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)

Among gynecologic malignancies, ovarian carcinoma is the most frequent cause of death, with the majority of patients presenting at advanced stage. There is a high rate of recurrence despite first-line chemotherapy. Sarcoma of the uterus, while accounting for a small percent of uterine cancers, is also associated with a high-recurrence rate and poor overall survival. Therefore, the development of novel treatment strategies is paramount. Imatinib mesylate (Gleevec; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a tyrosine kinase inhibitor with activity against abl, c-kit, and platelet derived growth factor receptor (PDGFR), and is approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumor. Preclinical data provides evidence for c-kit and PDGFR expression in ovarian epithelial carcinomas and uterine sarcomas and have led to clinical trials evaluating the use of imatinib in these malignancies. Additionally, inhibition of PDGFR signaling has been proposed as an effective mechanism of chemotherapy by lowering tumor interstitial fluid pressure. Recent data have also suggested benefit with metronomic scheduling of cytotoxic agents at lower doses at more frequent dosing intervals, in combination with other targeted therapies. While activity of this agent remains to be established, further studies of imatinib in gynecologic malignancies are warranted, to demonstrate not only single-agent activity and the enhancement of cytotoxicity of other antineoplastic agents.
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PMID:Imatinib mesylate and its potential implications for gynecologic cancers. 1571 93

Sarcoma of the stomach is a rare histological entity. These differentiated mesenchymal tumors do not differ clinically from other gastric cancers. Endoscopic ultrasonography is the preferred means of exploration because it determines the existence of a submucosal lesion and provides guidance in determining its type. Certainty of diagnosis requires pathologic and immunohistochemical examinations of the surgical specimen. Malignant gastric stromal tumors are the first differential diagnosis of sarcoma of the stomach. They can be better characterized by testing their expression of the c-kit protein. Histological confirmation of malignancy sometimes remains difficult. Locoregional invasion and distant metastases confirm malignancy. Treatment is essentially surgical. Prognosis depends on tumor size, extension, rupture and histological grade.
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PMID:[Gastric sarcoma]. 1758 40

Purpose. To study the evolution of concepts concerning gastrointestinal stromal tumours (GISTs) over 30 years.Discussion. GISTs have been, for more than 30 years, the subject of considerable controversy regarding their line of differentiation as well as the prediction of their behaviour. Furthermore, once they spread within the peritoneal cavity, they are extremely hard to control. The recent findings of c-Kit mutations and the immunohistochemical detection of the product of this gene, KIT or CD117, in the mainly non-myogenic subset of this family of tumours, has led to a reappraisal of this group of lesions, which, with some exceptions, is now thought to be derived from the interstitial cells of Cajal, and this has facilitated a clearer definition of their pathological spectrum. In this article, we review chronologically the evolution of the concept of GIST with the gradual application of electron microscopy, immunohistochemistry, DNA ploidy analysis. We discuss the impact of these techniques on the pathological assessment and clinical management of GISTs.
Sarcoma 1998
PMID:Gastrointestinal stromal tumours: an update. 1852 Dec 45

Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines. Therapeutics that target angiogenesis showed antitumor activity. The small molecule inhibitor axitinib, which targets angiogenesis by inhibiting the VEGFR and PDGFR families and c-Kit, inhibited cell cycle progression and induced apoptosis in vitro, as well as having significant antitumor activity against MLS 1765 myxoid liposarcoma xenografts in mice. Axitinib also displayed synergistic antitumor activity in vitro when combined with the potassium channel ionophore salinomycin or the BH3 mimetic ABT-737. Another angiogenesis-targeting therapeutic, 4EGI-1, which targets the oncoprotein eIF4E, significantly decreased angiogenic ligand expression by myxoid liposarcoma cells and reduced tumor cell growth. To verify this oncogenic addiction to angiogenic pathways, we utilized VEGFR-derived ligand traps and found that autocrine VEGFR signaling was crucial to myxoid liposarcoma cell survival. Overall, these findings suggest that autocrine angiogenic signaling through the VEGFR family is critical to myxoid liposarcoma cell survival and that further study of axitinib as a potential anticancer therapy is warranted.
Sarcoma 2016
PMID:Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma. 2782 37