Resistant KIT mutations have hindered the development of KIT kinase inhibitors for treatment of patients with systemic mastocytosis. The goal of this research was to characterize the synergistic effects of a novel combination therapy involving inhibition of KIT and calcineurin phosphatase, a nuclear factor of activated T cells (NFAT) regulator, using a panel ofKIT-mutantmast cell lines. The eff...

The degree of redundancy between thrombopoietin (Tpo) and steel factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors. Double mutant c-Mpl;Kit mice exhibited reduced viability, making up only 2% of the offspring from c-Mpl;Kit intercrosses. The thrombocytopenia and megakaryocytopenia character...

Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is classified into three forms: well- (G1), intermediately (G2) (more benign diseases), and poorly (G3) differentiated (malignant) forms. We assess a correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore their potentia...

The co-expression of KIT receptor and its ligand stem cell factor (SCF) has been reported in biopsy specimens of Merkel cell carcinoma (MCC). However, the functional role of SCF/KIT in the pathogenesis of this aggressive tumor has not been elucidated. The present study reports expression and effects of SCF and KIT in the Merkel cell carcinoma cell line MCC-1 in vitro. SCF and KIT were endogenou...

In Low Earth Orbit, it is possible to use the ambient plasma and geomagnetic field exchange momentum with Earth's magnetosphere without using propellant. A device that allows an efficient electrodynamic tether (EDT), a long conductor attached satellite. EDT technology has been demonstrated in several past missions, being Plasma Motor Generator mission (NASA 1993) one of most successful. Neverth...

Mutations of c-KIT causing spontaneous activation of the KIT receptor kinase are associated with sporadic adult human mastocytosis (SAHM) and with human gastrointestinal stromal tumors. We have classified KIT-activating mutations as either "enzymatic site" type (EST) mutations, affecting the structure of the catalytic portion of the kinase, or as "regulatory" type (RT) mutations, affecting regu...

The receptor-type tyrosine kinase, c-kit is expressed in hematopoietic stem cells (HSC), myeloid, and lymphoid precursors. In c-kit ligand-deficient mice, absolute numbers of HSC are mildly reduced suggesting that c-kit is not essential for HSC development. However, c-kit- HSC cannot form spleen colonies or reconstitute hematopoietic functions in lethally irradiated recipient mice. Based on in ...

This research was carried out in rural Nepal to explore how different categories of birth attendants at home deliveries accepted and used clean home delivery kit (CHDK) and its contents, including hand-washing practices, during delivery and preparations for birth. In-depth interviews were conducted to collect information from 51 women-both users and non-users of the kit. The respondents were in...