• Korean Journal of Bronchoesophagology
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• v.15 no.2
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• pp.49-56
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• 2009

Purpose : To evaluate the treatment outcome for patients with locally advanced, unresectable esophageal cancer treated with relatively high dose radiation therapy(RT). Materials and Methods : From January 2000 to December 2008, 32 patients with locally advanced unresectable or medically inoperable esophageal cancer were treated with radiation therapy(RT) with or without concurrent chemotherapy. Ten patients were excluded from analysis because of distant metastasis and drop off. Patient distributions according to AJCC stages II, III IVa were 7(31.8%), 12(54.6%), 3(13.6%) respectively. The locations of tumor were cervical/upper thorax 3 (13.6%), mid thorax 13(59.1%), and lower thorax/abdominal 6(27.3%), respectively. Eleven patients received RT only, and 11 patients received cisplatin based concurrent chemoradiotherapy(CCRT). Median radiation dose was 65 Gy(range 57.6~72 Gy). Results : The median follow-up was 9.1 months(range 1.9~43.8 months). The response rates for complete response, Partial response, stable disease and Persistent disease were 6(27.3%), 11(50.0%), 4(18.2%) and 1(4.5%), respectively. Two patients(9.1%) suffered from esophageal stenosis and stents were inserted. Two patients(9.1%) had Grade 3 radiation pneumonitis and one of them expired due to acute respiratory distress syndrome(ARDS) at 36 days after completion of radiation therapy. The recurrence rate was 11(50.0%). The patterns of recurrence were persistent disease and local progression in 5(22.7%), local recurrence 3(13.7%) and concomitant local and distant recurrence in 3(13.7%). The overall survival(OS) rate was 32.1% at 2 years and 21.4% at 3 years(median 12.0 months). Disease free survival(DFS) rate was 17.3% at 2 and 3 years. All patients who had no dysphagia at diagnosis showed complete response after treatment and 100% OS at 3 years(p=0.0041). The OS for above 64.8 Gy group and 64.8 Gy or below group at 3 years were 60.6% and 9.1%(p=0.1341). The response to treatment was the only significant factor affecting OS(p=0.004). Conclusion : Relatively high dose radiation therapy in unresectable esophageal cancer tended to have a better outcome without increased complication rate. Further study with more patients is warranted to justify improved result.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1255-1258
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• 2015

Background: Locally advanced head and neck cancer is generally incurable and has a short survival rate. This study aimed to evaluate symptom relief, disease response, and acute toxicity after palliative hypo-fractionated radiotherapy and long-term survival in affected patients. Materials and Methods: Between January 2011 to December 2011, 80 patients who were histopathologically diagnosed as having stage III or stage IV head and neck squamous cell carcinoma based on Eastern Cooperative Oncology Group (ECOG) performance status 1-3, were offered palliative radiotherapy (20 Gy/5Fr/5 Days). Later these patients were evaluated on 30th day after completion of treatment for disease response based on World Health Organisation (WHO) criteria and palliation of symptoms using symptomatic response grading and acute toxicities by the Radiation Therapy Oncology Group (RTOG). Many patients were given post radiation therapy (RT) palliative chemotherapy for appropriate palliative care and a few patients were selected for further curative RT. The overall survival was also evaluated among this group of patients with last follow up date of 1st May, 2014. Results: The most common presenting complaint was pain followed by dysphagia. Most patients (60-70%) had appreciable relief in their presenting symptoms. A good response was observed in the majority following palliative RT; a few patients had progressive disease and some had stable and regressed disease. None of the patients experienced radiation toxicity that required hospital admission. Almost all showed grade one and two acute skin and mucosal toxicity one month after completion of treatment. The mean survival days for patients given only hypofractionated palliative RT was 307 days, those with post palliative RT and palliative chemotherapy was 390 days and patients who went on to receive further palliative RT and curative RT dose had significantly overall survival of 582 days. Conclusions: Advanced head and neck cancer should be identified for suitable palliative hypofractionated radiotherapy to achieve acceptable symptom relief in a great proportion of patients and should be followed by palliative chemotherapy or curative RT in suitable cases for long-term symptom-free survival.

• Clinical and Experimental Pediatrics
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• v.56 no.9
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• pp.401-406
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• 2013

Purpose: We performed a pilot study to determine the benefit of high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) for patients with Ewing sarcoma family of tumors. Methods: We retrospectively analyzed the data of patients who received HDCT/autoPBSCT at Korea Cancer Center Hospital. Patients with relapsed, metastatic, or centrally located tumors were eligible for the study. Results: A total of 9 patients (3 male, 6 female), with a median age at HDCT/autoPBSCT of 13.4 years (range, 7.1 to 28.2 years), were included in this study. Patients underwent conventional chemotherapy and local control either by surgery or radiation therapy, and had achieved complete response (CR, n=7), partial response (n=1), or stable disease (n=1) prior to HDCT/autoPBSCT. There was no transplant-related mortality. However, the median duration of overall survival and event-free survival after HDCT/autoPBSCT were 13.3 months (range, 5.3 to 44.5 months) and 6.2 months (range, 2.1 to 44.5 months), respectively. At present, 4 patients are alive and 5 patients who experienced adverse events (2 metastasis, 2 local recur, and 1 progressive disease) survived for a median time of 2.8 months (range, 0.1 to 10.7 months). The 2-year survival after HDCT/autoPBSCT was $44.4%{\pm}16.6%$ and disease status at the time of HDCT/autoPBSCT tended to influence survival ($57.1%{\pm}18.7%$ of cases with CR vs. 0% of cases with non-CR, P=0.07). Conclusion: Disease status at HDCT/autoPBSCT tended to influence survival. Further studies are necessary to define the role of HDCT/autoPBSCT and to identify subgroup of patients who might benefit from this investigational treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10967-10970
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• 2015

Objective: To analyze the efficacy and survival associated factors of gefitinib combined with cisplatin and gemcitabine for advanced non-small cell lung cancer. Materials and Methods: A total of 57 patients with advanced non-small cell lung cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1 cycle, were treated with gefitinib combined with cisplatin and gemcitabine until disease progression. Efficacy, survival time and adverse reactions were observed. The Kaplan-Meier method was adopted for analysis of survival and Cox regression for associated influencing factors. Results: The patients were followed up until October 31, 2013, and the median follow-up time was 19 months. Of 57 patients, there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease progression. The remission rate was 21.1% and the disease control rate was 75.4%. The median progression-free survival (PFS) time and the median overall survival time were 10 months and 15.2 months. The one-year, two-year and three-year survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor pathological type and early efficacy were independent factors for the prognosis (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and diarrhea and slightly increasing level of aminopherase. The skin adverse event incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn in 31.6% (18/57). Conclusions: Gefitinib combined with cisplatin andgemcitabine, is effective for patients with IIIb~IV NSCLC who received multiple cycles of chemotherapy.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.374-383
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• 2017

Purpose: Bleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC. Materials and Methods: This study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated. Results: Successful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ${\geq}5$ units of RBCs was a significant risk factor for rebleeding. Conclusions: Despite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (${\geq}5$ units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.

• Tuberculosis and Respiratory Diseases
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• v.61 no.6
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• pp.533-546
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• 2006

Background: The aim of this study was to determine the effectiveness of self-efficacy promoting pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). Methods: thirty six patients, with clinically stable COPD were randomly assigned: 18 to a rehabilitation group and another 18 as a control group, The subjects participated in a the self-efficacy promoting pulmonary rehabilitation program for 8 weeks. This program consisted of education, breathing retraining, exercise training, relaxation and counseling. The control group received education only. The outcome variables were self-efficacy, dyspnea, exercise endurance, pulmonary function, and quality of life. Dyspnea was measured using the modified Borg scale. Exercise endurance was measured by the six minute walking distance. The quality of life was measured by the quality of life index for pulmonary disease patients. Results: In the rehabilitation group after performing the self-efficacy promoting pulmonary rehabilitation program, the self-efficacy score, exercise endurance, and quality of life score were higher than the control group (p=0.007, p=0.038, and p=0.039, respectively). and the exertional dyspnea score was significantly lower than controls(p=0.045). However, the dyspnea score and FEV1 were similar after performing the self-efficacy promoting pulmonary rehabilitation program. Conclusion: The self-efficacy promoting pulmonary rehabilitation program is effective to in improve self-efficacy, exertional dyspnea, exercise endurance and quality of life in patients with COPD.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.48.1-48.11
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• 2020

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39⁺ cells among CD8⁺ T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39⁺CD8⁺ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.

• Molecules and Cells
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• v.37 no.10
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• pp.734-741
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• 2014

Histone modifications on major transcription factor target genes are one of the major regulatory mechanisms controlling adipogenesis. Plant homeodomain finger 2 (PHF2) is a Jumonji domain-containing protein and is known to demethylate the histone H3K9, a repressive gene marker. To better understand the function of PHF2 in adipocyte differentiation, we constructed stable PHF2 knock-down cells by using the mouse pre-adipocyte cell line 3T3-L1. When induced with adipogenic media, PHF2 knock-down cells showed reduced lipid accumulation compared to control cells. Differential expression using a cDNA microarray revealed significant reduction of metabolic pathway genes in the PHF2 knock-down cell line after differentiation. The reduced expression of major transcription factors and adipokines was confirmed with reverse transcription- quantitative polymerase chain reaction and Western blotting. We further performed co-immunoprecipitation analysis of PHF2 with four major adipogenic transcription factors, and we found that CCATT/enhancer binding protein (C/EBP)${\alpha}$ and C/EBP${\delta}$ physically interact with PHF2. In addition, PHF2 binding to target gene promoters was confirmed with a chromatin immunoprecipitation experiment. Finally, histone H3K9 methylation markers on the PHF2-binding sequences were increased in PHF2 knock-down cells after differentiation. Together, these results demonstrate that PHF2 histone demethylase controls adipogenic gene expression during differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2401-2406
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• 2013

From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4827-4834
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• 2012

Tumor suppressor genes have received much attention for their roles in the development of human malignancies. Gelsolin has been found to be down-regulated in several types of human cancers, including leukemias. It is, however, expressed in macrophages, which are the final differentiation derivatives for the monocytic myeloid lineage, implicating this protein in the differentiation process of such cells. In order to investigate the role of gelsolin in leukaemic cell differentiation, stable clones over-expressing ectopic gelsolin, and a control clone were established from U937 leukaemia cells. Unlike the control cells, both gelsolin-overexpressing clones displayed retarded growth, improved monocytic morphology, increased NADPH and NSE activities, and enhanced surface expression of the ${\beta}$-integrin receptor, CD11b, when compared with the parental U937 cells. Interestingly, RT-PCR and western blot analysis also revealed that gelsolin enhanced p21CIP1 mRNA and protein expression in the overexpressing clones. Moreover, transient transfection with siRNA silencing P21CIP1, but not the control siRNA, resulted in a reduction in monocytic differentiation, accompanied by an increase in proliferation. In conclusion, our work demonstrates that gelsolin, by itself, is capable of inducing monocytic differentiation in U937 leukaemia cells, most probably through p21CIP1 activation.