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https://www.readbyqxmd.com/read/28829490/effect-of-alk-inhibitors-in-the-treatment-of-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#1
G Li, W-R Dai, F-C Shao
OBJECTIVE: Lung cancer is the leading cause of cancer-related mortality. Over 80% of all lung cancer cases are non-small-cell lung cancer (NSCLC) and approximately 5% of NSCLC patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4 (EML4). NSCLC patients with positive ALK-EML4 gene fusion are highly sensitive to ALK-inhibitors. While the efficacy of the ALK-inhibitors in the treatment of NSCLC has been consistently reported, a limited number of randomized, large-scale clinical trials have been reported...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28829410/live-imaging-of-primary-cerebral-cortex-cells-using-a-2d-culture-system
#2
Bruna Soares Landeira, Jéssica Alves de Medeiros Araújo, Timm Schroeder, Ulrich Müller, Marcos R Costa
During cerebral cortex development, progenitor cells undergo several rounds of symmetric and asymmetric cell divisions to generate new progenitors or postmitotic neurons. Later, some progenitors switch to a gliogenic fate, adding to the astrocyte and oligodendrocyte populations. Using time-lapse video-microscopy of primary cerebral cortex cell cultures, it is possible to study the cellular and molecular mechanisms controlling the mode of cell division and cell cycle parameters of progenitor cells. Similarly, the fate of postmitotic cells can be examined using cell-specific fluorescent reporter proteins or post-imaging immunocytochemistry...
August 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28829360/principal-aspects-regarding-the-maintenance-of-mammalian-mitochondrial-genome-integrity
#3
REVIEW
Panagiotis V S Vasileiou, Iordanis Mourouzis, Constantinos Pantos
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28829353/chemokines-as-a-conductor-of-bone-marrow-microenvironment-in-chronic-myeloid-leukemia
#4
REVIEW
Naofumi Mukaida, Yamato Tanabe, Tomohisa Baba
All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28828991/a-virtual-screening-approach-for-the-identificationof-high-affinity-small-molecules-targeting-bcr-abl1-inhibitors-for-the-treatment-of-chronic-myeloid-leukemia
#5
Saphy Sharda, Palash Sarmandal, Srinivas Bandaru, Pravin Patil, Ruchi Shukla, Amrita Jain, Anudeep Sharma, Tanmay Vyas, Tajamul Hussain, Anuraj Nayarisseri
CML originates due to reciprocal translocation in Philadelphia chromosome leading to formation of fusion product BCR-ABL which constitutively activates tyrosine kinase signaling pathways eventually abnormal proliferation of granulocytic cells. As a therapeutic strategy, BCR-ABL inhibitors have been clinically approved which terminates its phosphorylation activity and retards cancer progression. However,number of patients develops resistance to inhibitors which demand for discovery of new inhibitors. Given the drawbacks of present inhibitors, by high throughput virtual screening approaches, present study pursues to identify high affinity compounds targeting BCR-ABL1 anticipated to have safer pharmacological profiles...
August 21, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28828662/in-vivo-tracking-of-extracellular-vesicles-in-mice-using-fusion-protein-comprising-lactadherin-and-gaussia-luciferase
#6
Yuki Takahashi, Makiya Nishikawa, Yoshinobu Takakura
Extracellular vesicles (EVs) are cell-derived vesicles comprising a lipid bilayer and are found in body fluids, such as blood, sweat, and urine. As EVs, especially exosomes, function as endogenous intercellular delivery tools, their roles in various biological events have been extensively investigated. In addition, they are expected to become safe and effective drug delivery systems (DDS) because of their intrinsic nature. In the development of EV-based DDS, as well as in the investigation of the biological functions of EVs, it is important to analyze the in vivo behavior of EVs by tracking them...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28828644/red-blood-cells-a-source-of-extracellular-vesicles
#7
Winston Patrick Kuo, John C Tigges, Vasilis Toxavidis, Ionita Ghiran
During their lifetime, like all other cell types, red blood cells (RBCs) release both exosomes and plasma membrane derived EVs (ectosomes). RBC exosomes are formed only during the development of RBCs in bone marrow, and are released following the fusion of microvesicular bodies (MVB) with the plasma membrane. On the other hand, RBC EVs are generated during normal aging of RBCs in circulation by budding of the plasma membrane due to complement -mediated calcium influx, followed by vesicle shedding. This makes red blood cells and stored red cells a reliable source of EVs for basic and clinical research...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28827692/improvement-of-pharmacokinetic-profile-of-trail-via-trimer-tag-enhances-its-antitumor-activity-in-vivo
#8
Haipeng Liu, Danmei Su, Jinlong Zhang, Shuaishuai Ge, Youwei Li, Fei Wang, Michel Gravel, Anne Roulston, Qin Song, Wei Xu, Joshua G Liang, Gordon Shore, Xiaodong Wang, Peng Liang
TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) has long been considered a tantalizing target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors DR4 or DR5. Despite initial promise, both recombinant human TRAIL (native TRAIL) and dimeric DR4/DR5 agonist monoclonal antibodies (mAbs) failed in multiple human clinical trials. Here we show that in-frame fusion of human C-propeptide of α1(I) collagen (Trimer-Tag) to the C-terminus of mature human TRAIL leads to a disulfide bond-linked homotrimer which can be expressed at high levels as a secreted protein from CHO cells...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827408/hematopoietic-stem-cell-involvement-in-bcr-abl1-positive-all-as-potential-mechanism-of-resistance-to-blinatumomab-therapy
#9
Inga Nagel, Marius Bartels, Johannes Duell, Hans-Heinrich Oberg, Sandra Ussat, Henrike Bruckmueller, Oliver Ottmann, Heike Pfeifer, Heiko Trautmann, Nicola Gökbuget, Almuth Caliebe, Dieter Kabelitz, Michael Kneba, Heinz-August Horst, Dieter Hoelzer, Max S Topp, Ingolf Cascorbi, Reiner Siebert, Monika Brüggemann
The bispecific T-cell engager blinatumomab targeting CD19 can induce complete remission in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, some patients ultimately relapse with loss of CD19-antigen on leukemic cells which has been established as a novel escape mechanism to CD19-specific immunotherapies. Here, we provide evidence that CD19-negative relapse after CD19-directed therapy in BCP-ALL may be due to selection of preexisting CD19-negative malignant progenitor cells...
August 21, 2017: Blood
https://www.readbyqxmd.com/read/28827407/arl8b-is-required-for-lysosomal-degradation-of-maternal-proteins-in-the-visceral-yolk-sac-endoderm-of-mouse-embryos
#10
Miho Oka, Keisuke Hashimoto, Yoshifumi Yamaguchi, Shin-Ichiro Saitoh, Yuki Sugiura, Yuji Motoi, Kurara Honda, Yorifumi Kikko, Shinya Ohata, Makoto Suematsu, Masayuki Miura, Kensuke Miyake, Toshiaki Katada, Kenji Kontani
The small GTPase Arl8b localizes primarily to lysosomes and is involved in lysosomal motility and fusion. Here, we show that Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm (VYSE), an apical cell layer of the visceral yolk sac, of mouse embryos. The VYSE actively takes up maternal materials from uterine fluid and degrades them in lysosomes to provide breakdown products to the embryo as energy sources. Arl8b gene-trap mice (Arl8b(-/-) ) displayed decreased early embryo body size...
August 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28827281/munc18a-clusters-snare-bearing-liposomes-prior-to-trans-snare-zippering
#11
Matthew Grant Arnold, Pratikshya Adhikari, Baobin Kang, Hao Xu
Sec1-Munc18 (SM) proteins cooperate with SNAREs {SNAP [soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein] receptors} to mediate membrane fusion in eukaryotic cells. Studies of Munc18a/Munc18-1/Stxbp1 in neurotransmission suggest that SM proteins accelerate fusion kinetics primarily by activating the partially zippered trans-SNARE complex. However, accumulating evidence has argued for additional roles for SM proteins in earlier steps in the fusion cascade. Here we investigate the function of Munc18a in reconstituted exocytic reactions mediated by neuronal and non-neuronal SNAREs...
August 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28826913/vorinostat-and-simvastatin-have-synergistic-effects-on-triple-negative-breast-cancer-cells-via-abrogating-rab7-prenylation
#12
Xinhui Kou, Yonghua Yang, Xiaoxiao Jiang, Huijuan Liu, Fanghui Sun, Xuan Wang, Longkai Liu, Hongrui Liu, Zhaohu Lin, Lan Jiang
Since the lack of targeted treatment, triple-negative breast cancer (TNBC) has poor outcomes. Histone deacetylase inhibitors (HDACi) blocking the activity of specific HDACs have emerged as cancer therapeutic agents. However, the therapeutic efficiency is still not satisfactory for patients with solid tumor. We thus performed screening for the synergistic agents of Vorinostat (SAHA). The resulting candidate Simvastatin was obtained. The efficacy and mechanism of combination have been studied in TNBC cells. The synergism of SAHA and Simvastatin was evaluated by IC50 of proliferation and combination index (CI)...
August 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28826368/impact-of-galectin-1-on-trophoblast-stem-cell-differentiation-and-invasion-in-in-vitro-implantation-model
#13
Minyue Tang, Jiali You, Wei Wang, Yongchao Lu, Xiaoling Hu, Chunyan Wang, Aixia Liu, Yimin Zhu
Trophoblast stem cells (TSCs) differentiate in an orderly manner, which plays an important role in the process of embryo implantation, placentation, and early pregnancy maintenance. At the maternal-fetal interface, the dialogue is crucial between trophoblast cells and endometrial epithelial cells. Previous studies suggested that galectin-1 (Gal-1) may play an important role in placental development. In this study, we used Ishikawa (IK) cells-TSC coculture model to simulate the maternal-fetal interface and induce the differentiation of TSCs by differentiation media...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28826347/osteogenic-potential-of-tauroursodeoxycholic-acid-tudca-as-an-alternative-to-rhbmp-2-in-a-mouse-spinal-fusion-model
#14
Byoung Ju Kim, Yoshie Arai, Eun-Mi Park, Sunghyun Park, Alvin Bacero Bello, In-Bo Han, Soo-Hong Lee
The non-union rate following lumbar spinal fusion is potentially as high as 48%. To support efficient bone regeneration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is commonly used as it is regarded as the most potent bone inducing molecule. However recently, there have been increasing concerns on the use of rhMBMP-2 such as serious complications including seroma and heterotopic ossification and the low quality of bone at the center of fusion mass. Thus, many studies were conducted to find and to develop a potential alternative to rhBMP-2...
August 21, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28823021/control-by-low-levels-of-calcium-of-mammalian-cell-membrane-electropermeabilization
#15
Ciobanu Florin, Golzio Muriel, Kovacs Eugenia, Teissié Justin
Electric pulses, when applied to a cell suspension, induce a reversible permeabilization of the plasma membrane. This permeabilized state is a long-lived process (minutes). The biophysical molecular mechanisms supporting the membrane reorganization associated to its permeabilization remain poorly understood. Modeling the transmembrane structures as toroidal lipidic pores cannot explain why they are long-lived and why their resealing is under the control of the ATP level. Our results describe the effect of the level of free Calcium ions...
August 20, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28822103/current-progress-in-innovative-engineered-antibodies
#16
REVIEW
William R Strohl
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year...
August 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28821767/identification-of-candidate-genes-for-devil-facial-tumour-disease-tumourigenesis
#17
Robyn L Taylor, Yiru Zhang, Jennifer P Schöning, Janine E Deakin
Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821638/fluorescent-probes-for-selective-protein-labeling-in-lysosomes-a-case-of-%C3%AE-galactosidase-a
#18
Cornelius Bohl, Adam Pomorski, Susanne Seemann, Anne-Marie Knospe, Chaonan Zheng, Artur Krężel, Arndt Rolfs, Jan Lukas
Fluorescence-based live-cell imaging (LCI) of lysosomal glycosidases is often hampered by unfavorable pH and redox conditions that reduce fluorescence output. Moreover, most lysosomal glycosidases are low-mass soluble proteins that do not allow for bulky fluorescent protein fusions. We selected α-galactosidase A (GALA) as a model lysosomal glycosidase involved in Anderson-Fabry disease (AFD) for the current LCI approach. Examination of the subcellular localization of AFD-causing mutants can reveal the mechanism underlying cellular trafficking deficits...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821194/primary-benign-and-malignant-thyroid-neoplasms-with-signet-ring-cells-cytologic-histologic-and-molecular-features
#19
Nada A Farhat, Ayse M Onenerk, Jeffrey F Krane, Dora Dias-Santagata, Peter M Sadow, William C Faquin
Objectives: Signet ring cells (SRCs) can be seen in a variety of thyroid tumors and can pose a diagnostic pitfall on cytology. This study describes the cytologic, histomorphologic, and molecular aspects of a cohort of primary thyroid tumors with SRCs. Methods: A search was performed of the Massachusetts General Hospital and Brigham and Women's Hospital (Boston, MA) pathology archives for the keywords thyroid, signet, and signet ring features between 2000 and 2014...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28819671/fullerenol-nanoparticles-suppress-rankl-induced-osteoclastogenesis-by-inhibiting-differentiation-and-maturation
#20
Huan Geng, Ya-Nan Chang, Xue Bai, Shuitao Liu, Qing Yuan, Weihong Gu, Juan Li, Kui Chen, Gengyan Xing, Gengmei Xing
Bone health requires regulation of homeostatic equilibrium between osteoblasts and osteoclasts. The over-activation of osteoclasts can disrupt bone metabolism, resulting in osteoporosis and other bone-loss diseases. Fullerenol, a polyhydroxy derivative of fullerene, exhibits excellent biocompatibility. Here we show that fullerenol nanoparticles exert two functions: inhibition of osteoclastic differentiation and blockage of pre-osteoclast fusion to restructure osteoclast maturation and function. Experimentally, the nanoparticles reduced pre-osteoclast migration and inhibited ruffled border formation to block their maturation...
August 18, 2017: Nanoscale
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