• 대한두개안면성형외과학회지
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• 제20권4호
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• pp.239-245
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• 2019

Background: Lidocaine spray is a local anesthetic that improves random-pattern skin flap survival. The fractional ablative carbon dioxide laser (FxCL) produces vertical microchannels that delivers topically applied drugs to the skin. In this study, we hypothesized that FxCL therapy would enhance the lidocaine effect to improve random-pattern skin flap survival in rats. Methods: McFarlane random-pattern skin flaps were elevated in 48 rats, which were divided into four groups according to treatment: FxCL+lidocaine, FxCL, lidocaine, and nontreatment (control). On postoperative day 7, necrotic flap areas, the number of capillary vessels, and neutrophil count were evaluated. Anti-rat vascular endothelial growth factor (VEGF) and CD31 antibody activity were also evaluated by immunohistochemical staining. Results: Flap survival rate was $53.41%{\pm}5.43%$, $58.16%{\pm}4.80%$, $57.08%{\pm}5.91%$, and $69.08%{\pm}3.20%$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Mean neutrophil count in the intermediate zone excluding the necrotic tissue was $41.70{\pm}8.40$, $35.43{\pm}6.41$, $37.23{\pm}7.15$, and $27.20{\pm}4.24cells/field$ in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Anti-rat VEGF and CD31 antibody activity were the highest in the FxCL+lidocaine group. Conclusion: FxCL with lidocaine had a positive effect on random-pattern skin flap survival in rats. Thus, FxCL with lidocaine spray should be considered as a new treatment option to improve flap viability.

• 대한두경부종양학회지
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• 제38권1호
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• pp.17-24
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• 2022

Background/Objectives: This study analyzed the prognostic significance of clinico-pathologic factors including comprehensive nodal factors in parotid gland cancers (PGCs) patients and constructed a survival prediction model for PGCs patients using machine learning techniques. Materials & Methods: A total of 131 PGCs patients were enrolled in the study. Results: There were 19 cases (14.5%) of lymph nodes (LNs) at the lower neck level and 43 cases (32.8%) involved multiple level LNs metastases. There were 2 cases (1.5%) of metastases to the contralateral LNs. Intraparotid LNs metastasis was observed in 6 cases (4.6%) and extranodal extension (ENE) findings were observed in 35 cases (26.7%). Lymphovascular invasion (LVI) and perineural invasion findings were observed in 42 cases (32.1%) and 49 cases (37.4%), respectively. Machine learning prediction models were constructed using clinico-pathologic factors including comprehensive nodal factors and Decision Tree and Stacking model showed the highest accuracy at 74% and 70% for predicting patient's survival. Conclusion: Lower level LNs metastasis and LNR have important prognostic significance for predicting disease recurrence and survival in PGCs patients. These two factors were used as important features for constructing machine learning prediction model. Our machine learning model could predict PGCs patient's survival with a considerable level of accuracy.

• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• Journal of Gastric Cancer
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• 제23권4호
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• pp.598-608
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• 2023

Purpose: Lymph node (LN) metastasis is a crucial factor in the prognosis of patients with gastric cancer (GC) and is known to occur more frequently in cases with an advanced T stage. This study aimed to analyze the survival data of patients with advanced LN metastasis in T1 GC. Materials and Methods: From January 2008 to June 2018, 677 patients with pathological stage II GC who underwent radical gastrectomy were divided into an early GC group (EG: T1N2 and T1N3a, n=103) and an advanced GC (AGC) group (AG: T2N1, T2N2, T3N0, T3N1, and T4aN0, n=574). Short- and long-term survival rates were compared between the 2 groups. Results: A total of 80.6% (n=83) of the patients in the EG group and 52.8% (n=303) in the AG group had stage IIA AGC. The extent of LN dissection, number of retrieved LNs, and short-term morbidity and mortality rates did not differ between the 2 groups. The 5-year relapse-free survival (RFS) of all patients was 87.8% and the overall survival was 84.0%. RFS was lower in the EG group than in the AG group (82.2% vs. 88.7%, P=0.047). This difference was more pronounced among patients with stage IIA (82.4% vs. 92.9%, P=0.003). Conclusions: T1 GC with multiple LN metastases seems to have a worse prognosis compared to tumors with higher T-stages at the same level. Adjuvant chemotherapy is highly recommended for these patients, and future staging systems may require upstaging T1N2-stage tumors.

• Journal of Hospice and Palliative Care
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• 제11권4호
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• pp.181-187
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• 2008

목적: 말기 암 환자에게 있어서 정확한 여명 예측은 환자의 효율적인 치료 계획을 세우고 환자의 삶의 질을 높이는데 있어서 중요하다. 본 연구에서는 말기 암 환자에서 호중구-림프구 비가 생존기간 예측을 위한 예후 인자로서 유용한가를 알아보고자 한다. 방법: 2004년 1월부터 2007년 6월까지 말기 암 환자로 완화 치료를 목적으로 영동세브란스병원 가정의학과에 입원 혹은 전입되어 치료를 받는 중 사망한 67명의 환자를 대상으로 하였다. 호중구-림프구 비에 따라서 3개의 군으로 나누어 과거 병력, 신체 계측, 임상 증상, 혈액검사 소견, 생존기간을 분석하였다. 결과: 호중구-림프구 비가 가장 높은 군(${\geq}12.5$)에서 환자의 생존기간이 단변량 분석에서 통계적으로 유의하게 짧았으며(hazard ratio (HR)=3.270, P=0.001)), 저하된 활동도, 호흡 곤란 증상을 보정한 다변량 분석에서도 통계적 유의성을 보였다(HR=2.907, P=0.007). 완화 치료를 위해 입원 혹은 전입된 시점에 비하여 사망이 임박한 시점에서 호중구-림프구 비는 의미 있는 증가를 보였다(P=0.001). 결론: 호중구-림프구 비는 말기 암환자에서 생존기간 예측을 위한 독립적인 예후 인자로 확인 되었다.

• Radiation Oncology Journal
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• 제33권2호
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• pp.75-82
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• 2015

Purpose: We evaluated the prognostic significance of T3 subtypes and the role of adjuvant radiotherapy in patients with resected the American Joint Committee on Cancer stage IIB T3N0M0 non-small cell lung cancer (NSCLC). Materials and Methods: T3N0 NSCLC patients who underwent resection from January 1990 to October 2009 (n = 102) were enrolled and categorized into 6 subgroups according to the extent of invasion: parietal pleura chest wall invasion, mediastinal pleural invasion, diaphragm invasion, separated tumor nodules in the same lobe, endobronchial tumor <2 cm distal to the carina, and tumor-associated collapse. Results: The median overall survival (OS) and disease-free survival (DFS) were 55.3 months and 51.2 months, respectively. In postoperative T3N0M0 patients, the tumor size was a significant prognostic factor for survival (OS, p = 0.035 and DFS, p = 0.035, respectively). Patients with endobronchial tumors within 2 cm of the carina also showed better OS and DFS than those in the other T3 subtypes (p = 0.018 and p = 0.016, respectively). However, adjuvant radiotherapy did not cause any improvement in survival (OS, p = 0.518 and DFS, p = 0.463, respectively). Only patients with mediastinal pleural invasion (n = 25) demonstrated improved OS and DFS after adjuvant radiotherapy (n = 18) (p = 0.012 and p = 0.040, respectively). Conclusion: The T3N0 NSCLC subtype that showed the most favorable prognosis is the one with endobronchial tumors within 2 cm of the carina. Adjuvant radiotherapy is not effective in improving survival outcome in resected T3N0 NSCLC.

• Journal of Chest Surgery
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• 제39권5호
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• pp.376-381
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• 2006

배경: Ki-67 단백질은 세포의 증식활성도를 나타내는 생물표식자로, 비소세포폐암 환자에서 Ki-67 단백질의 증가는 예후에 나쁜 영향을 미치는 것으로 알려져 있다. 이 연구는 비소세포폐암으로 폐절제술을 실시한 환자에서 Ki-67 단백질의 발현정도를 조사하여, 단백질의 발현증가가 환자의 임상적 병리적 양상과 술 후 재발과 생존기간에 미치는 영향을 알아보기 위해 시행되었다. 대상 및 방법: 근치적 폐절제술을 실시한 38명의 비소세포폐암 조직에서 단클론항체 Ki-67로 면역조직화학염색을 실시하여 Ki-67 Labeling Index (LI)를 구하였다. 환자를 Ki-67 증가군$(LI{\ge}20%)$과 Ki-67 비증가군(LI<20%)으로 분류하여, 두 군의 술 전 임상적 병리적 특성, 술 후 생존기간 및 무병생존기간을 비교하였다. 결과: Ki-67 LI는 불균질한 분포를 보였고 평균 LI는 $20.0{\pm}20.1%$였다. Ki-67 증가군과 비증가군 간에나이, 성별, 흡연, TNM 병기, 혈관침윤은 유의한 차이가 없었다. 그러나 증가군은 비증가군에 비해 편평상피암이 많고, 분화도가 나쁘며, 임파침윤이 많았다$(p{\le}0.05)$. 증가군은 중앙 생존기간(47.2 vs. 96.5개월)과 중앙 무병생존기간(18.2 vs. 72.3개월)이 비증가군보다 짧았으나 통계적 유의성은 없었다(각각 p=0.312, p=0.327). 결론: 이상의 연구를 통해 비소세로폐암 환자에서의 Ki-67 단백질 발현증가는 수술 후 환자의 예후에 나쁜 인자로 작용하여 생존기간과 무병생존기간이 짧아지는 경향을 보였으나 통계적 유의성이 부족하여 향후 지속적인 연구가 필요할 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3299-3304
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• 2014

Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1759-1767
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• 2016

Background: Uterine sarcoma is a group of rare gynecologic tumors with various natures, and different lines of treatment. Most have a poor treatment outcome. This study targeted clinical characteristics, treatment, overall survival (OS), progression-free survival (PFS), and prognostic factors in uterine sarcoma patients in one tertiary center for cancer care. Materials and Methods: Uterine sarcoma patients who were treated at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital between January 1994 and December 2014 were identified. Clinico-pathological data were analyzed. Prognostic outcomes were examined by Kaplan-Meier curves and Cox regression analysis. Results: We identified 46 uterine sarcoma patients: 25 carcinosarcoma (CS) (54.3%), 15 leiomyosarcoma (LMS) (32.6%), and 6 undifferentiated uterine sarcoma (UUS) (13.1%) cases. Mean age was $54.0{\pm}11.9years$ (range 25-82 years). Abnormal uterine bleeding was the most common presenting symptom (63.0%). Among 33 patients (71.7%) who had pre-operative tissue collected, diagnosis of malignancy was correct in 29 (87.9%). All patients received primary surgery and retroperitoneal lymph nodes were resected in 34 (73.9%). After surgery, 5 (10.9%) had gross residual tumors. Stage I disease was most commonly found (56.5%). Adjuvant treatment was given to 27 (58.7%), most commonly chemotherapy. After a median follow-up of 16.0 months (range 0.8-187.4 months), recurrence was encountered in 22 patients (47.8%). Median time to recurrence was 5.8 months (range1.0-105.5 months). Distant metastasis was more common than local or locoregional failure. The 2-year PFS was 45.2% (95% confidence interval [CI], 30.6%-59.7%) and the 2-year OS was 48.3% (95% CI, 33.3%-60.7%). Multivariable analyses found residual disease after surgery as a significant factor only for PFS. Conclusions: Uterine sarcoma is a rare tumor entity. Even with multimodalities of treatment, the prognosis is still poor. Successful cytoreductive surgery is a key factor for a good survival outcome.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2101-2107
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• 2012

Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.