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https://www.readbyqxmd.com/read/29791894/highly-tumorigenic-diffuse-large-b-cell-lymphoma-cells-are-produced-by-coculture-with-stromal-cells
#1
Zhiguang Lin, Bobin Chen, Ting Wu, Xiaoping Xu
BACKGROUND/AIMS: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. METHODS: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot...
May 23, 2018: Acta Haematologica
https://www.readbyqxmd.com/read/29783777/preferential-inhibition-of-wnt-%C3%AE-catenin-signaling-by-novel-benzimidazole-compounds-in-triple-negative-breast-cancer
#2
Abhishek Gangrade, Vibha Pathak, Corinne E Augelli-Szafran, Han-Xun Wei, Patsy Oliver, Mark Suto, Donald J Buchsbaum
Wnt/β-catenin signaling is upregulated in triple-negative breast cancer (TNBC) compared to other breast cancer subtypes and normal tissues. Current Wnt/β-catenin inhibitors, such as niclosamide, target the pathway nonspecifically and exhibit poor pharmacokinetics/pharmacodynamics in vivo. Niclosamide targets other pathways, including mTOR, STAT3 and Notch. Novel benzimidazoles have been developed to inhibit Wnt/β-catenin signaling with greater specificity. The compounds SRI33576 and SRI35889 were discovered to produce more cytotoxicity in TNBC cell lines than in noncancerous cells...
May 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#3
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29771334/%C3%AE-catenin-activation-in-hair-follicle-dermal-stem-cells-induces-ectopic-hair-outgrowth-and-skin-fibrosis
#4
Yixin Tao, Qingchun Yang, Lei Wang, Jie Zhang, Xuming Zhu, Qianqian Sun, Yunbin Han, Qian Luo, Yushu Wang, Xizhi Guo, Ji Wu, Baojie Li, Xiao Yang, Lin He, Gang Ma
Hair follicle dermal sheath (DS) harbors hair follicle dermal stem cells (hfDSCs), which can be recruited to replenish DS and dermal papilla (DP). Cultured DS cells can differentiate into various cell lineages in vitro. However, it is unclear how its plasticity is modulated in vivo. Wnt/β-catenin signaling plays an important role in maintaining stem cells of various lineages and is required for HF development and regeneration. Here we report that activation of β-catenin in DS generates ectopic HF outgrowth (EF) by reprogramming HF epidermal cells and DS cells themselves, and endows DS cells with hair inducing ability...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29768476/treatment-with-specific-soluble-factors-promotes-the-functional-maturation-of-transcription-factor-mediated-pancreatic-transdifferentiated-cells
#5
Hiroaki Motoyama, Akira Kobayashi, Takahide Yokoyama, Akira Shimizu, Hiroshi Sakai, Tsuyoshi Notake, Kentaro Fukushima, Shin-Ichi Miyagawa
Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells...
2018: PloS One
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#6
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29758550/microrna-449a-inhibition-protects-h9c2-cells-against-hypoxia-reoxygenation-induced-injury-by-targeting-the-notch-1-signaling-pathway
#7
Jing Cheng, Qianfu Wu, Rong Lv, Li Huang, Banglong Xu, Xianbao Wang, Aihua Chen, Fei He
BACKGROUND/AIMS: The present study aimed to detect the expression of miR-449a and investigate the effect of miR-449a on cell injury in cardiomyocytes subjected to hypoxia/ reoxygenation (H/R) and its underlying mechanisms. METHODS: The expression of miR-449a was determined using reverse transcription-polymerase chain reaction in both neonatal rat ventricular myocytes and H9C2 cells. For gain-of-function and loss-of-function studies, H9C2 cells were transfected with either miR-449a mimics or miR-449a inhibitor...
May 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29754932/mild-hypothermia-inhibits-the-notch-3-and-notch-4-activation-and-seizure-after-stroke-in-the-rat-model
#8
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Ischemic brain injury is an important cause for seizure. Mild hypothermia of the brain or the whole body is an effective way to remit the post-stroke seizure. Our previous study revealed an implication of Notch 1 and 2 in the post-stroke seizure. This study further investigated the involvement of Notch 3 and 4 in post-stroke seizure and the effect of mild hypothermia on these two factors. A global cerebral ischemia (GCI) model was conducted in Sprague Dawley rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29750292/microrna%C3%A2-381-hes1-is-a-potential-therapeutic-target-for-spinal-cord-injury
#9
Wendong Ruan, Guangzhi Ning, Shiqing Feng, Shijie Gao, Yan Hao
The aim of the present study was to investigate whether microRNA‑381 is a potential therapeutic target for spinal cord injury (SCI) and its possible mechanism. Reverse transcription quantitative polymerase chain reaction (qPCR) for mRNA expression was used to analyze the changes of microRNA-381 expression. Cell viability and cell apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Caspase‑3 activity was measured using caspase‑3 activity kit, and western blot analysis was used to measure the protein expression of neurogenic locus notch homolog protein 1 (Notch1), notch 1 intracellular domain (NICD) and transcription factor HES-1 (Hes1)...
May 8, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29749927/the-transcriptomic-and-epigenetic-map-of-vascular-quiescence-in-the-continuous-lung-endothelium
#10
Katharina Schlereth, Dieter Weichenhan, Tobias Bauer, Tina Heumann, Evangelia Giannakouri, Daniel Lipka, Samira Jaeger, Matthias Schlesner, Patrick Aloy, Roland Eils, Christoph Plass, Hellmut G Augustin
Maintenance of a quiescent and organotypically-differentiated layer of blood vessel-lining endothelial cells (EC) is vital for human health. Yet, the molecular mechanisms of vascular quiescence remain largely elusive. Here we identify the genome-wide transcriptomic program controlling the acquisition of quiescence by comparing lung EC of infant and adult mice, revealing a prominent regulation of TGFß family members. These transcriptomic changes are distinctly accompanied by epigenetic modifications, measured at single CpG resolution...
May 11, 2018: ELife
https://www.readbyqxmd.com/read/29743551/a-novel-method-for-expansion-and-differentiation-of-mouse-tracheal-epithelial-cells-in-culture
#11
Evelien Eenjes, Tinne C J Mertens, Marjon J Buscop-van Kempen, Yolanda van Wijck, Christian Taube, Robbert J Rottier, Pieter S Hiemstra
Air-liquid interface (ALI) cultures of mouse tracheal epithelial cells (MTEC) are a well-established model to study airway epithelial cells, but current methods require large numbers of animals which is unwanted in view of the 3R principle and introduces variation. Moreover, stringent breeding schemes are frequently needed to generate sufficient numbers of genetically modified animals. Current protocols do not incorporate expansion of MTEC, and therefore we developed a protocol to expand MTEC while maintaining their differentiation capacity...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29737480/notch-signaling-regulates-microglial-activation-and-inflammatory-reactions-in-a-rat-model-of-temporal-lobe-epilepsy
#12
Lei Wu, Yushuang Li, Minhua Yu, Fei Yang, Mengqi Tu, Haibo Xu
The inflammatory response mediated by microglia in the central nervous system is closely related to epilepsy. Notch signaling plays an important role in the microglial activation during hypoxia. This study aimed to investigate whether Notch signaling is involved in microglial activation and subsequent inflammation-related neuronal injury during the process of epileptogenesis in a rat model of temporal lobe epilepsy. By using western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence labeling, we found that the expression of Notch signaling increased after status epilepticus and that a γ-secretase inhibitor could significantly inhibit the upregulation of Notch signaling, the activation of microglia, and the release of proinflammatory cytokines...
May 8, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29735551/novel-richter-s-syndrome-xenograft-models-to-study-genetic-architecture-biology-and-therapy-responses
#13
Tiziana Vaisitti, Esteban Braggio, John N Allan, Francesca Arruga, Sara Serra, Alberto Zamò, Wayne Tam, Amy Chadburn, Richard R Furman, Silvia Deaglio
Richter's syndrome (RS) represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemo-immunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft models of RS, RS9737 and RS1316. RS xenografts were genetically, morphologically and phenotypically stable and similar to the corresponding primary tumor...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29726088/a-novel-2-phenylamino-quinazoline-based-compound-expands-the-neural-stem-cell-pool-and-promotes-the-hippocampal-neurogenesis-and-the-cognitive-ability-of-adult-mice
#14
Lu Hui, Cheng Gang, Hong Feng, Zhang Lei, Hu Youhong, Feng Linyin
The adult neurogenesis occurs throughout the life of the mammalian hippocampus and is found to be essential for learning and memory. Identifying new ways to manipulate the number of neural stem cells (NSCs) and enhance endogenous neurogenesis in adult is very important. Here we found that a novel compound, N2-(4-isopropylphenyl)-5-(3-methoxyphenoxy)quinazoline-2,4-diamine (code-named Yhhu-3792), enhanced the self-renewal capability of NSCs in vitro and in vivo. In vitro, Yhhu-3792 increased the ratio of BrdU + /DAPI+ embryonic NSCs and accelerated the growth of neurospheres significantly...
May 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29721169/differentiation-inducing-therapeutic-effect-of-notch-inhibition-in-reversing-malignant-transformation-of-liver-normal-stem-cells-via-met
#15
Hao Luo, Wei-Hui Liu, Hong-Yin Liang, Hong-Tao Yan, Ning Lin, Dong-Yu Li, Tao Wang, Li-Jun Tang
Background: Liver cancer stem cells (LCSCs) are the key factors for cancer metastasis, recurrent, and drug resistance. LCSCs are originated from either hepatocytes dedifferentiation or differentiation arresting of liver normal stem cells (LNSCs). Differentiation-inducing therapy is a novel strategy in solid tumors. Furthermore, Notch signaling pathway has been proved to play important role in the process of hepatocytes differentiation. In previous study, a malignant transformation cellular model of LNSCs has been built up, and in this study we are trying to illustrate whether inhibition of Notch can reverse this malignant tendency and drive these malignant cells back to differentiate into mature hepatocytes...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720422/gremlin-activates-the-notch-pathway-linked-to-renal-inflammation
#16
Carolina Lavoz, Jonay Poveda, Laura Márquez-Expósito, Sandra Rayego-Mateos, Raul R Rodrigues-Diez, Alberto Ortiz, Jesús Egido, Sergio Mezzano, Marta Ruiz-Ortega
Preclinical studies suggest that Gremlin participates in renal damage and could be a potential therapeutic target for human chronic kidney diseases. Inflammation is a common characteristic of progressive renal disease, and therefore novel anti-inflammatory therapeutic targets should be investigated. The Notch signaling pathway is involved in kidney development and is activated in human chronic kidney disease, but whether Gremlin regulates the Notch pathway has not been investigated. In cultured tubular cells, Gremlin up-regulated gene expression of several Notch pathway components, increased the production of the canonical ligand Jagged-1 and caused the nuclear translocation of active Notch-1 (N1ICD)...
May 2, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29719609/characterization-of-a-new-b-all-cell-line-with-constitutional-defect-of-the-notch-signaling-pathway
#17
Paul Takam Kamga, Giada Dal Collo, Giulio Bassi, Martina Midolo, Massimo Delledonne, Marco Chilosi, Massimiliano Bonifacio, Mauro Krampera
Notch signaling contribution to B-cell acute lymphoblastic leukemia (B-ALL) development is still under investigation. The serendipitous onset of B-ALL in a patient affected by the germinal Notch mutation-dependent Alagille syndrome allowed us to establish a B-ALL cell line (VR-ALL) bearing a genetic loss of function in components of Notch signaling. VR-ALL is a common-type B-ALL cell line, grows in conventional culture medium supplemented with 10% serum, and gives rise, once injected into immunodeficient NOG mice, to a mouse xenograft model of B-ALL...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719602/leptin-notch-axis-impairs-5-fluorouracil-effects-on-pancreatic-cancer
#18
Adriana Harbuzariu, Ruben Rene Gonzalez-Perez
5-FU chemotherapy is a current strategy to treat pancreatic cancer (PC), but unfortunately chemoresistance is eventually developed in most patients. Obesity is a risk factor for PC that could affect 5-FU effectiveness through the adipokine leptin, which is a known proliferation, survival factor and Notch inducer. We investigated whether leptin signaling affects 5-FU cytotoxicity on PC. To this end, tumorspheres developed from BxPC-3 and MiaPaCa-2 PC cells were treated with 5-FU, leptin, inhibitors for Notch (DAPT) and leptin signaling (IONP-LPrA2) and ATP-binding cassette of proteins (Probenecid)...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29702280/crosstalk-between-toll-like-receptor-3-and-notch-signaling-contributes-to-cd14-monocytes-activity-in-enterovirus-71-infected-hand-foot-and-mouth-disease
#19
Jie Hao, Peiling Li, Yunjiao Tian, Yanhua Wang, Suqing Li, Lina Wang, Shujun Li
Interaction between Toll-like receptor (TLR) and Notch signaling contributes to inflammatory response in nephropathy and fungicidal infection, however, the role of this crosstalk remains not fully elucidated in enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). The aim of this study was to investigate the crosstalk between TLR and Notch in inflammatory regulation in EV71 infection. Thirty-seven EV-71-indcued HFMD (16 mild and 21 severe cases) and eleven normal control (NC) were enrolled. CD14+ monocytes were purified, and were stimulated with either TLR3/4 agonists [poly(I: C) or LPS] or Notch signaling inhibitor...
April 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29702197/mutations-in-the-estrogen-receptor-alpha-hormone-binding-domain-promote-stem-cell-phenotype-through-notch-activation-in-breast-cancer-cell-lines
#20
L Gelsomino, S Panza, C Giordano, I Barone, G Gu, E Spina, S Catalano, S Fuqua, S Andò
The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behaviour of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44+ /CD24- ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities...
April 24, 2018: Cancer Letters
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