• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.297-304
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• 2016

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.

• Journal of Korean Neurosurgical Society
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• 제58권2호
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• pp.93-100
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• 2015

Objective : Optimal treatment decision and estimation of the prognosis in traumatic brain injury (TBI) is currently based on demographic and clinical predictors. But sometimes, there are limitations in these factors. In this study, we analyzed three central nervous system biomarkers in TBI patients, will discuss the roles and clinical applications of biomarkers in TBI. Methods : From July on 2013 to August on 2014, a total of 45 patients were included. The serum was obtained at the time of hospital admission, and biomarkers were extracted with centrifugal process. It was analyzed for the level of S-100 beta (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1). Results : This study included 33 males and 12 females with a mean age of 58.5 (19-84) years. TBI patients were classified into two groups. Group A was severe TBI with Glasgow Coma Scale (GCS) score 3-5 and Group B was mild TBI with GCS score 13-15. The median serum concentration of S100B, GFAP, and UCH-L1 in severe TBI were raised 5.1 fold, 5.5 fold, and 439.1 fold compared to mild injury, respectively. The serum levels of these markers correlated significantly with the injury severity and clinical outcome (p<0.001). Increased level of markers was strongly predicted poor outcomes. Conclusion : S100B, GFAP, and UCH-L1 serum level of were significantly increased in TBI according to severity and associated clinical outcomes. Biomarkers have potential utility as diagnostic, prognostic, and therapeutic adjuncts in the setting of TBI.

• Journal of Korean Neurosurgical Society
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• 제52권2호
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• pp.92-97
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• 2012

Objective : This study was performed to determine the safety and outcome of concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide for Korean patients with a newly diagnosed glioblastoma. Methods : Patients were recruited from four institutions between 2004 and 2007. The patients received fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks and daily temozolomide, followed by 6 cycles of adjuvant temozolomide. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response, and safety. Results : A total of 103 patients were enrolled in this study. Ninety-six patients (93%) completed the CCRT and 54 patients (52%) received 6 cycles of adjuvant temozolomide. The response rate was 73% (53/73) and the tumor control rate was 92% (67/73). Of the 96 patients who completed the CCRT, the median OS was 18.0 months and the 1- and 2-year OS rates were 74 and 38%, respectively. The median PFS was 10.0 months and the 1- and 2-year PFS rates were 33 and 16%, respectively. The only significant prognostic factor of survival was the extent of surgical resection (p<0.05). CCRT resulted in grade 3 or 4 hematologic toxic effects in 8% of patients. No opportunistic infections were noted. Conclusion : This study is the first prospective multi-institutional report of CCRT and adjuvant chemotherapy with temozolomide for patients with a newly diagnosed glioblastoma in Korea. The current protocol may prolong the survival of Korean patients with a glioblastoma and may be tolerable in terms of toxicity.

• Radiation Oncology Journal
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• 제33권1호
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• pp.29-35
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• 2015

Purpose: To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. Materials and Methods: We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). Results: The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. Conclusion: The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

• Advances in pediatric surgery
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• 제10권2호
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• pp.136-141
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• 2004

1988년 9월부터 1999년 4월까지 가톨릭 대학교 의과대학 부속병원 외과에서 황달, 무담즙성 변 및 복부 종괴를 주소로 내원하여 간 외 담관낭이 동반된 담도폐쇄증으로 진단받은 7예의 환자의 임상상을 검토하였다. 전체 선천성 담도폐쇄증 환아 중 9.6 %에서 간 외 담관낭을 동반한 III 형의 담도폐쇄증을 보였다. 남여 성비는 2:5로 여아에서 높았다. 모두 카사이 수술을 시행하였으며 수술 시 평균연령은 57일이었다. 7예 중 3예 (42.9 %)에서 긴 생존기간을 보였다. 예후에 미치는 인자에 대해서는 지속적인 연구관찰이 필요할 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• 제57권6호
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• pp.264-270
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• 2014

Purpose: Acute necrotizing encephalopathy (ANE) is a fulminant disease of the brain characterized by bilateral thalamic lesions, and is prevalent among children in East Asia. The prognosis of ANE is usually poor with a high mortality rate and neurological sequelae. This study aimed to delineate the clinical characteristics and prognostic factors of ANE. Methods: We retrospectively analyzed clinical data of 399 pediatric patients with encephalitis who were admitted to Samsung Medical Center from December 1998 to March 2011. We enrolled ten patients (11 cases) with ANE and analyzed their demographic, clinical, and neuroimaging data. The location and extent of the brain regions were checked based on fluid-attenuated inversion recovery, T1-, and T2-weighted imaging findings; the presence of contrast enhancement, restricted diffusion, and hemorrhage. Results: Ten patients were identified, including one patient with two episodes. The median age of onset was 1.5 years (0.4-8.4 years). The mortality rate was 40%, and only 30% of patients survived without neurological sequelae. The definite involvement of the brainstem on brain magnetic resonance imaging was significantly correlated with mortality (P =0.04). Conclusion: Broad and extensive brainstem involvement suggested the fulminant course of ANE. Early diagnosis of ANE before brainstem involvement, through careful identification of symptoms of brain dysfunction, may be the best way to achieve better neurological outcomes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4077-4080
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• 2015

The chemokine receptor 4 (CXCR4) has been widely used in diagnosis and prognosis of colorectal cancer (CRC). However, there is no current consensus on the impact of CXCR4 on CRC patients. The purpose of this study was to evaluate the prognostic and clinicopathological importance of CXCR4 in CRC patients. Databases, such as PubMed, Cochrane library, CBM and EMBASE updated to 2014 were searched to include eligible articles. We analysed correlations between CXCR4 expression and clinicopathological features and overall survival (OS). A total of 1, 055 CRC patients from twelve studies were included in the study. The pooled odds ratios (ORs) which indicated CXCR4 expression was likely to be associated with TNM stage (OR=0.43, CI=0.34-0.55, P<0.00001), lymph node status (OR=2.23, CI=1.23-4.05, P=0.008) and vascular invasion (OR=2.21, CI=1.11-4.39, P=0.02). Poor overall survival of CRC cancer was found to be significantly related to CXCR4 overexpression (hazard ratio (HR) 1.36 CI=1.17-1.59, P<0.0001), whereas combined ORs revealed that CXCR4 expression had no correlation with gender or differentiation. Based on the published studies, CXCR4 overexpression in patients w ith CRC indicates poor survival outcome and clinicopathological factors.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6475-6479
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• 2012

Background: Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Materials and Methods: Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Results: Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. Conclusions: We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1539-1544
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• 2014

Purpose: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). Methods: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. Results: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. Conclusions: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1585-1588
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• 2014

Background: Data regarding childhood and adolescent non Hodgkin lymphomas in Iran are limited. The aim of this study was to assess the epidemiological and histomorphological features and survival of affected patients in our center. Materials and Methods: The clinicopathologic features and outcome of 44 children and adolescents with non Hodgkin lymphoma diagnosed during 2004-2012, were investigated retrospectively. The influence of potential prognostic parameters in overall survival was investigated by log-rank test and Cox regression analysis. Results: The mean age at presentation was $13.8{\pm}6.16$ years with a male predilection (M: F=3:1). Malignant lymphoma, not otherwise specified, diffuse large cell lymphoma and Burkitt lymphoma were the three most common histological types observed. The tumors were 36.4% intermediate grade, 27.3% high grade and 34.1% belonged to the malignant lymphoma not otherwise specified group. Immunohistochemistry findings were available in 39 cases. Out of these cases 33 (84.6%) had B cell lineage, 4 (10.25%) T cell lineage and 2 (5.12%) of the cases belonged to miscellaneous group. 3 year and 5 year survivals were 48% and 30% respectively and median survival was 36 months (95%CI=21.7-50.3 months). Overall survival in patients with high grade tumors was 19.5 months, in the intermediate group,79 months, and for malignant lymphomas not otherwise specified it was 33.6 months (p value=0.000). Conclusions: The survival rate for children and adolescents with non Hodgkin lymphomas at our center during 2004-2012 was at a low level.