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https://www.readbyqxmd.com/read/29737200/human-peripheral-blood-mononuclear-cells-incubated-in-vasculogenic-conditioning-medium-dramatically-improve-ischemia-reperfusion-acute-kidney-injury-in-mice
#1
Takayasu Ohtake, Shuzo Kobayashi, Shimon Slavin, Yasuhiro Mochida, Kunihiro Ishioka, Hidekazu Moriya, Sumi Hidaka, Ryo Matsuura, Maki Sumida, Daisuke Katagiri, Eisei Noiri, Kayoko Okada, Hiroshi Mizuno, Rica Tanaka
Acute kidney injury (AKI) is a major clinical problem that still has no established treatment. We investigated the efficacy of cultured human peripheral blood mononuclear cells (PBMNCs) for AKI. Ischemia/reperfusion injury (IRI) was used to induce AKI in male nonobese diabetic (NOD/severe combined immunodeficiency) mice aged 7 to 8 wk. PBMNCs were isolated from healthy volunteers and were subjected to quality and quantity controlled (QQc) culture for 7 d in medium containing stem cell factor, thrombopoietin, Flt-3 ligand, vascular endothelial growth factor, and interleukin 6...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29732981/heterocyclization-of-thiophenes-derived-from-estrone-followed-by-cytotoxic-htrf-kinase-and-pim-1-kinase-evaluations
#2
Mahmoud Ali Abdelaziz Mahmoud, Rafat Milad Mohareb, Mashari Ahmed Alshereef
BACKGROUND: Among wide range of heterocyclic steroidal derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the steroid nucleus were known in the market. OBJECTIVE: Our main aim of this work was to synthesis a seies of heterocyclic compounds especially thiophene and thienopyridine derivatives containing the estrone nucleuous. The synthesized compounds possising antitumor and kinases inhibitions...
May 7, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29662864/expression-of-adhesion-molecules-on-cd34-cells-from-steady-state-bone-marrow-before-and-after-mobilization-and-their-association-with-the-yield-of-cd34-cells
#3
Karin Zattar Cecyn, Eliza Y S Kimura, Dulce Marta S M Lima, Miyoko Yamamoto, José Orlando Bordin, José Salvador R de Oliveira
Background: Cell adhesion molecules (CAMs) expressed on hematopoietic progenitor cells (HPCs), endothelial cells, and stromal cells play a pivotal role in the mobilization of CD34+ cells. Herein, we conducted a non-randomized peripheral blood stem cell (PBSC) mobilization study aimed to compare the potential differences in the expressions of several CAMs and chemokines on CD34+ cells obtained from bone marrow aspirate before and after HPC mobilization from patients with hematologic malignancies and healthy donors...
March 2018: Blood Research
https://www.readbyqxmd.com/read/29652619/circulating-cytokine-chemokine-concentrations-respond-to-ionizing-radiation-doses-but-not-radiation-dose-rates-granulocyte-colony-stimulating-factor-and-interleukin-18
#4
Juliann G Kiang, Joan T Smith, Sara R Hegge, Natalia I Ossetrova
Exposure to ionizing radiation is a crucial life-threatening factor in nuclear and radiological incidents. It is known that ionizing radiation affects cytokine/chemokine concentrations in the blood of B6D2F1 mice. It is not clear whether radiation dose rates would vary the physiological response. Therefore, in this study we utilized data from two experiments using B6D2F1 female mice exposed to six different dose rates ranging from low to high rates. In one experiment, mice received a total dose of 8 Gy (LD0/30 ) of 60 Co gamma radiation at four dose rates: 0...
April 13, 2018: Radiation Research
https://www.readbyqxmd.com/read/29516991/fast-recovery-of-platelet-production-in-nod-scid-mice-after-transplantation-with-ex-vivo-expansion-of-megakaryocyte-from-cord-blood-cd34-cells
#5
Hailian Wang, Wei Ge, Yong Zhuang, Jinqiu Fu, Dong Li, Xiuli Ju
Background: Cord blood transplantation (CBT) can be a life-saving procedure in the treatment of a broad variety of disorders, including hematologic, immune, and genetic diseases. However, delayed platelet recovery hinders the application of CBT. Purpose: The aim of this study was to determine the optimal combination of cytokines to amplify megakaryocyte (Mk). Methods: CB CD34+ cells were obtained by immunomagnetic isolation and amplified under four different cytokine combinations...
January 2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29421713/discovery-of-thinopyrimidine-triazole-conjugates-as-c-met-targeting-and-apoptosis-inducing-agents
#6
Linxiao Wang, Shan Xu, Xiaobo Liu, Xiuying Chen, Hehua Xiong, Shanshan Hou, Wensheng Zou, Qidong Tang, Pengwu Zheng, Wufu Zhu
Five series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing triazole (21-26, 27-34, 35-41, 42-47 and 48-54) were designed and synthesized. And all the target compounds were evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds (43, 49 and 52) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Moreover, SARs and docking studies indicated that thieno[3,2-d]pyrimidine bearing triazole moiety was privileged structure for the activity...
April 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29397825/-detection-of-novel-antigen-mlaa-34-gene-mutation-in-acute-monocytic-leukemia-and-its-correlation-with-efficacy
#7
Bo Lei, Wang-Gang Zhang, Yin-Xia Chen, Ai-Li He, Xing-Mei Cao, Wan-Hong Zhao, Jian-Li Wang, Jie Liu, Xiao-Rong Ma, Yun Yang, Peng-Yu Zhang, Jing Luo, Xin Meng
OBJECTIVE: To investigate the correlation of all exone mutation in MLAA-34 gene with chemotherapeutic efficacy for leukemia. METHODS: The expression level of MLAA-34 gene in 40 patients with AML-M5 and 5 healthy volunteers as control was detected by RT-PCR and its effect on chemotherapeutic efficacy were analyzed by RT-PCR; the effect of MLAA-34 gene mutation on overall survival (OS) and progression-free survival (PFS) of AML-M5 patients was analyzed by sequencing of all 12 exoues in MLAA-34 gene, the correlation between the mutation of prognostic genes important to leukemia and the mutation of MLAA-34 gene was explored...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29331754/synthesis-and-bioevaluation-and-doking-study-of-1h-pyrrolo-2-3-b-pyridine-derivatives-bearing-aromatic-hydrazone-moiety-as-c-met-inhibitors
#8
Wenhui Wang, Shan Xu, Yongli Duan, Xiaobo Liu, Xiaojing Li, Caolin Wang, Bingbing Zhao, Pengwu Zheng, Wufu Zhu
Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety (7a-r, 8a-i, 12a-b, 13a-c, 16a-d and 17a-e) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF-7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that targets compounds were selective for c-Met kinase. And the most promising compound 7c was further studied in terms of dose-dependent, time-dependent and cell apoptosis...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29317165/discovery-of-novel-2-substituted-4-phenoxypyridine-derivatives-as-potential-antitumor-agents
#9
Yongli Duan, Shan Xu, Hehua Xiong, Linxiao Wang, Bingbing Zhao, Ping Wang, Caolin Wang, Yiqing Peng, Shifan Cai, Rong Luo, Pengwu Zheng, Qidong Tang
A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC50 values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R1 group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R2  = 4-F) was benefited to the potency...
December 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29203143/synthesis-and-bioevaluation-study-of-novel-n-methylpicolinamide-and-thienopyrimidine-derivatives-as-selectivity-c-met-kinase-inhibitors
#10
Linxiao Wang, Shan Xu, Xiuying Chen, Xiaobo Liu, Yongli Duan, Dejia Kong, Dandan Zhao, Pengwu Zheng, Qidong Tang, Wufu Zhu
Four series of N-methylpicolinamide moiety and thienopyrimidine moiety bearing pyridazinone were designed and synthesized and evaluated for the IC50 values against three cancer cell lines (A549, HepG2 and MCF-7) and some selected compounds were further evaluated for the activity against c-Met, Flt-3, VEGFR-2, c-Kit and EGFR kinases. Three compounds (35, 39 and 43) showed more active than positive control Foretinib against A549, HepG2 and MCF-7 cell lines. The most promising compound 43 showed superior activity against A549, HepG2 and MCF-7, with the IC50 values of 0...
January 1, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29197731/synthesis-and-antiproliferative-activity-of-pyrrolo-2-3-b-pyridine-derivatives-bearing-the-1-8-naphthyridin-2-one-moiety
#11
Qidong Tang, Yongli Duan, Linxiao Wang, Min Wang, Yiqiang Ouyang, Caolin Wang, Han Mei, Sheng Tang, Yinhua Xiong, Pengwu Zheng, Ping Gong, Wufu Zhu
A series of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety were synthesized, and evaluated for their antiproliferative activity against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine kinases (c-Met, Flt-3, PDGFR-β, VEGFR-2, EGFR, and c-Kit) inhibitory activities in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 32 showing Flt-3/c-Met IC50 value of 1.16/1.92 nM. Structure-activity relationship studies indicated that the hydrogen atom served as R1 group was benefited to the potency, and mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring (such as R3  = 4-F) showed a higher preference for antiproliferative activity...
January 1, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29107421/discovery-of-novel-pyrrolo-pyridine-pyrimidine-derivatives-bearing-pyridazinone-moiety-as-c-met-kinase-inhibitors
#12
Lin Xiao Wang, Xiaobo Liu, Shan Xu, Qidong Tang, Yongli Duan, Zhen Xiao, Jia Zhi, Liwen Jiang, Pengwu Zheng, Wufu Zhu
In continue to our previous research, eight series of pyrrolo[2,3-b]pyridine and pyrrolo[2,3-d]pyrimidine derivatives bearing pyridazinone moiety were designed, synthesized, and the in vitro antitumor activity was evaluated against four cancer cell lines (A549, HepG2, MCF-7 and PC-3). Some selected compounds (22f, 22g, 26c and 26e) were evaluated for the activity against c-Met kinase, and according to the results of kinase inhibitory activity, the compound 22g was further evaluated for other four tyrosine kinases (Flt-3, VEGFR-2, c-Kit and EGFR) to test the enzyme-based selectivity...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29042609/structural-analysis-of-pim1-kinase-complexes-with-atp-competitive-inhibitors
#13
Jozefina Bogusz, Karol Zrubek, Krzysztof P Rembacz, Przemyslaw Grudnik, Przemyslaw Golik, Malgorzata Romanowska, Benedykt Wladyka, Grzegorz Dubin
PIM1 is an oncogenic kinase overexpressed in a number of cancers where it correlates with poor prognosis. Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934227/hemorrhage-enhances-cytokine-complement-component-3-and-caspase-3-and-regulates-micrornas-associated-with-intestinal-damage-after-whole-body-gamma-irradiation-in-combined-injury
#14
Juliann G Kiang, Joan T Smith, Marsha N Anderson, Thomas B Elliott, Paridhi Gupta, Nagaraja S Balakathiresan, Radha K Maheshwari, Barbara Knollmann-Ritschel
Hemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone...
2017: PloS One
https://www.readbyqxmd.com/read/28927801/design-synthesis-and-antitumor-activity-of-novel-sorafenib-derivatives-bearing-pyrazole-scaffold
#15
Min Wang, Shan Xu, Huajun Lei, Caolin Wang, Zhen Xiao, Shuang Jia, Jia Zhi, Pengwu Zheng, Wufu Zhu
Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC50 value of compounds 8b on VEGFR-2 kinase was 0...
September 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28893953/fate-decision-between-group-3-innate-lymphoid-and-conventional-nk-cell-lineages-by-notch-signaling-in-human-circulating-hematopoietic-progenitors
#16
Seishi Kyoizumi, Yoshiko Kubo, Junko Kajimura, Kengo Yoshida, Tomonori Hayashi, Kei Nakachi, Malcolm A Moore, Marcel R M van den Brink, Yoichiro Kusunoki
The role of Notch signaling in human innate lymphoid cell (ILC) differentiation is unclear, although IL-7 and IL-15 promote differentiation of natural cytotoxicity receptor (NCR) NKp44+ group 3 ILCs (NCR+ ILC3s) and conventional NK (cNK) cells from CD34+ hematopoietic progenitor cells (HPCs) ex vivo. In this study, we analyzed the functions of Notch in the differentiation of NCR+ ILC3s and cNK cells from human HPC subpopulations circulating in peripheral blood by limiting dilution and clonal assays using high-throughput flow cytometry...
October 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28799432/targeted-therapies-in-acute-myeloid-leukemia-a-focus-on-flt-3-inhibitors-and-abt199
#17
REVIEW
Kiran Naqvi, Marina Konopleva, Farhad Ravandi
Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target...
October 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28545284/-expression-profiles-and-clinical-implication-of-plasma-chemokines-in-patients-with-stanford-type-a-aortic-dissection
#18
F D Fan, Z J Xu, Q Zhou, D J Wang
Objective: To explore the plasma chemokines expressions and related clinical implication in patients with Stanford type A aortic dissection (AD). Methods: We retrospectively analyzed the data of 65 patients with Stanford type A aortic dissection, hypertensive patients and 11 healthy subjects admitted in our department from October 2013 to December 2014, they were divided into four groups: NH-CON group (11 healthy subjects), H-AD group (29 AD patients with hypertension), NH-AD group (21 AD patients without hypertension), and H-CON group (14 hypertension patients)...
April 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28362701/acute-myeloid-leukemia-aml-upregulation-of-baalc-mn1-mllt11-evi1-gene-cluster-relate-with-poor-overall-survival-and-a-possible-linkage-with-coexpression-of-myc-bcl2-proteins
#19
Ariz Akhter, Fahad Farooq, Ghaleb Elyamany, Muhammad K Mughal, Fariborz Rashid-Kolvear, Meer-Taher Shabani-Rad, Lesley Street, Adnan Mansoor
BACKGROUND: Molecular heterogeneity accounts for the variable and often poor prognosis in acute myeloid leukemia (AML). The current risk stratification strategy in clinical practice is limited to karyotyping and limited molecular studies screening for genetic mutations such as FLT-3 and NPM1. There is opportunity to identify further molecular prognostic markers, which may also lay the groundwork for the development of novel targeted therapies. Complex molecular technologies require transition into widely available laboratory platforms, for better integration into routine clinical practice...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28102569/human-%C3%AE-defensin-3-increases-the-tlr9-dependent-response-to-bacterial-dna
#20
Sarah L McGlasson, Fiona Semple, Heather MacPherson, Mohini Gray, Donald J Davidson, Julia R Dorin
Human β-defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self-DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt-3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E...
April 2017: European Journal of Immunology
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