-frequency-irreversible-electroporation-safety-and-efficacy-of-next-generation-irreversible-electroporation-adjacent-to-critical-hepatic-structures
#14
Imran A Siddiqui, Russell C Kirks, Eduardo L Latouche, Matthew R DeWitt, Jacob H Swet, Erin H Baker, Dionisios Vrochides, David A Iannitti, Rafael V Davalos, Iain H McKillop
Irreversible electroporation (IRE) is a nonthermal ablation modality employed to induce in situ tissue-cell death. This study sought to evaluate the efficacy of a novel high-frequency IRE (H-FIRE) system to perform hepatic ablations across, or adjacent to, critical vascular and biliary structures. Using ultrasound guidance H-FIRE electrodes were placed across, or adjacent to, portal pedicels, hepatic veins, or the gall bladder in a porcine model. H-FIRE pulses were delivered (2250 V, 2-5-2 pulse configuration) in the absence of cardiac synchronization or intraoperative paralytics...
June 2017: Surgical Innovation
https://www.readbyqxmd.com/read/28481001/transgenic-scs-expressing-gdnf-ires-dsred-impair-nerve-regeneration-within-acellular-nerve-allografts
#15
Xueping Ee, Ying Yan, Daniel A Hunter, Lauren Schellhardt, Shelly E Sakiyama-Elbert, Susan E Mackinnon, Matthew D Wood
Providing temporally regulated glial cell line-derived neurotrophic factor (GDNF) to injured nerve can promote robust axon regeneration. However, it is poorly understood why providing highly elevated levels of GDNF to nerve can lead to axon entrapment in the zone containing elevated GDNF. This limited understanding represents an obstacle to the translation of GDNF therapies to treat nerve injuries clinically. Here, we investigated how transgenic Schwann cells (SCs) overexpressing GDNF-IRES-DsRed impact nerve regeneration...
May 8, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28477079/-irreversible-electroporation-ire-a%C3%A2-minimally-invasive-therapeutic-option-in-prostate-cancer
#16
REVIEW
P Wiggermann, K Brünn, W Bäumler
CLINICAL PROBLEM: Prostate cancer is one of the most common malignant diseases in older men. As such, screening and early detection are of crucial importance. STANDARD TREATMENT: The standard management of prostate cancer includes radical prostatectomy, radiation therapy, or hormonal therapy. These standard therapies yield excellent oncologic results, but also produce significant side effects. In cases of low-risk prostate cancer, these therapies might result in over-treatment; for this reason, active surveillance has been introduced...
May 5, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28472856/multiple-cell-types-form-the-vip-amacrine-cell-population
#17
Luis Pérez de Sevilla Müller, Alexander Solomon, Kristopher Sheets, Hinekura Hapukino, Allen Rodriguez, Nicholas C Brecha
Amacrine cells are a heterogeneous group of interneurons that form microcircuits with bipolar, amacrine and ganglion cells to process visual information in the inner retina. This study has characterized the morphology, neurochemistry and major cell types of a VIP-ires-Cre amacrine cell population. VIP-tdTomato and -Confetti (Brainbow2.1) mouse lines were generated by crossing a VIP-ires-Cre line with either a Cre-dependent tdTomato or Brainbow2.1 reporter line. Retinal sections and whole-mounts were evaluated by quantitative, immunohistochemical and intracellular labeling approaches...
May 4, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28470866/cho-cells-engineered-for-fluorescence-read-out-of-cell-cycle-and-growth-rate-in-real-time
#18
Grischa Fuge, Yaeseong Hong, Kristoffer Riecken, An-Ping Zeng, Uwe Jandt
For efficient production of recombinant proteins by mammalian cells in a bioreactor, optimal growth rates are required and represent the most important process parameter. We present the first successful attempt to monitor the growth behavior and cell cycle state of a mammalian production relevant cell line under bioreactor cultivation conditions up to 1.2 l, utilizing a fluorescent read-out without the need of additional staining or marking. For this purpose, we developed two new production relevant cell line derivatives (CHO-K1 FUCCI CM & CHO-K1 FUCCI CN) and corresponding analytical methods...
May 4, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28470395/irreversible-electroporation-to-treat-malignant-tumor-recurrences-within-the-pelvic-cavity-a-case-series
#19
L G P H Vroomen, H J Scheffer, M C A M Melenhorst, N van Grieken, M P van den Tol, M R Meijerink
OBJECTIVE: To describe the initial experience with irreversible electroporation (IRE) to treat pelvic tumor recurrences. METHODS: A retrospective single-center analysis was performed. Adverse events were recorded using Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Clinical outcome was determined using pain- and general- symptom assessment, including Seddon's peripheral nerve injury (PNI) types. Radiological outcome was evaluated by comparing baseline with three-month 18F-FDG PET-CT follow-up...
May 3, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28466036/frequency-of-nucleotide-sequence-variations-in-the-internal-ribosome-entry-site-region-of-hepatitis-c-virus-rna-isolated-from-responding-and-non-responding-patients-with-hepatitis-c-virus-genotype-3-infection
#20
Anzar Ashraf, Anita Chakravarti, Priyamvada Roy, Premashish Kar, Oves Siddiqui
Located within 5' untranslated region of HCV RNA is internal ribosome entry site (IRES) which directs cap-independent translation of viral polyprotein. Mutations in IRES sequence have been shown to cause changes in efficiency of protein translation in vitro in few instances. No study has been done to investigate association between frequency of nucleotide sequence variations in IRES region of HCV-3 RNA and response to pegylated interferon-α plus ribavirin therapy. Hence, this study was planned to analyze relationship between frequency of nucleotide sequence variations of HCV-3 IRES region and response to therapy...
September 2016: Virusdisease
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