BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells

Nurhayati, Retno Wahyu; Ojima, Yoshihiro; Taya, Masahito

doi:10.1007/s13577-014-0102-2

Cited by 10 publications

(7 citation statements)

References 33 publications

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“…In a KHT sarcoma rodent tumour model, BMS-777607 impaired metastasis [225], led to the regression of intracranial glioma tumour growth and reduced AXL-related tumour angiogenesis [43]. In addition, BMS-777607 is a potent polyploidy inducer that promotes the megakaryocytic differentiation of CHRF-288-11 cells [227]. This compound is now undergoing phase I/II clinical trials in patients with advanced or metastatic tumours (NCT01721148 and NCT00605618).…”

Section: Axl-targeted Therapiesmentioning

confidence: 99%

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

2019

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Molecular targeted therapy for cancer has been a research hotspot for decades. AXL is a member of the TAM family with the high-affinity ligand growth arrest-specific protein 6 (GAS6). The Gas6/AXL signalling pathway is associated with tumour cell growth, metastasis, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation and stem cell maintenance. Different therapeutic agents targeting AXL have been developed, typically including small molecule inhibitors, monoclonal antibodies (mAbs), nucleotide aptamers, soluble receptors, and several natural compounds. In this review, we first provide a comprehensive discussion of the structure, function, regulation, and signalling pathways of AXL. Then, we highlight recent strategies for targeting AXL in the treatment of cancer.AXL-targeted drugs, either as single agents or in combination with conventional chemotherapy or other small molecule inhibitors, are likely to improve the survival of many patients. However, future investigations into AXL molecular signalling networks and robust predictive biomarkers are warranted to select patients who could receive clinical benefit and to avoid potential toxicities.

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Section: Axl-targeted Therapiesmentioning

confidence: 99%

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

2019

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“…8 Accordingly, several studies have introduced multi-step culture systems, 9,10 consisting of progenitor expansion, MK differentiation, and platelet generation steps, to obtain an optimal yield from platelet production. An in vitro study 11 suggested that platelet yield is dominantly determined by megakaryocyte number, therefore, cell expansion is a crucial stage for achieving a large number of platelet. 9 Successful expansion of MK progenitors in lab-scale culture systems has been welldescribed.…”

Section: Introductionmentioning

confidence: 99%

Large‐scale culture of a megakaryocytic progenitor cell line with a single‐use bioreactor system

Nurhayati

Ojima

Dohda

et al. 2017

Biotechnology Progress

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The increasing application of regenerative medicine has generated a growing demand for stem cells and their derivatives. Single-use bioreactors offer an attractive platform for stem cell expansion owing to their scalability for large-scale production and feasibility of meeting clinical-grade standards. The current work evaluated the capacity of a single-use bioreactor system (1 L working volume) for expanding Meg01 cells, a megakaryocytic (MK) progenitor cell line. Oxygen supply was provided by surface aeration to minimize foaming and orbital shaking was used to promote oxygen transfer. Oxygen transfer rates (k a) of shaking speeds 50, 100, and 125 rpm were estimated to be 0.39, 1.12, and 10.45 h , respectively. Shaking speed was a critical factor for optimizing cell growth. At 50 rpm, Meg01 cells exhibited restricted growth due to insufficient mixing. A negative effect occurred when the shaking speed was increased to 125 rpm, likely caused by high hydrodynamic shear stress. The bioreactor culture achieved the highest growth profile when shaken at 100 rpm, achieving a total expansion rate up to 5.7-fold with a total cell number of 1.2 ± 0.2 × 10 cells L . In addition, cells expanded using the bioreactor system could maintain their potency to differentiate following the MK lineage, as analyzed from specific surface protein and morphological similarity with the cells grown in the conventional culturing system. Our study reports the impact of operational variables such as shaking speed for growth profile and MK differentiation potential of a progenitor cell line in a single-use bioreactor. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:362-369, 2018.

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“…Nicotinamide increases the polyploidization and proplatelet formation by increasing TP53 activity [88]. Src-family kinases inhibit megakaryocyte proliferation and differentiation and either a Src inhibitor or a multi-kinase inhibitor induces polyploidization [89,90]. Rho A and the downstream Rho-associated protein kinase (ROCK) contributes to actin function, and ROCK inhibitors have been reported to enhance megakaryocyte polyploidization and proplatelet formation [91][92][93][94].…”

Section: Development Of Drugs That Contribute To Megakaryocyte Maturamentioning

confidence: 99%

Generation and manipulation of human iPSC-derived platelets

Sugimoto

Eto

2021

Cell. Mol. Life Sci.

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The discovery of iPSCs has led to the ex vivo production of differentiated cells for regenerative medicine. In the case of transfusion products, the derivation of platelets from iPSCs is expected to complement our current blood-donor supplied transfusion system through donor-independent production with complete pathogen-free assurance. This derivation can also overcome alloimmune platelet transfusion refractoriness by resulting in autologous, HLA-homologous or HLA-deficient products. Several developments were necessary to produce a massive number of platelets required for a single transfusion. First, expandable megakaryocytes were established from iPSCs through transgene expression. Second, a turbulent-type bioreactor with improved platelet yield and quality was developed. Third, novel drugs that enabled efficient feeder cell-free conditions were developed. Fourth, the platelet-containing suspension was purified and resuspended in an appropriate buffer. Finally, the platelet product needed to be assured for competency and safety including non-tumorigenicity through in vitro and in vivo preclinical tests. Based on these advancements, a clinical trial has started. The generation of human iPSC-derived platelets could evolve transfusion medicine to the next stage and assure a ubiquitous, safe supply of platelet products. Further, considering the feasibility of gene manipulations in iPSCs, other platelet products may bring forth novel therapeutic measures.

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BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells

Cited by 10 publications

References 33 publications

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Large‐scale culture of a megakaryocytic progenitor cell line with a single‐use bioreactor system

Generation and manipulation of human iPSC-derived platelets

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