• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.36-42
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• 2013

Background/Aims: Gemcitabine is regarded as a reference regimen for advanced pancreatic cancer and shows relatively safe toxicity profiles compared with other cytotoxic agents. However, many oncologists are appeared to be still reluctant to treat elderly pancreatic cancer patients with cytotoxic chemotherapy because of predicted low response rate and potential adverse events. Methods: All patients who were received gemcitabine based chemotherapy between 2007 and 2010 were identified and clinical, laboratory, radiographic data were retrospectively reviewed. Patients were divided into two groups based on their ages: less than 65, and equal or more than 65 years old. Gemcitabine, at a dose of 1,000 mg per square meter of body surface area, was administered by intravenously over 30 minutes weekly for 3 weeks followed by 1 week rest, alone or along with other chemotherapeutic agents including cisplatin, capecitabine and erlotinib. Results: A total of 61 patients were identified and all patients were not eligible to receive operation because of advanced stage at diagnosis. Twenty three patients (37.7%) were equal or more than 65 year of age. Mean age was 56 years old and 71 years old in each group. Laboratory data including CA 19-9 were not significantly different. More gemcitabine monotherapy was delivered (56.5% vs. 26.3%, p=0.029) and less second or third line therapy was adminis- tered (17.4% vs. 50.0%, p=0.014) in elderly group. Cholangitis occurred and stent placement were performed similarly in both groups. Conclusion: Gemcitabine based chemotherapy can be administered safely to elderly pancreatic cancer patients and comparable response rate and progression free survival can be expected as young patients.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.116-122
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• 2002

Purpose : A randomized prospective study was conducted to compare the efficacy of early or late alternating schedules of radiotherapy, and carboplatin and ifosfamide chemotherapy in patients with limited-disease small cell lung cancer. Materials and Methods: From August 1993 to August 1996, a total of 44 patients with newly diagnosed, limited-disease small cell lung cancer, PS $H0\~2$, wt $loss<10\%$ were enrolled in a randomized trial which compared early alternating radiotherapy (RT)/chemotherapy (CT) and late alternating RT/CT. The CT regimen included ifosfamide $1.5\;g/m^2$ IV, d1-5 and carboplatin AUC 5/d IV, d2 peformed at 4 week intervals for a total of 6 cycles. RT (54 Gy/30 fr) was started after the first cycle of CT (early arm, N=22) or after the third cycle of CT (late arm, N=22) with a split course of treatment. Results : The pretreatment characteristics between the two arms were well balanced. The response rates in the early $(86\%)$ and late $(85\%)$ arm were similar. The median survival durations and 2-year survival rates were 15 months and $22.7\%$ in the early arm, and 17 months and $14.9\%$ in the late arm (p=0.47 by the log-rank test). The two-year progression free survival rates were $19.1\%$ in the early arm and $19.6\%$ in the late arm (p=0.52 by the log-rank test). Acute grade 3 or 4 hematologic and nonhematologic toxicities were similar between the two arms. Eighteen patients $(82\%)$ completed 6 cycles of CT in the early arm and 17 $(77\%)$ in the late arm. Four patients received less than 45 Gy of RT in the early arm and two in the late arm. There was no significant difference in the failure patterns. The local failure rate was $43\%$ in the early arm and $45\%$ in the late arm. The first site of failure was the brain in $24\%$ of the early arm patients compared to $35\%$ in the late arm (p=0.51). Conclusion : There were no statistical differences in the overall survival rate and the pattern of failure between the early and late alternating RT/CT in patients with limited-disease small cell lung cancer.

• Herbal Formula Science
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• v.23 no.2
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• pp.199-208
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• 2015

Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

• Journal of Korean Neurosurgical Society
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• v.64 no.4
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• pp.592-607
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• 2021

Objective : Few studies exist on primary spinal cord tumors (PSCTs) in pediatric patients. The purpose of this study was to perform descriptive analysis and detailed survival analysis for PSCTs. Methods : Between 1985 and 2017, 126 pediatric patients (male : female, 56 : 70) with PSCTs underwent surgery in a single institution. We retrospectively analyzed data regarding demographics, tumor characteristics, outcomes, and survival statistics. Subgroup analysis was performed for the intramedullary (IM) tumors and extradural (ED) tumors separately. Results : The mean age of the participants was 6.4±5.04 years, and the mean follow-up time was 69.5±46.30 months. The most common compartment was the ED compartment (n=57, 45.2%), followed by the IM (n=43, 34.1%) and intradural extramedullary (IDEM; n=16, 12.7%) compartments. Approximately half of PSCTs were malignant (n=69, 54.8%). The most common pathologies were schwannomas (n=14) and neuroblastomas (n=14). Twenty-two patients (17.5%) died from the disease, with a mean disease duration of 15.8±15.85 months. Thirty-six patients (28.6%) suffered from progression, with a mean period of 22.6±30.81 months. The 10-year overall survival (OS) rates and progression-free survival (PFS) rates were 81% and 66%, respectively. Regarding IM tumors, the 10-year OS rates and PFS rates were 79% and 57%, respectively. In ED tumors, the 10-year OS rates and PFS rates were 80% and 81%, respectively. Pathology and the extent of resection showed beneficial effects on OS for total PSCTs, IM tumors, and ED tumors. PFS was affected by both the extent of removal and pathology in total PSCTs and ED tumors; however, pathology was a main determinant of PFS rather than the extent of removal in IM tumors. The degree of improvement in the modified McCormick scale showed a trend towards improvement in patients with IM tumors who achieved gross total removal (p=0.447). Conclusion : Approximately half of PSCTs were malignant, and ED tumors were most common. The most common pathologies were schwannomas and neuroblastomas. Both the pathology and extent of resection had a decisive effect on OS. For IM tumors, pathology was a main determinant of PFS rather than the extent of removal. Radical excision of IM tumors could be a viable option for better survival without an increased risk of worse functional outcomes.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.796-805
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• 1997

Background : It is clear that deregulation of cell cycle progression is a hallmark of neoplastic transformation and genes involved in the $G_1$/S transition of the cell cycle are especially frequent targets for mutations in human cancers, including lung cancer. p16 gene product, one of the G1 cell-cycle related proteins, that is recently identified plays an important role in the negative regulation of the the kinase activity of the cyclin dependent kinase (cdk) enzymes. Therefore p16 gene is known to be an important tumor suppressor gene and is also called MTS1 (multiple tumor suppressor 1). No more oncogenes have been reported to be frequently related to multiple different malignancies than the alterations of p16 gene. Especially when it comes to non-small cell lung cancer, there was no expression of p16 in more than 70% of cell lines examined. And also it is speculated that p16 gene could exert a key role in the development of non-small cell lung cancer. This study was designed to evaluate whether p16 gene could be used as a candidate for gene therapy of non-small cell lung cancer. Methods : After the extraction of total RNA from normal fibroblast cell line and subsequent reverse transcriptase reaction and polymerase chain reaction, the amplified p16 cDNA was subcloned into eukaryotic expression plasmid vector, pRC-CMV. The constructed pRC-CMV-p16 was transfected into the NCI-H441 NSCLC cell line using lipofectin. The changes of G1 cell-cycle related proteins were investigated with Western blot analysis and immunoprecipitation after extraction of proteins from cell lysates and tumor suppressive effect was observed by clonogenic assay. Results : (1) p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 showed the formation of p16 : cdk 4 complex and decreased phosphorylated Rb protein, while control cell line did not. (2) Clonogenic assay demonstrated that the number of colony formation was markedly decreased in p16(-) NCI-H441 cell line transfected with pRC-CMV-p16 than the control cell line. Conclusion : It is confirmed that the expression of p16 protein in p16 absent NSCLC cell line with the gene transfection leads to p16 : cdk4 complex formation, subsequent decrease of phosphorylated pRb protein and ultimately tumor suppressive effects. And also it provides the foundation for the application of p16 gene as a important candidate for the gene therapy of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.60-71
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• 2000

Backgrounds : Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. Method : Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). Results : Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung canær (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T -factor, nodal involvement, differentiation Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with prognosis showed that nodal involvement was the only independent prognostic factor in all patients. Conclusion : Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.475-484
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• 2002

Background : Unresectable non-small cell lung cancer has a poor response to chemotherapy and has an unfortunate prognosis. More effective and less toxic cytotoxic agents are needed to improve the outcome of these patients. The efficacy and safety of vinorelbine monotherapy in these advanced lung cancer patients was evaluanted. Materials and Methods : Sixteen patients with non-small cell lung cancer in stage III or IV, who received vinorelbine alone as an initial anticancer chemotherapy from June 1996 to December 2000 were enrolled in this study. Vinorelbine was given intravenously at a dose 30mg/$m^2$ every week. Results : A mong the sixteen patients, six had a partial response(38%) and the median survival was 16 weeks. The median response duration was 27 weeks (95% CI 6-47), and the time to progression was 16 weeks(95% CI 6-26). Among a total of 112 cycles, neutropenia(WHO grade 3 or 4) and anemia(grade 3) occurred in 9% and 3%, respectively. Only 1 patient required hospitalization for neutropenic fever. Non-hematologic toxicity was minor and was easily controlled. Conclusion : Vinorelbine monotherapy was well tolerated, and moderately effective in patients with advanced non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.145-152
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• 2009

Purpose: We retrospectively studied the outcomes and prognostic factors of patients with locally advanced, unresectable pancreatic cancer who were treated with concurrent chemoradiotherapy (CCRT) or radiotherapy only. Materials and Methods: Fifty-one patients with locally advanced, unresectable pancreatic cancer (stage IIA~III) who recevied radiotherapy ($\geq$30 Gy) between January 1994 and August 2008 were reviewed retrospectively. The median radiation dose was 39 Gy. Chemotherapy consisted of gemcitabine, cisplatin, or 5-FU alone or in various combinations, and was administered concurrently with radiotherapy in 38 patients. Results: The follow-up period ranged from 2~40 months (median, 8 months). The median survival, and the 1-and 2-year overall survival (OS) rates were 7 months, 15.7%, and 5.9%, respectively. Based on univariate analysis, the baseline CA19-9, performance status, and chemotherapy regimen were significant prognostic factors. The median survival was 8 months for CCRT, and 6 months for radiotherapy alone. The patients treated with gemcitabine-containing regimens had longer survival (median, 10 months) than the patients treated with radiotherapy alone (p=0.027). Twenty-three patients were available to evaluate the patterns of failure. Distant metastases (DM) occured in 18 patients and regional recurrences were demonstrated in 4 patients. Local progression developed in 14 patients. We analyzed the association between the time-to-DM and the baseline CA19-9 levels for 18 evaluable patients. The median time-to-DM was 20 months for patients with normal baseline CA19-9 levels and 2 months for patients with baseline CA19-9 levels $\geq$200 U/ml. Conclusion: CCRT with gemcitabine-based regimens was effective in improving OS in patients with locally advanced, unresectable pancreatic cancer. We suggest that the baseline CA19-9 level is valuable in determining the treatment strategy for patients with locally advanced, unresectable pancreatic cancer.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.909-921
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• 2000

Background : Defects in apoptotic signaling pathways play important role in tumor initiation, progression, metastasis and resistance to treatment. Several proteins which may promote tumorigenesis by inhibiting apoptosis were identified. The survivin protein is the member of inhibitor of apoptosis protein(IAPs) family which inhibits apoptosis. Unlike other IAPs, it is expressed in during the fetal period but not in adult differentiated tissues. Many reports have stated that survivin is selectively expressed in many cancer cell lines and cancer tissues. We performed immunohistochemical analysis for survivin expression in non-mall cell lung cancer to get evaluate its clinical implication. Methods : Twenty nine surgically resected lung cancers were examined. Immunohistochemical staining were performed by immuno-peroxidase technique using avidin-biotinylated horseradish pemxidase complex in the formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section. Anti-survivin polyclonal antibody was used for primary antibody and anti-p53 monoclonal antibody was also used to analyze the correlation between survivin and p53 expression. The survivin expression scores were determined by as the sum of the stained area and intensity. Results : Immunohistochemical analysis showed cancer specific expression of survivin in 20 of 29 cases (69.0%). Western blot analysis also showed the selective survivin expression in tumor tissue. There was no correlation between survivin expression and clinicopathological parameters and prognosis. We analyzed the ∞π'elation between survivin expression and p53 expression, but found none. Conclusion: We confirmed the tumor specific expression of survival in non-small cell lung canær. But this expression was not correlated with clinical parameters as well as histology, tumor stage, recurrence, and survival rate. Also it was not statistically correlated with the expression of p53.