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https://www.readbyqxmd.com/read/28331845/irreversible-electroporation-of-hepatocellular-carcinoma-patient-selection-and-perspectives
#1
REVIEW
Asha Zimmerman, David Grand, Kevin P Charpentier
Irreversible electroporation (IRE) is a novel form of tissue ablation that uses high-current electrical pulses to induce pore formation of the cell lipid bilayer, leading to cell death. The safety of IRE for ablation of hepatocellular carcinoma (HCC) has been established. Outcome data for ablation of HCC by IRE are limited, but early results are encouraging and suggest equivalency to the outcomes obtained for thermal ablation for appropriately selected, small (<3 cm) tumors. Long-term oncologic efficacy and histopathologic response data have not been published, and therefore, application of IRE for the treatment of HCC should still be viewed with caution...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28330852/a-controlled-release-mitochondrial-protonophore-reverses-hypertriglyceridemia-nonalcoholic-steatohepatitis-and-diabetes-in-lipodystrophic-mice
#2
Abudukadier Abulizi, Rachel J Perry, João Paulo G Camporez, Michael J Jurczak, Kitt Falk Petersen, Patricia Aspichueta, Gerald I Shulman
Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28327623/long-term-effectiveness-of-irreversible-electroporation-in-a-murine-model-of-colorectal-liver-metastasis
#3
P Sánchez-Velázquez, Q Castellví, A Villanueva, M Iglesias, R Quesada, C Pañella, M Cáceres, D Dorcaratto, A Andaluz, X Moll, J M Burdío, L Grande, A Ivorra, F Burdío
Irreversible electroporation (IRE) has recently gained in popularity as an ablative technique, however little is known about its oncological long-term outcomes. To determine the long-time survival of animals treated with a high dose of IRE and which histological changes it induces in tumoral tissue, IRE ablation was performed in forty-six athymic-nude mice with KM12C tumors implanted in the liver by applying electric current with different voltages (2000 V/cm, 1000 V/cm). The tumors were allowed to continue to grow until the animals reached the end-point criteria...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322930/engineered-domain-swapping-indicates-context-dependent-functional-role-of-rna-g-quadruplexes
#4
Debmalya Bhattacharyya, Mark J Morris, Prakash Kharel, Gayan Mirihana Arachchilage, Katy M Fedeli, Soumitra Basu
RNA domain swapping typically demonstrates conservation of the native function of the domain in a non-native context. In contrast, we employed RNA engineering to demonstrate deviation of G-quadruplex (GQ) function that is contingent upon its context dependent location, which is opposite to their native functional role. Known translation repressing RNA GQs were engineered into human VEGF IRES A replacing the endogenous GQ domain essential for translation. Alternatively, the translation inhibitory GQ motif within the 5'-UTR of MT3-MMP mRNA was replaced with two known GQ motifs that are essential for translation...
March 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#5
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28314951/relaxin-3-rxfp3-signalling-in-mouse-hypothalamus-no-effect-of-rxfp3-activation-on-corticosterone-despite-reduced-presynaptic-excitatory-input-onto-paraventricular-crh-neurons-in-vitro
#6
C Zhang, D V Baimoukhametova, C M Smith, J S Bains, Andrew L Gundlach
Relaxin-3/RXFP3 signalling is proposed to be involved in the neuromodulatory control of arousal- and stress-related neural circuits. Furthermore, previous studies in rats have led to the proposal that relaxin-3/RXFP3 signalling is associated with activation of the hypothalamic-pituitary-adrenal axis, but direct evidence for RXFP3-related actions on the activity of hypothalamic corticotropin-releasing hormone (CRH) neurons is lacking. In this study, we investigated characteristics of the relaxin-3/RXFP3 system in mouse hypothalamus...
March 17, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28288210/depletion-of-neat1-lncrna-attenuates-nucleolar-stress-by-releasing-sequestered-p54nrb-and-psf-to-facilitate-c-myc-translation
#7
Wen Shen, Xue-Hai Liang, Hong Sun, Cheryl L De Hoyos, Stanley T Crooke
Altered expression of NEAT1, the architectural long non-coding RNA (lncRNA) of nuclear paraspeckles, has been reported during tumorigenesis, as well as under various cellular stress conditions. Here we report that the depletion of NEAT1 lncRNA alleviates nucleolar stress during RNAP I inhibition through releasing sequestered P54nrb and PSF to facilitate the IRES-dependent translation of c-Myc. RNAP I inhibitor CX5461 disrupts the SL1-rDNA interaction and induces nucleolar disruption, demonstrated by the accumulation of fibrillarin-containing nucleoplasmic foci and nucleolar clearance of ribosomal proteins in HeLa cells...
2017: PloS One
https://www.readbyqxmd.com/read/28286905/explaining-response-repetition-effects-in-task-switching-evidence-from-switching-cue-modality-suggests-episodic-binding-and-response-inhibition
#8
Iring Koch, Christian Frings, Stefanie Schuch
Task switching studies revealed that the usual response-repetition benefit is abolished and often reversed if the task switches. According to episodic binding accounts, performing responses strengthens task-specific bindings, leading to response-repetition benefits in task repetitions, whereas such bindings can lead to interference (i.e., costs of "unbinding") in task switches. An alternative account assumes that responses are generally inhibited after execution but that the assumed sequential carryover of response inhibition is overcompensated by positive priming of stimulus category in task repetitions (resulting in a positive net effect in response-repetition conditions)...
March 12, 2017: Psychological Research
https://www.readbyqxmd.com/read/28285364/hierarchical-task-organization-in-dual-tasks-evidence-for-higher-level-task-representations
#9
Patricia Hirsch, Sophie Nolden, Andrea M Philipp, Iring Koch
To examine whether hierarchical higher level task representations comprising the task sets of Task 1 (T1) and Task 2 (T2) are activated within each trial in dual-task situations, we combined the psychological refractory period (PRP) paradigm with the task-pair switching logic (Hirsch et al. 2017). In Experiment 1, in which subjects switched between task-pairs including a varying T1 and a constant T2, we found a PRP effect (i.e., worse performance with short stimulus onset asynchrony [SOA] than with long SOA) and task-pair switch costs in T1 and T2 (impaired performance in task-pair switches compared to task-pair repetitions)...
March 11, 2017: Psychological Research
https://www.readbyqxmd.com/read/28274634/assessment-of-new-triplet-forming-artificial-nucleobases-as-rna-ligands-directed-towards-hcv-ires-iiid-loop
#10
Mauro Safir Filho, Anthony R Martin, Rachid Benhida
We report the synthesis of two new artificial nucleobase scaffolds, 1 and 2, featuring adequate hydrogen bonding donors and acceptors for the molecular recognition of U:A and C:G base pairs, respectively. The tethering of these structures to various amino acids and the assessment of these artificial nucleobase-amino acid conjugates as RNA ligands against a model of HCV IRES IIId domain are also reported. Compound 1e displayed the highest affinity (Kd twice lower than neomycin - control). Moreover, it appears that this interaction is enthalpically and entropically favored...
February 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28274313/-establishment-of-esophageal-squamous-carcinoma-cell-lines-stably-over-expressing-llgl2
#11
Qiong Hu, Fu'an Xie, Xiaoqian Hong, Kuancan Liu
Objective To prepare a lentiviral vector expressing LLGL2 and establish KYSE450 and TE-1 cell lines for the stable expression of LLGL2. Methods The full-length LLGL2 sequence was amplified by high-fidelity PCR, and then it was inserted into pCDH-CMV-IRES-GFP-EF1-Puro vectors. The recombinant plasmid was confirmed by double enzyme digestion and sequencing. After co-infection of pCDH-CMV-LLGL2-IRES- GFP-EF1-Puro with vesicular stomatitis virus glycoprotein (VSVG) and PHR into HEK293T cells, the lentivirus was harvested and used for infecting esophageal squamous cell carcinoma cell lines including KYSE450 and TE-1 cells...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#12
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271030/high-fidelity-glucagon-creer-mouse-line-generated-by-crispr-cas9-assisted-gene-targeting
#13
Amanda M Ackermann, Jia Zhang, Aryel Heller, Anna Briker, Klaus H Kaestner
OBJECTIVE: α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28266600/percutaneous-irreversible-electroporation-long-term-survival-analysis-of-71-patients-with-inoperable-malignant-hepatic-tumors
#14
C Niessen, S Thumann, L Beyer, B Pregler, J Kramer, S Lang, A Teufel, E M Jung, C Stroszczynski, P Wiggermann
Aim of this retrospective analysis was to evaluate the survival times after percutaneous irreversible electroporation (IRE) in inoperable liver tumors not amenable to thermal ablation. 71 patients (14 females, 57 males, median age 63.5 ± 10.8 years) with 103 liver tumors were treated in 83 interventions using IRE (NanoKnife(®) system). The median tumor short-axis diameter was 1.9 cm (minimum 0.4 cm, maximum 4.5 cm). 35 patients had primary liver tumors and 36 patients had liver metastases. The Kaplan-Meier method was employed to calculate the survival rates, and the different groups were compared using multivariate log-rank and Wilcoxon tests...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265231/comparison-between-cryoablation-and-irreversible-electroporation-of-rabbit-livers-at-a-location-close-to-the-gallbladder
#15
Jianying Zeng, Zilin Qin, Liang Zhou, Gang Fang, Jibing Chen, Jialiang Li, Lizhi Niu, Bing Liang, Kecheng Xu
BACKGROUND: The ablation of liver tumors located close to the gallbladder is likely to lead to complications. The aim of this article is to compare the safety and efficacy of irreversible electroporation (IRE) and cryoablation in rabbit livers at a location close to the gallbladder. MATERIALS AND METHODS: We performed cryoablation (n = 12) and IRE (n = 12) of the area of the liver close to the gallbladder in 24 New Zealand white rabbits in order to ensure gallbladder damage...
March 1, 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/28261264/ferrous-iron-up-regulation-in-fibroblasts-of-patients-with-beta-propeller-protein-associated-neurodegeneration-bpan
#16
Rosaria Ingrassia, Maurizio Memo, Barbara Garavaglia
Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2)...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28260008/tauroursodeoxycholic-acid-inhibits-tnf-%C3%AE-induced-lipolysis-in-3t3-l1-adipocytes-via-the-ire-jnk-perilipin-a-signaling-pathway
#17
Wenyan Xia, Yu Zhou, Lijing Wang, Linxi Wang, Xiaoying Liu, Yichuan Lin, Qing Zhou, Jianqing Huang, Libin Liu
The present study investigated the effects of tauroursodeoxycholic acid (TUDCA) on the lipolytic action of tumor necrosis factor (TNF)-α in 3T3-L1 adipocytes. Following treatment with TNF‑α, cell viability was determined by MTT assay to select the optimum concentration and duration of TNF‑α treatment in 3T3‑L1 adipocytes. Intracellular lipid droplet dispersion and glycerin content in culture media were determined to evaluate the effect of TUDCA on TNF‑α‑induced lipolysis in 3T3‑L1 adipocytes...
February 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28254562/cb1-receptor-mediated-respiratory-depression-by-endocannabinoids
#18
András Iring, László Hricisák, Zoltán Benyó
Endocannabinoids (ECs) are bioactive lipid mediators acting on two distinct cannabinoid receptors (CB1 and CB2), which are ubiquitously expressed in many tissues including the respiratory system. Despite numerous experimental data showing that cannabinomimetics influence respiration, the role of endogenously produced ECs in respiratory control has not been verified yet. Pulse oximetry was used in the present study to directly measure changes in respiratory parameters during elevation of EC levels. The cannabinoid reuptake inhibitor AM-404 (10mgkg(-1), i...
February 22, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28253331/irreversible-electroporation-ablation-area-enhanced-by-synergistic-high-and-low-voltage-pulses
#19
Chenguo Yao, Yanpeng Lv, Shoulong Dong, Yajun Zhao, Hongmei Liu
Irreversible electroporation (IRE) produced by a pulsed electric field can ablate tissue. In this study, we achieved an enhancement in ablation area by using a combination of short high-voltage pulses (HVPs) to create a large electroporated area and long low-voltage pulses (LVPs) to ablate the electroporated area. The experiments were conducted in potato tuber slices. Slices were ablated with an array of four pairs of parallel steel electrodes using one of the following four electric pulse protocols: HVP, LVP, synergistic HVP+LVP (SHLVP) or LVP+HVP...
2017: PloS One
https://www.readbyqxmd.com/read/28242053/regulation-mechanisms-of-viral-ires-driven-translation
#20
REVIEW
Kuo-Ming Lee, Chi-Jene Chen, Shin-Ru Shih
Internal ribosome entry sites (IRESs) can be found in the mRNA of many viruses as well as in cellular genes involved in the stress response, cell cycle, and apoptosis. IRES-mediated translation can occur when dominant cap-dependent translation is inhibited, and viruses can take advantage of this to subvert host translation machinery. In this review, we focus on the four major types of IRES identified in RNA viruses, and outline their distinct structural properties and requirements of translational factors. We further discuss auxiliary host factors known as IRES trans-acting factors (ITAFs), which are involved in the modulation of optimal IRES activity...
February 24, 2017: Trends in Microbiology
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