• Korean Journal of Head & Neck Oncology
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• v.38 no.1
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• pp.1-9
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• 2022

Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.188-198
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• 2013

Over the past decade, several kinase inhibitors have been approved based on their clinical benefit in cancer patients. Unfortunately, in many cases, patients develop resistance to these agents via secondary mutations and alternative mechanisms. To date, several major mechanisms of acquired resistance, such as secondary mutation of the epidermal growth factor receptor (EGFR) gene, amplification of the MET gene and overexpression of hepatocyte growth factor, have been reported. This review describes the recent findings on the mechanisms of primary and acquired resistance to EGFR tyrosine kinase inhibitors and acquired resistance to anaplastic lymphoma kinase inhibitors, primarily focusing on non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.77 no.2
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• pp.49-54
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• 2014

The rapid development of targeted therapies has enormously changed the clinical management of lung cancer patients over the past decade; therefore, molecular testing, such as epidermal growth factor receptor (EGFR) gene mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, is now routinely used to predict the therapeutic responses in lung cancer patients. Moreover, as technology and knowledge supporting molecular testing is rapidly evolving, the landscape of targetable genomic alterations in lung cancer is expanding as well. This article will summarize the current state of the most commonly altered and most clinically relevant genes in lung cancer along with a brief review of potential future developments in molecular testing of lung cancer.

• Journal of Life Science
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• v.28 no.12
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• pp.1469-1476
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• 2018

Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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• pp.14-19
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• 2020

Lung cancer remains the most common cause of cancer-related deaths worldwide. Although there are many possible treatments, including targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.220-227
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• 1998

The clinical and pathological features of 35 cases of anaplastic thyroid cancer were studied. These tumors occurred in 12 men and 23 women ranging in age from 19 to 83 years(mean age; 61.7 years). A rapidly enlarging thyroid mass was the most common presentation. The duration of the presence of mass varied from 20 days to 12 months with an average of 2.7 months. Systemic metastasis at the time of initial examination was found in 14 patients(40.0%) and the lung was the most common site of involvement. The overall rate of distant metastasis was about 65.7%. The tumors were subdivided morphologically into giant cell type of 10 cases, spindle cell type of 7 cases, epidermoid cell type of 1 cases, and mixed giant cell and spindle cell type of 5 cases. The mean survival period of 6 among 35 patients who had biopsy alone was 1.4 months. The 22 patients underwent the incomplete combined treatment modalities (palliative surgery with or without chemotherpy or radiation therapy) survived for a mean period of 3.0 months, among them, 7 patients who had surgery combined with chemotherapy and radiation therapy showed mean survival period of 3.7 months. The mean survival of 7 patients who had complete combined treatment modality(curative surgery combined with chemotherapy and hyperfractionated radiation therapy) was 6.6 months, only one patient survived for 21 months and one patient has been alive for 1 month after operation, and the others survived for a mean period of 4.8 months. So far, as of July 31, 1998, 34 patients among 35 were died(one has been survived for 1 month) despite the various treatment modalities, and the main cause of death were failure of local control and systemic metastasis. None of the various treatment modalities gave consistently favourable results. However, a combination of surgery, radiation therapy and chemotherapy seemed to have a slight positive effect on survival. Furthermore, the aggressive treatment modalities will be indicated only in the early diagnosed and minimal cases.

• Journal of Korean Traditional Oncology
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• v.23 no.1
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• pp.23-32
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• 2018

Objective: The purpose of this study is to report the case of a patient with non-small cell lung adenocarcinoma (NSCLC) with anaplastic lymphoma kinase (ALK) mutation treated by Samchilchoongcho-Jung in conjunction with Crizotinib. Methods: An NSCLC patient diagnosed with multiple pleural and lymph nodes metastasis has been taking Crizotinib (500 mg/day) since January 2014. The patient has been treated with Samchilchoongcho-Jung (1,500 mg/day) since June 2014. The tumor size was measured by computed tomography (CT) and laboratory analysis was conducted. Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Results: After combining treatment, stable disease was shown on CT. The tumor marker (CEA, Cyfra 21-1) levels were maintained. NCI-CTCAE 5.0 showed no adverse events. Conclusion: This case study suggests that Samchilchoongcho-Jung may contribute to tumor response, in conjunction with Crizotinib on the treatment of patients with NSCLC.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Tuberculosis and Respiratory Diseases
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• v.75 no.5
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• pp.181-187
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• 2013

The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

• Journal of Gastric Cancer
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• v.15 no.1
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• pp.64-67
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• 2015

Inflammatory myofibroblastic tumors (IMTs) of the stomach are extremely rare in adults, and their oncologic prognosis is not well understood. We present a 28-year-old man with a proximal gastric IMT. The patient visited the emergency department of Yeouido St. Mary's Hospital with syncope and hematemesis. Hemoglobin levels were <5.5 g/dl. Gastric fibroscopy showed a protruding mass $4{\times}4cm$ in size, with central ulceration on the posterior wall of the fundus and diffuse wall thickening throughout the cardia and anterior wall of the upper body. Endoscopic biopsy revealed indeterminate spindle cells, along with inflammation. Given the risk of rebleeding, an operation was performed despite the uncertain diagnosis. Because the mass was circumferential, laparoscopic proximal gastrectomy and double-tract anastomosis were performed to ensure a safe resection margin. The pathological diagnosis was consistent with an IMT originating from the stomach, although the tumor was negative for anaplastic lymphoma kinase gene mutation.