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)

The effects of recombinant mouse stem cell factor (rmSCF) on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in the mossy fiber (MF)-CA3 pathway were examined in mouse hippocampal slices by recording field EPSPs. When PPF was measured before and 30 min after tetanic stimulation, the initial PPF positively correlated with the amplitude of LTP and negatively correlated with changes in PPF (PPF after LTP minus initial PPF), indicating a presynaptic component in MF-CA3 LTP. Bath application of rmSCF for 30 min also produced negative correlation between initial PPF and changes in PPF after rmSCF, suggesting common mechanisms of the LTP- and rmSCF-induced modulation of PPF. The rmSCF-induced negative correlation was abolished by simultaneous perfusion with K252a, a receptor tyrosine kinase inhibitor, and by wortmannin, a phosphatidylinositol-3'-kinase inhibitor. Although SCF activates phospholipase A(2) (PLA(2)) and diacylglycerol (DAG) lipase to produce arachidonic acid (AA) in mast cells, mepacrine, a PLA(2) inhibitor, but not RHC80267, a DAG lipase inhibitor, abolished the negative correlation. The induction of LTP was prevented by perfusion with rmSCF started 30 min before tetanus, while preincubation of slices with antibody for SCF receptor, c-kit, blocked LTP, suggesting that the intrinsic SCF is involved in the induction of LTP and the blockade of LTP by rmSCF might be due to an occlusion of SCF/c-kit signaling. In addition, since c-kit is expressed on the postsynaptic CA3 neurons but not on the MF terminals in mice, effects of rmSCF on PPF may be mediated by the PLA(2)-induced AA acting as a retrograde messenger.
 ...
PMID:Stem cell factor modulates paired-pulse facilitation and long-term potentiation in the hippocampal mossy fiber-CA3 pathway in mice. 1213 20

Granulocytic sarcoma mimicking a synchronous second primary neoplasm (SPN) constitutes a diagnostic and therapeutic challenge particularly in elderly patients. We report on a 75-year-old female presenting with a Core-binding Factor (CBF) AML of M4eo subtype. The patient also had jaundice, highly elevated bilirubin, lipase, alkaline phosphatase (AP), CA 19-9, and a pancreatic mass highly suspicious of infiltrating pancreatic carcinoma. However, a biopsy demonstrated granulocytic sarcoma. Since the patient had no comorbidities and had been in excellent performance status until the diagnosis of AML, induction chemotherapy was initiated, with subsequent normalization of bilirubin, CA 19-9, lipase and AP. Complete hematologic remission of AML was attained and the pancreatic mass could not be detected anymore. Retrospective analysis of the c-kit protooncogene did not disclose activating mutations of exons 8 or 17. Following one consolidation treatment, the patient remained in excellent health until relapse occurred 7 months later and she succumbed to AML. In conclusion, AML can rarely mimic the clinical picture of pancreatic cancer. The initially good response of this CBF leukemia highlights the principal usefulness of aggressive induction chemotherapy also in older AML patients, if they are carefully selected not only according to biological risk factors such as cytogenetics, but also to "host factors" (good performance status, lack of comorbidities, etc.).
 ...
PMID:Granulocytic sarcoma of Core-binding Factor (CBF) acute myeloid leukemia mimicking pancreatic cancer. 1845 26

Lysosomal acid lipase (LAL) is a key enzyme that cleaves cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. Genetic ablation of the lal gene (lal(-/-)) in mice has resulted in a systemic increase of macrophages and neutrophils, causing severe inflammation and pathogenesis in multiple organs. We hypothesized that aberrant growth and differentiation of myeloid cells in lal(-/-) mice arises from dysregulated production of progenitor cells in the bone marrow. Indeed, lal(-/-) mice displayed increased numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells and granulocyte-macrophage precursors (GMP). Increased high proliferative potential colony-forming cells (HPP-CFC) were enumerated from cultured lal(-/-) bone marrow cells, as were significantly more CFU-GM, CFU-G, and CFU-M colonies. As a consequence, lal(-/-) mice developed significant myeloid infiltration, particularly with CD11b+/Gr-1+ myeloid-derived suppressive cells in multiple organs. Both decreased apoptosis and increased proliferation contribute to the systemic increase of myeloid cells in lal(-/-) myeloid cells. These lal(-/-) CD11b(+)/Gr-1(+) cells displayed suppressive activity on T cell proliferation and function in vitro. Bone marrow chimeras confirmed that the myeloproliferative disorder in lal(-/-) mice was primarily attributable to autonomous defects in myeloid progenitor cells, although the hematopoietic microenvironment in the lal(-/-) mice did not support hematopoiesis normally. These results provide evidence that LAL is an important regulator of myelopoiesis during hematopoietic development, differentiation, and homeostasis.
 ...
PMID:Critical roles of lysosomal acid lipase in myelopoiesis. 2034 41

Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis.
...
PMID:Pazopanib-Induced Severe Acute Pancreatitis. 2646 70