1/6/2024 0 Comments Flowjo ashlandEighty-five percent of GIST contains either the mutant KIT or mutant PDGFR-alpha. KIT and PDGFR-alpha belong to the type III receptor tyrosine kinase family, members of which can lead to the occurrence of several cancers. Gain-of-function mutated forms of KIT and PDGFR-alpha are two well-known oncogenic proteins which play pivotal role in the development and maintenance of GIST. The 5-year relative survival rate for GIST for all stages combined is 83%. The incidence of GIST is 0.70 per 100,000 people per year in the USA based on data from 2001 to 2015. As the majority of GIST have relatively low mitotic rate, grading of cancer stage is only determined by mitotic count on an area that shows the highest level of mitotic activity. It metastasizes principally to liver and peritoneal surfaces, rarely to lymph nodes, lung and bone. In the clinical practice, GIST can recur years after initial tumor excision, and demonstrate ability of distant metastasis. It originates from the interstitial cells of Cajal which lines in the wall of GI tract and extends towards mucosa or/and serosa. Gastrointestinal stromal tumor (GIST) is a type of soft tissue tumor that mainly occurs along the gastrointestinal (GI) tract. SCF-DM1 is an effective drug candidate to treat imatinib-sensitive and -resistant GIST. RhSCF is a convenient and effective vector for drug delivery to KIT positive GIST cells. In xenograft mouse model, SCF-DM1 showed favorable efficacy and safety profiles. It induced apoptosis and cell cycle arrest in GIST cells. SCF-DM1 was effective in inhibiting imatinib-sensitive and -resistant GIST cell lines and primary tumor cells, with IC 50 values of < 30 nM. It was then conjugated with DM1, and the conjugated product SCF-DM1 was evaluated using in vitro cell-based assays and in vivo xenograft mouse model. coli cells and further purified with Ni–NTA Sepharose and Phenyl Sepharose. Recombinant human SCF (rhSCF) was expressed in E. Here, we produced a SCF-emtansine drug conjugate (SCF-DM1) with favorable drug efficacy towards GIST cells. However, drug resistance often develops during the therapeutic treatment. Small molecule kinase inhibitor imatinib is effective in prolonging the survival of GIST patients by targeting KIT. The majority of GIST cases carry oncogenic forms of KIT, the receptor for stem cell factor (SCF). Gastrointestinal stromal tumor (GIST) is a rare type of cancer that occurs in the gastrointestinal tract.
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