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C-kit AND SCF

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https://www.readbyqxmd.com/read/27890784/identifying-residues-that-determine-scf-molecular-level-interactions-through-a-combination-of-experimental-and-in-silico-analyses
#1
Eitan Rabinovich, Michael Heyne, Anna Bakhman, Mickey Kosloff, Julia M Shifman, Niv Papo
The stem cell factor (SCF)/c-Kit receptor tyrosine kinase complex - with its significant roles in hematopoiesis and angiogenesis - is an attractive target for rational drug design. There is thus a need to map, in detail, the SCF/c-Kit interaction sites and the mechanisms that modulate this interaction. While most residues in the direct SCF/c-Kit binding interface can be identified from the existing crystal structure of the complex, other residues that affect binding through protein unfolding, intermolecular interactions, or allosteric or long-distance electrostatic effects cannot be directly inferred...
November 24, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27872880/data-on-quantification-of-signaling-pathways-activated-by-kit-and-pdgfra-mutants
#2
Christelle Bahlawane, Martine Schmitz, Elisabeth Letellier, Karthik Arumugam, Nathalie Nicot, Petr V Nazarov, Serge Haan
The present data are related to the article entitled "Insights into ligand stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane, M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016) [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were compared. Expression of mutant proteins was induced by doxycycline in an isogenic background (Hek293 cells). Kit was identified by FACS at the cell surface and found to be quickly degraded or internalized upon SCF stimulation for both Kit Wild type and Kit mutant counterparts...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27825164/effect-of-neutrophils-on-gallbladder-interstitial-cajal-like-cells-in-guinea-pig-model-of-acute-cholecystitis
#3
Zhen-Peng Huang, Hu Qiu, Yan Yang, Bao-Ping Yu
BACKGROUND: Acute cholecystitis is a common condition in gallbladder motility disorder. Interstitial Cajal-like cells (ICLCs) in the gallbladder are known as one of the players in the complex motility mechanisms affecting gallbladder motility. AIM: This study explored morphological symptoms and molecular mechanisms underlying gallbladder ICLC changes induced by acute cholecystitis. MATERIALS AND METHODS: Fifteen adult guinea pigs were randomly divided into 3 groups: sham-operated group (healthy controls) and 2 experimental groups wherein these guinea pigs were subjected to common bile duct ligation to induce acute cholecystitis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27798921/low-mast-cell-density-predicts-poor-prognosis-in-oral-squamous-cell-carcinoma-and-reduces-survival-in-head-and-neck-squamous-cell-carcinoma
#4
Cecilie Gjøvaag Attramadal, Sheeba Kumar, Jian Gao, Morten Ebbe Boysen, Trond Sundby Halstensen, Magne Bryne
BACKGROUND: The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCs) may reflect biologically important cancer features and host responses, and thus be related to disease progression. The TME density of mast cells (MCs), macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells were quantified at the invasive front and analyzed regarding their relation to disease recurrence in patients with small T1/2N0M0 OSCCs...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27782131/in-vivo-correction-of-anaemia-in-%C3%AE-thalassemic-mice-by-%C3%AE-pna-mediated-gene-editing-with-nanoparticle-delivery
#5
Raman Bahal, Nicole Ali McNeer, Elias Quijano, Yanfeng Liu, Parker Sulkowski, Audrey Turchick, Yi-Chien Lu, Dinesh C Bhunia, Arunava Manna, Dale L Greiner, Michael A Brehm, Christopher J Cheng, Francesc López-Giráldez, Adele Ricciardi, Jagadish Beloor, Diane S Krause, Priti Kumar, Patrick G Gallagher, Demetrios T Braddock, W Mark Saltzman, Danith H Ly, Peter M Glazer
The blood disorder, β-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the γ position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human β-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing γPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal of splenomegaly and up to 7% β-globin gene correction in HSCs, with extremely low off-target effects...
October 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27707610/aberrant-expressions-of-stem-cell-factor-c-kit-in-rat-testis-with-varicocele
#6
Qin Qin, Jianrong Liu, Yuehong Ma, Yimin Wang, Fang Zhang, Songdan Gao, Lina Dong
BACKGROUND/PURPOSE: Varicocele (VC) is considered by the World Health Organization as the main cause of male infertility. Studies have shown that VC can affect spermatogenesis and then result in male infertility. But the exact mechanism by which VC affects spermatogenesis is still unclear. Stem cell factor (SCF) and c-KIT receptor are crucial molecules during spermatogenesis in testis. This study aims to investigate whether SCF/c-KIT signaling is involved in the pathophysiology of VC on spermatogenesis...
October 2, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/27606906/positive-oct-3-4-and-d2-40-immunohistochemical-expression-in-germ-cells-and-suspected-histology-pattern-of-intratubular-germ-cell-neoplasia-in-boys-with-cryptorchidism-vanish-after-the-age-of-2-years
#7
Jorgen Thorup, Erik Clasen-Linde, Dina Cortes
Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy...
September 8, 2016: European Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/27539014/enhanced-hematopoietic-stem-cell-self-renewal-promoting-ability-of-clonal-primary-mesenchymal-stromal-stem-cells-versus-their-osteogenic-progeny
#8
Qiling He, Claude Scott Swindle, Chao Wan, Robert J Flynn, Robert A Oster, Dongquan Chen, Fengjie Zhang, Yinglan Shu, Christopher A Klug
Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC subpopulation that was uniformly Nestin(+) Lepr (+) Sca-1(+) CD146(+) and could be stably propagated with high colony-forming unit fibroblast re-cloning efficiency...
August 19, 2016: Stem Cells
https://www.readbyqxmd.com/read/27478893/total-glucosides-of-paeony-promote-intestinal-motility-in-slow-transit-constipation-rats-through-amelioration-of-interstitial-cells-of-cajal
#9
Feiye Zhu, Shan Xu, Yongsheng Zhang, Fangming Chen, Jinjun Ji, Guanqun Xie
OBJECTIVES: Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms. STUDY DESIGN: A prospective experimental animal study. METHODS: The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated...
2016: PloS One
https://www.readbyqxmd.com/read/27451973/a-novel-slug-containing-negative-feedback-loop-regulates-scf-c-kit-mediated-hematopoietic-stem-cell-self-renewal
#10
Z Zhang, P Zhu, Y Zhou, Y Sheng, Y Hong, D Xiang, Z Qian, J Mosenson, W-S Wu
The SCF/c-Kit pathway has crucial roles in controlling hematopoietic stem cell (HSC) renewal. However, little is known about the intracellular regulation of the SCF/c-Kit pathway in HSCs. We report here that Slug, a zinc-finger transcription repressor, functions as a direct transcriptional repressor of c-Kit in HSCs. Conversely, SCF/c-Kit signaling positively regulates Slug through downstream c-Myc and FoxM1 transcription factors. Intriguingly, c-Kit expression is induced by SCF/c-Kit signaling in Slug-deficient HSCs...
July 25, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27451100/molecular-signaling-pathways-controlling-vascular-tube-morphogenesis-and-pericyte-induced-tube-maturation-in-3d-extracellular-matrices
#11
S L K Bowers, P R Norden, G E Davis
During capillary network formation, ECs establish interconnecting tubes with defined lumens that reside within vascular guidance tunnels (physical spaces generated during EC tubulogenesis). Pericytes are recruited to EC tubes within these tunnels and capillary basement membrane deposition occurs to facilitate tube maturation. Here, we discuss molecular mechanisms controlling EC tubulogenesis demonstrating the involvement of integrins, MT1-MMP, extracellular matrix, Cdc42, Rac1, Rac2, k-Ras, Rap1b, and key downstream effectors including Pak2, Pak4, IQGAP1, MRCKβ, and Rasip1...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27340921/impact-of-the-scf-signaling-pathway-on-leukemia-stem-cell-mediated-atl-initiation-and-progression-in-an-hbz-transgenic-mouse-model
#12
Wakako Kuribayashi, Kazuya Takizawa, Kenji Sugata, Madoka Kuramitsu, Haruka Momose, Eita Sasaki, Yuki Hiradate, Keiko Furuhata, Yoshihisa Asada, Atsushi Iwama, Masao Matsuoka, Takuo Mizukami, Isao Hamaguchi
Adult T-cell leukemia (ATL) is a malignant disease caused by human T-lymphotropic virus type 1. In aggressive ATL, the response to chemotherapy is extremely poor. We hypothesized that this poor response is due to the existence of chemotherapy-resistant cells, such as leukemic stem cells. Previously, we successfully identified an ATL stem cell (ATLSC) candidate as the c-kit+/CD38-/CD71- cells in an ATL mouse model using Tax transgenic mice. Here, with a new ATL mouse model using HBZ-transgenic mice, we further discovered that the functional ATLSC candidate, which commonly expresses c-kit, is drug-resistant and has the ability to initiate tumors and reconstitute lymphomatous cells...
June 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27340351/long-pulse-gastric-electrical-stimulation-protects-interstitial-cells-of-cajal-in-diabetic-rats-via-igf-1-signaling-pathway
#13
Hai Li, Yan Chen, Shi Liu, Xiao-Hua Hou
AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5...
June 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27330532/mast-cell-targeted-strategies-in-cancer-therapy
#14
REVIEW
Michele Ammendola, Rosario Sacco, Giuseppe Sammarco, Maria Luposella, Rosa Patruno, Cosmo Damiano Gadaleta, Giovambattista De Sarro, Girolamo Ranieri
Mast cells (MCs) are cells that originate in the bone marrow from pluripotent CD34+ hematopoietic stem cells. Precursors of MCs migrate through the circulation to their target tissues, completing their maturation process into granulated cells under the influence of several microenvironment growth factors. The most important of these factors is the ligand for the c-Kit receptor (c-Kit-R) namely stem cell factor (SCF), secreted mainly by fibroblasts and endothelial cells (ECs). SCF also regulates development, survival and de novo proliferation of MCs...
March 2016: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/27323927/mir-137-affects-melanin-synthesis-in-mouse-melanocyte-by-repressing-the-expression-of-c-kit-and-tyrp2-in-scf-c-kit-signaling-pathway
#15
Shan Jiang, Xiuju Yu, Changsheng Dong
Previously, we created miR-137 overexpressing transgenic mice that produced lighten color phenotypes including gray mice phenotype. However, the miR-137 functional role in coat color regulation is still not well understood. In this study, the quantity of melanin granule and the relative expression of TYRP2 in gray miR-137 overexpression transgenic mouse skin were significantly lower than that in C57BL/6J black mouse skin. The mRNA and protein expression level of c-Kit and c-Kit downstream gene Tyrp2 in miR-137 expression plasmid-transfected melanocytes were significantly down-regulated comparing with that of the control melanocytes...
June 21, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27292026/a-positive-tgf-%C3%AE-c-kit-feedback-loop-drives-tumor-progression-in-advanced-primary-liver-cancer
#16
Andres Rojas, Pingyu Zhang, Ying Wang, Wai Chin Foo, Nina M Muñoz, Lianchun Xiao, Jing Wang, Gregory J Gores, Mien-Chie Hung, Boris Blechacz
UNLABELLED: Hepatocellular carcinoma (HCC) is globally the second most common cause of cancer mortality. The majority of HCC patients are diagnosed at advanced stage disease for which no curative treatments exist. TGF-β has been identified as a potential therapeutic target. However, the molecular mechanisms mediating its functional switch from a tumor suppressor to tumor promoter in HCC and its interactions with other signaling pathways are poorly understood. Here, we demonstrate an aberrant molecular network between the TGF-β and c-KIT pathway that mediates the functional switch of TGF-β to a driver of tumor progression in HCC...
June 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27279472/stem-cell-factor-promotes-in-vitro-ovarian-follicle-development-in-the-domestic-cat-by-upregulating-c-kit-mrna-expression-and-stimulating-the-phosphatidylinositol-3-kinase-akt-pathway
#17
Paweena Thuwanut, Pierre Comizzoli, David E Wildt, Carol L Keefer, Nucharin Songsasen
In the present study we examined the effects of stem cell factor (SCF; 50 vs 100 ng mL-1) alone or in combination with epidermal growth factor (EGF; 100 ng mL-1) on: (1) the in vitro viability and growth of cat follicles within ovarian cortices; (2) phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) phosphorylation; and (3) c-kit and FSH receptor (FSHr) mRNA expression. At 100 ng mL-1, SCF increased (P ≤ 0.05) the percentage and size of secondary follicles after 14 days of in vitro culture and sustained AKT phosphorylation after 3 days incubation...
June 9, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27245949/scf-c-kit-transactivates-cxcr4-serine-339-phosphorylation-through-g-protein-coupled-receptor-kinase-6-and-regulates-cardiac-stem-cell-migration
#18
Ke Zuo, Dong Kuang, Ying Wang, Yanli Xia, Weilin Tong, Xiaoyan Wang, Yaobin Chen, Yaqi Duan, Guoping Wang
C-kit positive cardiac stem cells (CSCs) have been shown to contribute to myocardial regeneration after infarction. Previously, we have shown that the c-kit ligand stem cell factor (SCF) can induce CSC migration into the infarcted area during myocardial infarction (MI). However, the precise mechanism involved is not fully understood. In this study, we found that CSCs also express C-X-C chemokine receptor type 4 (CXCR4), which is a typical member of the seven transmembrane-spanning G protein-coupled receptor (GPCR)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27234501/role-of-stem-cell-factor-in-the-placental-niche
#19
Elahe Khodadi, Saeid Shahrabi, Mohammad Shahjahani, Saeed Azandeh, Najmaldin Saki
Stem cell factor (SCF) is a cytokine found in hematopoietic stem cells (HSCs) and causes proliferation and differentiation of cells by binding to its receptor (c-kit). It is produced in the yolk sac, fetal liver and bone marrow during the development of the fetus and, together with its signaling pathway, plays an important role in the development of these cells. The placenta, an important hematopoiesis site before the entry of cells into the liver, is rich in HSCs, with definitive hematopoiesis in a variety of HSC types and embryonic stem cells...
May 28, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27178146/cancer-cell-motility-is-affected-through-3d-cell-culturing-and-scf-c-kit-pathway-but-not-by-x-irradiation
#20
Fabian Eberle, Miriam F Saulich, Florian H Leinberger, Werner Seeger, Rita Engenhart-Cabillic, Ekkehard Dikomey, Jörg Hänze, Katja Hattar, Florentine S B Subtil
BACKGROUND AND PURPOSE: Success of radiotherapy is often limited by therapy resistance and metastasis resulting from cancer cell motility. It was tested in vitro whether this cancer cell motility is affected by growth condition, active SCF/c-Kit pathway or X-irradiation. MATERIALS AND METHODS: Cell motility was measured with BioCoat™ Matrigel™ invasion chamber using four different cancer cell lines (NSCLC: H23, H520, H226 and PrCa: DU145). Cells were grown in 2D or 3D, SCF was knocked down by siRNA and cells were irradiated with 2 or 6Gy...
June 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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