• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3239-3245
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• 2012

Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.292-301
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• 2018

Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

• Journal of Chest Surgery
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• v.43 no.3
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• pp.320-323
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• 2010

Adenoid cystic carcinoma is a relatively rare tumor that usually arises in the parotid and submandibular salivary glands. The initial management is surgical, and this is often combined with post-operative radiotherapy, but local relapse is common and distant metastasis is not infrequent. We experienced the case of a 59 years old male who had been previously operated on for a primary submandibular salivary cyst, and he then had a distant pulmonary metastasis 9 years later. We operated on him with performing a wedge resection on the left lower lobe for the metastatic lesion, and he hasn't had any evidence of tumor recurrence for 84 months after the second operation.

• Journal of Chest Surgery
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• v.12 no.4
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• pp.324-335
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• 1979

During the period of 4 years from August 1975 to August 1979 one hundred and forty seven cases of lung cancer were seen at Paik Foundation Hospital in Seoul, Korea. Among these 147 cases, 104 patients had primary carcinoma of the lung and the remainder was metastatic carcinoma to the lung. Among these 104 primary carcinoma patients, 73 cases were proven histologically as primary carcinoma of the lung. There were three cases of alveolar cell carcinoma [Table 1 ]. This clinical observation is based on those 73 cases including three case reports of the alveolar cell carcinoma. 1. Peak incidence was observed in the 5th decade of life. Male to female ratio was 2 to 1 [Fig. 1]. 2. Pathological classifications were as follows: epidermoid carcinoma, 24 cases [32.9%]; undifferentiated carcinoma, 20 cases [27.4%]; adenocarcinoma, 15 cases [20.5%]; bronchioloalveolar carcinoma [5.5%] and positive cytology, 10 cases [13.7%] [Fig. 2]. 3. Evidence of inoperability was observed in 55 patients [75% of the 73 cases] [Table 3]. 4. Among those 73 cases, operability was evaluated in 18 patients or 25%. One patient refused operation and 17 patients [23.6%] were explored. In 11 [15%] out of 17 patients, thoracotomies were performed. Six cases were pneumonectomies and 5 cases were lobectomies or bilobectomies [Fig. 3]. 5. First case of alveolar cell carcinoma was a 46 year-old housewife complaining of cough and hemoptysis for one year. The plain chest X-ray and bronchogram showed characteristic pictures as Figures 4 and 5. A pneumonectomy was carried out. Histologically, a beautiful alveolar carcinoma consisted of the characteristic tall columnar epithelial cells, which were lining the alveolar spaces as seen in Figures 6, 7, 8, and 20. 6. In the second case of 41 year old male, predominant clinical feature was single, well defined mass in the right lower lobe [Fig. 10 and 11] on chest X-ray. Bilobectomized specimen showed fragile, soft and hard tissue containing mucoid secretions and focal yellowish necrosis with pigmentation on cut surface [Fig. 12]. Slides showed tumor cells lined up along the alveolar septa with papillary projections [Fig. 13 and 14]. 7. Third case of alveolar cell carcinoma was a 50-year-old housewife with hemoptysis. An outstanding clinical picture was a round to lobulated mass in the right upper lobe [Fig. 16]. She is living now, 2 years and 1 month post-operatively, but has arrived at terminal stage with military nodular disseminations to the contralateral lung [Fig. 19].

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

• Korean Journal of Head & Neck Oncology
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• v.34 no.2
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• pp.23-28
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• 2018

Background/Objectives: Adenoid cystic carcinoma is the second most common salivary carcinoma. It occurs commonly in the submandibular gland, sublingual gland and minor salivary gland. Local recurrence and distant metastasis are the leading cause of death. The aim of this study was to evaluate long-term oncologic outcomes of patients with head and neck adenoid cystic carcinoma focusing on distant metastasis. Materials & Methods: We retrospectively studied 39 patients who were diagnosed with and treated for adenoid cystic carcinoma of the head and neck from December 1996 to May 2018. The clinicopathologic characteristics of patients such as age, sex, primary site and TNM stage, and treatment methods, recurrence and distant metastasis after treatment, survival rate, and treatment method for recurrence were analyzed. Results: Of 39 patients, 18 were males and 21 were females, and the mean age was $5.9{\pm}14.4$ (28-89) years. The most common primary site was oral cavity (12 cases), and followed by sino-nasal cavity (11 cases), parotid gland (5 cases), and etc. For treatment, 17 patients underwent surgery alone, 16 received surgery with postoperative radiation therapy, and 3 patients received radiation therapy only. Three patients refused any further treatments. Recurrence occurred in 15 patients. The most common site of recurrence was the lung. The mean time to recurrence was 31.7 months. The 5 and 10 years' overall survival rate was 79.3% and 74%, respectively. The 2 and 5 years' overall survival rate was 69.6% and 62.6% in patients with distant metastasis. Conclusion: Distant metastasis is an important prognostic factor in adenoid cystic carcinoma, and eventually one third of patients have distant metastasis, especially in the lung. An appropriate treatment for lung metastasis is necessary because some patients with pulmonary metastasis survive for a quite long time.

• Tuberculosis and Respiratory Diseases
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• v.73 no.6
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• pp.303-311
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• 2012

Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.78-83
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• 2008

Purpose : Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Although survival rate of osteosarcoma patients has markedly improved, about 20-30% of patients still have a relapse. This study was aimed to find factors that influence postrelapse survival of osteosarcoma in childhood and adolescents. Methods : Between 1985 and 2004, of 461 patients who were diagnosed and treated as osteosarcoma in Korean Cancer Center Hospital, 180 patients with recurrent osteosarcoma were retrospectively reviewed. We examined survival rates and analyzed prognostic factors, such as relapse site, post-relapse treatment methods, pathologic response to neoadjuvnat chemotherapy, metastasis at first diagnosis, and relapse free interval. Results : The overall recurrence rate of patients with osteosarcoma was 39%. The 5-year and 10-year postrelapse survival rates in the recurrent osteosarcoma were 13% and 4%, respectively. The 5-year post-relapse survival rate was influenced by site of relapse (lung, 39%; local, 0%; lung & bone, 25%; others, 12%; P<0.05), relapse-free interval (<12 months, 13%; ${\geq}12$ months, 44%, P<0.05), and post-relapse treatment methods (with surgery, 38%; without surgery, 11%; P<0.05). Conclusion : The survival rate of recurrent case is very low after 10 years, so new second-line chemotherapy and active treatment is needed to increase survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy could either cure patients with recurrent osteosarcoma or significantly prolong their survival.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3029-3034
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• 2015

Background: While the perinatal outcomes of active maternal smoking are well documented, results of the effects of environmental tobacco smoke (ETS) exposure during pregnancy are inconsistent. We aimed to examine the effect of ETS exposure, assessed by maternal hair nicotine levels at $35^{th}$ week of gestation, on birth weight and the risk of small for gestational age (SGA) and low birth weight (LBW). Materials and Methods: A total of 871 non-smoking healthy pregnant women were recruited by one Korean hospital between 1 October 2006 and 31 July 2007. Hair samples were collected and anthropometric questionnaires administered at $35^{th}$ week of gestation. The primary outcome was birth weight and secondary outcomes were the risk of babies being SGA and LBW. Results: Log-transformed hair nicotine concentrations were inversely related with birth weight after adjusting for confounding variables (${\beta}=-0.077$, p=0.037). After stratifying hair nicotine levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342g (T1) 3,296g (T2) and 3,290 g (T3), respectively. However the difference between groups was not statistically significant by analysis of co-variance (ANCOVA) adjusting for covariates (p=0.062). In logistic regression analysis, the risk of SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group (T1), after controlling for confounding variables. The risk of low birth weight (<2,500g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the risk of babies being below 3,000g birth weight was increased in the T3 group (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. Conclusions: Maternal ETS exposure during pregnancy was inversely related with birth weight. The risk of SGA increased in the highest ETS exposure group compared with in the low exposure group. To prevent ETS exposure during pregnancy, more comprehensive tobacco control policies are needed.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.252-259
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• 2005

To clarify the clinicopathologic features of small-cell carcinomas (SCC) of the stomach, we reviewed three cases of surgically treated SCC. The first case was a pure SCC, with severe pancreatic invasion and peritoneal seeding. A gastro-jejunostomy was performed. Postoperative chemotherapy was performed with CDDP and VP-16 (8 cycles) but showed disease progression (PD); a consecutive chemotherapy with CDDP and irinotencan (2 cycles) also showed PD. A third line with CDDP, VP16, ifosfamide, and mesna was followed by a 4th line (CDDP and Taxol). The male patient died with liver metastasis and peritoneal seeding 14 months after the operation. The second case was a SCC mixed with a poorly differentiated adenocarcinoma. Profound lymphadenopathy and liver metastasis were found. Two cycles of preoperative chemotherapy with TS-1 and CDDP were performed, which showed nearly complete remission for lymphadenopathy and partial response for the primary tumor site and liver metastatic lesion. A total gastrectomy and extended lymphadenectomy was performed. There were no viable cancer cells in 35 retrieved lymph nodes. Postoperative chemotherapy using the same regimen was performed for 4 cycles. Enlarged liver metastasis was found at the follow-up CT scan, so a posterior segmentectomy of liver was performed. After liver surgery, the chemotherapy regimen was changed to irinotecan and cisplatin. This male patient has been in good health for the f4 months since gastric surgery. The third case was a pure SCC, and a subtotal gastrectomy was performed curatively. That male patient received 5 cycles of TS-1 and is still in good health 14 months after operation.