• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.158-164
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• 2005

Purpose: The serine/threonine kinase Akt was described to inhibit apoptosis in cancer. This study was to examine the effect of Gleevec on head and neck squamous cell carcinoma(HNSCC) through the mechanism of Akt. Experimental Design: Gleevec was introduced into the HNSCC cell lines UMSCC10B, HN12 and HN30 in a range of concentrations. Cell viability was assessed by clonogenic survival analysis. Targets of Gleevec(PDGFR, c-Kit, and c-Abl) were evaluated by Western blot. HNSCC tissue samples were stained for PDGFR, c-Kit and phosphorylated Akt. Akt phosphorylation following Gleevec treatment was assessed using Western blot. Akt siRNA was used to as the positive control. Results: Colony forming efficiency decreased with an increase in concentration of Gleevec. Expressions of PDGFR, c-Kit, and c-Abl were observed in HNSCC cells. Immunohistochemistry confirmed high expression of PDGFR, c-Kit, and p-Akt in human HNSCC tissues. Akt kinase activity was significantly inhibited with increasing concentration of Gleevec in HNSCC cells, and near complete dephosphorylation of Akt was observed at $6{\mu}M$ of Gleevec in the UMSCC10B and HN30 cell lines. Conclusions: Gleevec at clinically comparable concentrations caused a dose dependant decrease in HNSCC survival. The decreased cell survival was related to the inhibition of Akt kinase activity and dephosphorylation of Akt. Akt signaling pathway may be a relevant target for Gleevec in treating HNSCC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.913-921
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• 2005

In this study, we investigated gene expression patterns induced by Ailanthus altissima extract and compared it with Gleevec, a well-known anti-leukemia drug, in K562 chromic leukemia cells. Ailanthus altissima extract(100 ug/ml) and Gleevec(50 ug/ml) were treated to cells for 1h, 2h, 4h, and 16h and total RNA was extracted. Gene expressions were evaluated using cDMA microarray, in which 24,000 genes were spotted. Hierarchical clustering analysis showed that expression of genes included in two clusters were increased or decreased time dependently by both Ailanthus altissima extract and Gleevec. Genes included in another cluster were induced by Ailanthus altissima extract but not by Gleevec. In biological process analysis, expression of genes involved in apoptosis, growth arrest and DNA-damage were increased, but genes stimulating cell cycle were decreased. This study provides comprehensive comparison of the patterns of gene expression changes induced by Ailanthus altissima extract and Gleevec in K-562 leukemia cells.

• BMB Reports
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• v.38 no.6
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• pp.725-738
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• 2005

Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a $1\;{\mu}M$ imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.99-109
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• 2015

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

• Korean journal of aerospace and environmental medicine
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• v.30 no.2
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• pp.80-82
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• 2020

Gastrointestinal Stromal Tumors (GISTs) are relatively uncommon soft tissue sarcomas that can be located in any part of the digestive system. GISTs originate in specialized nerve cells located in the walls of the digestive system. This case report is about a 53-year-old airman who was recently diagnosed as peritoneal GISTs. He got a surgical removal of the tumor and chemotherapy, including imatinib (Gleevec^®). Although his GISTs have shown excellent clinical progress, he still needs ongoing treatment. This case involves an airline pilot applicant for Class-I medical certification who has had GISTs under chemotherapy.

• Korean journal of aerospace and environmental medicine
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• v.31 no.3
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• pp.82-83
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• 2021

Chronic myeloid leukemia (CML) is myeloproliferative neoplasm associated with a characteristic chromosomal translocation (bcr-abl) called Philadelphia chromosome which plays a key role in the pathogenesis. Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. During this phase, patients are well tolerated and have few symptoms. But untreated, over the course of several years progresses to an accelerated phase and ultimately to a blast crisis, the terminal phase. CML is largely treated with targeted drug therapy called tyrosine-kinase inhibitors (TKIs) which have led to dramatically improved long-term survival rates since 2001. These drugs became standard treatment of this disease and allow most patients to have much better quality of life when compared to the former chemotherapy drugs and the bone marrow transplantation. Imatinib (Gleevec or Glivec, Norvatis) was the first of these TKIs and found to inhibit the progression of CML in the majority of patients (65%-75%) sufficiently to achieve remission. Since the advent of imatinib, CML has become the first neoplasm in which a medical treatment can give to the patient a normal life expectancy.

• Health Policy and Management
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• v.20 no.1
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• pp.64-86
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• 2010

Korea has had problems with the price and supply of essential drugs such as Gleevec for leukemia, Fuzeon for HIV/AIDS, and Tamiflu for both avian flu and swine flu. The shortage or refusal of patented drugs supply is imposing a heavy burden in not only developing countries but also developed countries. Thinking over the serious results, we need to concern about the limited access to patented drugs by multinational drug companies' patent monopoly especially for pandemic and life threatening diseases. The effective response regarding to pandemic and life threatening diseases. The effective response regarding to pandemic situation requests collaborative and unbiased provisions of all countries in the world, however, sometimes patent monopoly may hinder the efforts. Compulsory licensing has been considered to be a useful alternative to the abuse of patent rights. However, the Korean experiences of compulsory licensing have left some controversial issues in connection with the availability of it in Korea. 'Flexibility' allowed in TRIPS and Doha Declaration has not come into effect in Korea for several reasons. Although the situation shows the limitations of compulsory licensing as a pharmaceutical supply policy, it is clear that compulsory licensing still has the possibilities of enhancing the access to medicines of all countries in need. Through searching the institutionalization process and experiments of compulsory licensing in Korea, this article explores the possibilities and the limits.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.423-426
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• 2005

Imatinib-mesylate (Gleevec, Glivec) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib is also used to treat patients with c-kit (CD 117)-positive unresectable tumors, or metastatic malignant gastrointestinal stromal tumors, or both. Imatinib is a welltolerated drug with few side effects. However, it has been associated with gastrointestinal irritation, fluid retention and edema, skin rashes, depigmentation, hepatotoxicity, hemorrhage, and hematological toxicity (anemia, neutropenia, and thrombocytopenia). In addition, imatinib has been associated with dyspnea and cough, which are mainly secondary to the pleural effusion and pulmonary edema, which represent local or general fluid retention. These events appear to be dose related and are more common encountered in the elderly. However, there has been no report of hypersensitivity pneumonitis associated with imatinib-mesylate in Korea. We report a case of 51-year old woman who developed hypersensitivity pneumonitis that might have been induced by imatinib-mesylate during the treatment of a gastrointestinal stromal tumor.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.40-46
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• 2005

Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1：1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.