Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OTT1(RBM15) was originally described as a 5' translocation partner of the MAL(MKL1) gene in t(1,22)(p13;q13) infant acute mega karyocytic leukemia. OTT1 has no established physiological function, but it shares homology with the spen/Mint/SHARP family of proteins defined by three amino-terminal RNA recognition motifs and a carboxyl-terminal SPOC (Spen paralog and ortholog carboxyl-terminal) domain believed to act as a transcriptional repressor. To define the role of OTT1 in hematopoiesis and help elucidate the mechanism of t(1,22) acute megakaryocytic leukemia pathogenesis, a conditional allele of Ott1 was generated in mice. Deletion of Ott1 in adult mice caused a loss of peripheral B cells due to a block in pro/pre-B differentiation. There is myeloid and megakaryocytic expansion in spleen and bone marrow, an increase in the Lin(-)Sca-1(+)c-Kit(+) compartment that includes hematopoietic stem cells, and a shift in progenitor fate toward granulocyte differentiation. These data show a requirement for Ott1 in B lymphopoiesis, and inhibitory roles in the myeloid, megakaryocytic, and progenitor compartments. The ability of Ott1 to affect hematopoietic cell fate and expansion in multiple lineages is a novel attribute for a spen family member and delineates Ott1 from other known effectors of hematopoietic development. It is plausible that dysregulation of Ott1-dependent hematopoietic developmental pathways, in particular those affecting the megakaryocyte lineage, may contribute to OTT1-MAL-mediated leukemogenesis.
 ...
PMID:Ott1(Rbm15) has pleiotropic roles in hematopoietic development. 1737 72

Sorafenib, a molecular-targeted agent that inhibits tumor cell proliferation and angiogenesis by inhibiting RAF serine-threonine kinase and VEGF, PDGF, Flt-3, c-Kit receptor tyrosine kinase, was approved in Europe and North America in 2007 and in Japan on May 20, 2009. In the 10 months since its approval, sorafenib has been prescribed for more than 3,700 patients with advanced hepatocellular carcinoma (HCC), and its efficacy has been confirmed in many cases. According to the consensus statements of the Japan Society of Hepatology in 2010, sorafenib is recommended for advanced HCC with extrahepatic spread or major vascular invasion such as invasion of the 1st branch of the portal vein or the main portal branch of the portal vein in patients with Child-Pugh A liver function. In addition to that, transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) refractory HCC patients with Child-Pugh A liver function are also candidates of sorafenib monotherapy as a second-line treatment option. To date, 15 cases with complete remission (CR) to sorafenib in metastatic advanced HCC patients have been reported in Japan, an event that is rarely reported in other countries. Of the 90 cases treated by ourselves, 2 achieved CR. Factors indicating systemic cancer spread, including multiple liver lesions, lymph node metastases, adrenal metastases, lung metastases and vascular invasion, were completely absent in both cases of CR by 2 and 1 year, respectively. Similarly, three tumor markers (AFP, PIVKA-II, and AFP-L3) completely returned to normal values. Although cases of CR are rare, it seems that there might be racial differences in terms of gene mutations. Clinical trials for other molecular-targeted agents, including sunitinib, brivanib, or linifanib, are ongoing and their outcomes are eagerly awaited. According to a subanalysis of the SHARP study, it is expected that sorafenib in combination with resection, ablation, TACE or HAIC will markedly prolong the overall survival in early-, intermediate- and advanced- stage HCCs.
 ...
PMID:Positioning of a molecular-targeted agent, sorafenib, in the treatment algorithm for hepatocellular carcinoma and implication of many complete remission cases in Japan. 2061 99