• Journal of Korean Neurosurgical Society
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• v.63 no.6
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• pp.707-716
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• 2020

Objective : The function of B7H3, a member of the B7 family of proteins, in neuroblastoma (NB) remains poorly characterized. Here we examine the expression pattern of B7H3 in clinical NB specimens and characterize the phenotype of B7H3 knock-down in NB cell line. Methods : Immunohistochemical (IHC) staining was carried out to assess the expression of B7H3 in clinical NB specimens. Survival association was analyzed using five Gene Expression Omnibus (GEO) datasets (GSE85047, GSE45480, GSE62564, GSE16476, GSE49710). Clonogenic survival and flow cytometry were performed after B7H3 knockdown to assess the cellular proliferation and cell survival in vitro. Impact of B7H3 silencing on NB growth was examined in vivo using the SH-SY5Y xenograft model. Results : On IHC staining, B7H3 was widely expressed in clinical NB specimens. Analysis of the transcriptional profiles of five GEO datasets clinically annotated NB specimens revealed that decreased B7H3 expression was associated with improved overall survival. B7H3 knockdown suppressed the proliferation of the SH-SY5Y NB model in vitro and in vivo. Cell cycle analysis revealed that B7H3 silencing induced G1/S arrest. This arrest was associated with the suppression of E2F1 expression and induction of Rb expression. Conclusion : Our results demonstrate that B7H3 expression correlate with clinical survival in NB patients. Preliminary studies suggest that B7H3 may mediate the G1/S transition.

• Progress in Medical Physics
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• v.28 no.1
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• pp.11-15
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• 2017

Relative biological effectiveness (RBE) of particle beam needs to be evaluated at particle beam therapy centers before the clinical application of the particle beam. However, since RBE analysis is implemented manually, it is useful to have a tool that can easily and effectively handle the data of experiments to generate cell survival curve and to analyze RBE simultaneously. In this work, the development of a program for RBE analysis of particle beam therapy was presented. This RBE analysis program was developed to include two parts; fitting the cell survival curves to linear-quadratic model and calculating the RBE values at a certain endpoint using fitting results. This program was also developed to simultaneously compare and analyze the template results that stored experiment data with photon and particle beam irradiations. The results of the cell survival curve obtained by each irradiation can be analyzed by the user on a desired data after reading the template stored in the easy-to-use excel file. The analysis results include the cell survival curves with error range, which are appeared in the screen and the ${\alpha}$ and ${\beta}$ parameters of linear-quadratic model with 95% confidence intervals, RBE values, and $R^2$ values to evaluate goodness-of-fit of survival curves to model, which are stored in a text cvs file. This software can generate cell survival curve, fit to model, and calculate RBE all at once with raw experiment data, so it helps users to save time for data handling and to reduce the possibility of making error on analysis. As a coming plan, we will create a user-friendly graphical user interface to present the results more intuitively.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.443-448
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• 2004

Background : Small-cell carcinomas of lung have a tendency for rapid growth and early wide metastasis. Despite the high response rates of combination chemotherapy alone or with radiotherapy, the overall long-term survival rate is very disappointing. According to autopsy findings, the common cause of failure is local recurrence in the primary cancer site. Therefore, surgical resection with combined chemotherapy has recently been attempted for very early stage small-cell carcinomas of the lung. Methods : 10 patients (TNM I & II: 5 cases each) undergoing surgical resection for small-cell carcinomas of the lung were treated with adjuvant chemotherapy in an attempt to prolong survival. Of these, 9 patients received chemotherapy, and a retrospective study for survival undertaken (Kaplan-Meier analysis). Results : The median survival time was 26 months, and the 2- and 5-year survival rates were 68.6 and 46.7%, respectively. If the 1 patient not having undergone chemotherapy was excluded, the 2-, 5-year survival rates were 76.2 and 50.8%, respectively? No difference in the survival rate was seen between patients with TNM stages I and II. Conclusion : Adjuvant chemotherapy after surgical resection results in prolonged survival for patients with TNM stages I and II small-cell carcinomas of the lung.

• Journal of Chest Surgery
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• v.52 no.4
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• pp.195-204
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• 2019

Lobectomy is considered the standard strategy for early-stage non-small cell lung cancer (NSCLC). However, sublobar resection for NSCLC has recently received increased attention. The objective of this study was to compare 5-year survival, recurrence-free survival, postoperative mortality, and postoperative morbidities in patients who received segmentectomy versus those who received lobectomy through a meta-analysis. Sixteen studies were included and the combined hazard ratios or odds ratios were calculated. The results revealed that the 5-year survival rate after segmentectomy was comparable to that of lobectomy for stage IA NSCLC. However, segmentectomy for stage I NSCLC had lower rates of postoperative mortality and morbidities than lobectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.277-280
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• 2014

Background: Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population. Materials and Methods: A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance. Results: The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non-seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2). Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports.

• Korean Journal of Head & Neck Oncology
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• v.33 no.1
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• pp.15-19
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• 2017

Background/Objective: The survival and recurrence pattern of the patients with primary cancer of the external auditory canal was evaluated. Materials & Methods: Seventeen patients with primary cancer of the external auditory canal from 2002 to 2013 was analyzed retrospectively. Overall survival, recurrence free survival, local recurrence free survival and distant metastasis free survival was calculated by Kaplan-Meyer's method. Results: Five year overall survival rate, 5 year recurrence free survival rate, 5 year local recurrence free survival rate and 5 year distant metastasis free survival rate were 49.3% 54.9%, 64.7% and 69.6% respectively. The recurrence pattern is different to the pathologic type, squamous cell carcinoma or adenoid cystic carcinoma. The patients with squamous cell carcinoma showed local recurrence and the patients with adenoid cystic carcinoma showed distant metastasis mainly. Conclusion: Primary cancer of external auditory canal showed different clinical course depend on the pathologic diagnosis.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.19-26
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• 1995

Purpose : Surgery is the treatment of choice for resectable non-small cell lung cancer. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. A retrospective analysis of Patients with stage I non-samll cell lung cancer treated with curative radiation therapy was performed to determine the results of curative radiation therapy and patterns of failure, and to identify factors that may influence survival. Materials and Methods : From 1986 through 1993, 39 Patients with T2N0M0 non-small cell lung cancer were treated with curative radiation therapy at department of radiation oncology, Kyungpook national university hospital. All Patients were not candidates for surgical resection because of either Patient refusal (16 patients), poor pulmonary function (12 patients), old age (7 patients), Poor Performance (2 patients) or coexisting medical disease (2 patients). Median age of patients was 67 years. Histologic cell type was squamous cell carcinoma in 36, adenocarcinoma in 1, large cell carcinoma in 1 and mucoepidermoid carcinoma in 1. All patients were treated with megavoltage irradiation and radiation dose ranged from 5000cgy to 6150cGy with a median dose of 6000cGy. The median follow-up was 17 months with a range of 4 to 82 months, Survival was measured from the date therapy initiated. Results : The overall survival rate for entire Patients was $40.6\%$ at 2 years and $27.7\%$ at 3 years, with a median survival time of 21 months. The disease-free survival at 2 and 3 years was $51.7\%$ and $25.8\%$, respectively. Of evaluable 20 patients with complete response, 15 patients were considered to have failed. Of these, 13 patients showed local failure and 2 patients failed distantly. Response to treatment (p=0.0001), tumor size (p=0.0019) and age (p=0.0247) were favorably associated with overall survival. Only age was predictive for disease-free survival (p = 0.0452). Conclusion : Radiation therapy is an effective treatment for small (less than 3cm) tumors, and should be offered as an alternative to surgery in elderly or infirm patients. Since local failure is the prominent Patterns of relapse, potential methods to improve local control with radiation therapy are discussed.

• BMB Reports
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• v.34 no.6
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• pp.578-583
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• 2001

As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.464-473
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• 2018

Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.11
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• pp.1789-1800
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• 2019

Objective: Although alveolar macrophages play a key role in the respiratory immunity of livestock, studies on the mechanism of differentiation and survival of alveolar macrophages are lacking. Therefore, we undertook to investigate changes in the lipid metabolism and survival rate, using 3D4/31 macrophages and Dudleya brittonii which has been used as a traditional asthma treatment. Methods: 3D4/31 macrophages were used as the in vitro porcine alveolar macrophages model. The cells were activated by exposure to phorbol 12-myristate 13-acetate (PMA). Dudleya brittonii extraction was performed with distilled water. For evaluating the cell survival rate, we performed the water-soluble tetrazolium salt cell viability assay and growth curve analysis. To confirm cell death, cell cycle and intracellular reactive oxygen species (ROS) levels were measured using flow cytometric analysis by applying fluorescence dye dichlorofluorescein diacetate and propidium iodide. Furthermore, we also evaluated cellular lipid accumulation with oil red O staining, and fatty acid synthesis related genes expression levels using quantitative polymerase chain reaction (qPCR) with SYBR green dye. Glycolysis, fatty acid oxidation, and tricarboxylic acid (TCA) cycle related gene expression levels were measured using qPCR after exposure to Dudleya brittonii extract (DB) for 12 h. Results: The ROS production and cell death were induced by PMA treatment, and exposure to DB reduced the PMA induced downregulation of cell survival. The PMA and DB treatments upregulated the lipid accumulation, with corresponding increase in the acetyl-CoA carboxylase alpha, fatty acid synthase mRNA expressions. DB-PMA co-treatment reduced the glycolysis genes expression, but increased the expressions of fatty acid oxidation and TCA cycle genes. Conclusion: This study provides new insights and directions for further research relating to the immunity of porcine respiratory system, by employing a model based on alveolar macrophages and natural materials.