Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012833 (dizziness)
 9,689 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imatinib mesylate targets the adenosine triphosphate (ATP)-binding sites of the protein tyrosine kinase domains associated with Bcr-abl, the platelet-derived growth factor (PDGF) and c-kit. In idiopathic myelofibrosis (IMF) PDGF is considered to be one of the growth factors responsible for the development of bone marrow fibrosis. Recently, it has been shown that imatinib has antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia. Treatment with imatinib alone in IMF has been associated with significant side effects. In this study, the safety and efficacy of imatinib therapy in IMF, either administered as a single agent or in combination with hydroxyurea (HU) and/or alpha-interferon (IFN-alpha) are evaluated. Eleven patients (median age, 63 years; range, 33-82 years) with IMF (n = 8) or postpolycythemic myelofibrosis (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or IFN (n = 7) before study entry. In all but one patient, treatment with these agents was discontinued when imatinib therapy was instituted. One patient continued IFN when treatment with imatinib was started. Imatinib was given at a dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients have been followed for a median period of 2 months (range, 0.5-12 months). Treatment with imatinib has been stopped in six patients (55%), because of overt side effects (n = 4), recurrence of transitory dizziness and visual defects owing to a rising platelet count (n = 1), or the occurrence of an acute subdural hemorrhage that was evacuated without neurological deficits (n = 1). In nine patients imatinib treatment was followed by a rise in leukocyte and platelet counts that required combination with HU or IFN. The combined treatment modalities were followed by a rapid decrease in cell counts and were well tolerated apart from IFN side effects. A beneficial effect of imatinib was documented in three patients. It is concluded that leukocytosis and thrombocytosis are seen in most patients with myelofibrosis during treatment with imatinib. Combination therapy with HU or IFN seems safe and well tolerated and followed by a decrease in disease activity. A subgroup of patients in an early disease phase might benefit from imatinib therapy alone.
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PMID:Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis. 1463 3

We report herein the case of 64-year-old man with gastrointestinal stromal tumor (GIST), who was treated by partial resection of the duodenum after preoperative transarterial embolization. He presented to our hospital with a history of tarry stools, dizziness, and severe anemia (hemoglobin, 7.5 g/dl). Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the second portion of the duodenum. The presence of the tumor was subsequently confirmed by double-contrast gastrointestinal radiography and abdominal computed tomography. Super-selective angiography showed tumor staining fed from the anterior and posterior superior pancreaticoduodenal arteries, and the inferior pancreaticoduodenal artery. Two weeks after transarterial embolization through these vessels, the tumor size was found to have shrunk to 40% of its original size. Partial resection of the duodenum was performed and absence of tumor cells at the surgical margin was confirmed by intraoperative frozen-section examination. Histopathological examination revealed that the duodenal submucosal tumor consisted of spindle cells, and immunohistochemical analysis revealed positive tumor staining for c-kit protein, CD34 and alpha-smooth muscle actin (SMA), and negative staining for desmin and S-100; the positivity rate for MIB-1 staining was 2.2%. Based on these findings, the tumor was diagnosed as a GIST of low-grade malignancy, classified as the muscular type. It is considered that preoperative treatment of duodenal GISTs, such as transarterial embolization, may be useful for reducing the extent of resection, from pancreaticoduodenenctomy to a partial resection.
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PMID:Partial resection of the second portion of the duodenum for gastrointestinal stromal tumor after effective transarterial embolization. 1636 49

PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this Phase I study was to evaluate the safety, tolerability, biologic activity and pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous dosing schedule in patients with primary refractory or relapsed acute myeloid leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK monotherapy was ineffective could receive PTK/ZK combined with standard induction chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated according to standard bone marrow and peripheral blood criteria. At 1000 mg b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and anorexia were observed. Other adverse events related to PTK/ZK were dizziness, weakness, fatigue, diarrhea and pruritus; these were generally mild and reversible. Pharmacokinetic data showed that steady state was reached by day 14, there was no accumulation with repeat dosing and there was no significant increase in exposure at steady state beyond the maximum tolerated dose (MTD). Complete remission was observed in five of 17 AML patients treated with PTK/ZK combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally b.i.d. The drug is generally well tolerated and can be given in combination with chemotherapy for patients with MDS and AML.
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PMID:Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. 1661 23

A 65-year-old man is presented here with a huge mass of 13 cm in diameter in the left upper abdomen. Histopathologic assessment of endoscopic forceps biopsy revealed a c-kit positive gastrointestinal storomal tumor (GIST) of the stomach. Abdominal computed tomography (CT) showed a direct invasion to the pancreas. Imatinib mesilate was administered as neoadjuvant therapy according to the NCCN Guidelines. Imatinib mesilate therapy was stopped within 2 weeks because of adverse events such as Grade 2 of facial edema and dizziness. However, no hematological adverse event was shown. After three months of treatment (relative dose intensity was 87.5%), CT revealed a reduction in tumor diameter of 35.6% and showed no longer a direct invasion to the pancreas. The radical operation was considered feasible and partial gastrectomy was performed. The tumor was well encapsulated and radical surgery was possible without rupture. Adjuvant therapy was not performed. The patient has now been in good health without a recurrence for three months after the surgery.
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PMID:[Neoadjuvant therapy with imatinib mesilate for gastrointestinal stromal tumor of the stomach before subsequent successful surgical resection]. 1721 33

Acute basophilic leukemia (ABL) is a rare and poorly characterized form of leukemia. The case of a 65-year-old male who complained of dizziness, maculopapular skin lesions and melena is described in the current report. A gastroscopy was conducted and indicated a gastric antral ulcer. The diagnosis of ABL was determined due to characteristic cytomorphological features, the myeloid immunophenotype of the blast cells (identified to be positive for cluster of differentiation [CD]25 and CD123) in addition to the absence of the Philadelphia chromosome and a c-kit D816V mutation. The patient initially demonstrated clinical improvement as a result of chemotherapy, however, subsequently deteriorated. The gastric and skin manifestations of ABL may be associated with excessive histamine release from basophilic cells. Thus, the administration of H1- and H2-receptor antagonists, proton pump inhibitors and steroids is proposed in order to minimize these associated complications.
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PMID:Acute basophilic leukemia presenting with maculopapular rashes and a gastric ulcer: A case report. 2536 19