• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5289-5296
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• 2015

Background: Despite the decreased incidence, gastric cancer is still a frequent cause of cancer related death. The 1st line 2 or 3 drugs regimen is still a debatable issue. HER2 targeted therapy has emerged as the standard of care, but it is unavailable in the Brazilian Public Health System. The end-point of this trial was overall survival (OS) in patients with metastatic gastric cancer treated in a public university hospital in Brazil. The secondary end-points were efficacy and safety of regimens with 2 (F+P) or 3 (EOX) drugs to develop an institutional guideline to facilitate optimal treatments. Materials and Methods: In this retrospective study, 1st line regimens were evaluated for OS and PFS stratified by age and ECOG using Cox regression. Results: 47 patients were treated over the last 3 years. In 1st line, 29 were treated with F+P (mean 59.3 years, 34.5% ECOG 2 and a mean of 5.69 cycles) and 16 with EOX (mean 47 years, 18.8% ECOG 2 and a mean of 5.44 cycles). The median OS was 13.8 months (95%CI 10.7-16.9). Response was evaluated in 40 cases and was 64.3% for EOX and 37.5% for F+P (p=0.25). The median PFS was 9.5 months for EOX and 5.6 months for F+P (HR 0.85, 95%CI 0.41-1.74). However, among patients with ECOG 2 mPFS was 3.70 vs 5.40 months, respectively (p=0.86). Regimens showed similar manageable adverse events. A total of 34 patients suffered progression and 14 received $2^{nd}$ line therapy. Diffuse histology (HR 1.89, 95%CI 1.22-2.88), achieving 2nd line (HR: 0.25, 95%CI 0.11-0.58) and treatment response (HR 0.23, 95%CI 0.12-0.47) were OS prognostic factors. Conclusions: Patients treated in our hospital had outcomes compatible with the literature. The regimen choice should be related to patient features. Second line treatment should be considered.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5263-5272
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• 2012

Background: Gastric cancer (GC) is one of the most common cancers in China. Adjuvant chemotherapy (AC) is a routine auxiliary treatment for GC recommended by the guidelines issued in 2011 by the Ministry of Health of the People's Republic of China, but the relevant credible consequences in China have been insufficient because of China's late start and ethical concerns. Methods: A series of databases, including Cochrane Library, MEDLINE, EMBASE, the Chinese database of the National Knowledge Infrastructure and the VIP database, were searched by 2 reviewers independently for studies investigating AC for GC through March 2012. The retrieved literature was screened according to the eligibility criteria. Results: A total of 35 randomized control trials (RCTs) were subjected to the final analysis, including 4,043 patients in treatment group and 3,884 in the control group, as well as 4 clinical-control trials (CCTs), which accessed the final analysis with 238 and 252 patients, respectively. AC reduced the risk of death as a protective treatment with statistical significance (HR=0.91, 95%CI: [0.85, 0.97], P=0.002), and it seemed more effective for Asian than non-Asian patients. The effects of AC were not influenced by the starting time (P>0.05). D2 lymphadenectomy-based chemotherapy was effective (HR=0.89, 95%CI: [0.80, 0.99], P=0.04). Oral S-1 40 mg/m2 after D2 lymphadenectomy might be a better choice for Asians with advanced GC and might result in a greater reduction of adverse events than in non-Asian patients. GRADE quality assessment determined that the strength of the evidence from foreign studies from Europe, the United States and Asian countries other than China was high, while it was moderate for Chinese studies. Conclusion: AC was effective or even curative in Chinese patients in general, although it is still necessary to optimize a targeted AC scheme for Chinese patients with GC.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.33-39
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• 1996

Purpose : This study was done to analyze survivals, patterns of failure, and complications of early uterine cervix cancer after curative radiotherapy. Materials and Methods : Eighty patients with uterine cervix cancer FIGO Stage IB (48 cases) and Stage IIA (32 cases) treated with radiotherapy were analyzed retrospectively. Patients were treated from November 1985 to May 1993, and minimum follow up period was 24 months and 6 cases were lost to follow up. All of them were treated with external radiotherapy and different fractions of high dose rate intracavitary radiotherapy, Survival rates, failure patterns, complication rates and degrees of severity were analyzed according to several factors. Results : Overall 5 year survival rate and relapse free survival rate were $72.3\%$, and $72.8\%$ respectively. Prognostic factors were stage, size, pathology, RT response and there was no significant survival difference among the reasons of radiotherapy choice. There were 19 cases of treatment failure, another 3 cases were not tumor related death, and most of treatment related failure occurred within 24 months Late complication rate of bladder and rectum were $8.8\%,\;15\%$ respectively, frequency and severity of complication were correlated with ICR fractionation dose and total dose. Conclusion : These results showed that survival rates of early stage radiation treated cervix cancer patients were comparable to surgical series, but more aggressive treatment methods needed for stage IIA poor prognostic patients. To decrease late complication, choice of proper ICR dose and meticulous vaginal packing is needed.

• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.648-657
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• 2015

H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction, respectively; immunohistochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced the cleavage of proapoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly(ADP)-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosisinducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in the G1/S phase. In addition, the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.270-281
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• 2010

Total parenteral nutrition (TPN) is necessary to neonates in neonatal intensive care unit (NICU) for survival and growth because of impossible of enteral feeding. Long-term TPN can be associated with a broad spectrum of hepatobiliary disorder, ranging from mild hepatic dysfunction to severe end-stage liver disease. Cholestasis developed most commonly in neonate, ursodeoxycholic acid (UDCA) is widely used in adult with cholestatic and non-cholestatic liver diseases but there have been limited data on the effects in neonate with PNAC. This study was performed retrospectively to review all medical histories of the total 30 neonates with was administrated UDCA for treatment to parenteral nutrition associated cholestasis (PNAC) at Chungbuk National University Hospital NICU from April 2002 to December 2008. UDCA was administrated at bilirubin is over 2 mg/dl. The criterias for drug evaluation were included hepatic biochemical marker such as direct bilirubin, total bilirubin, AST, ALT, ALP and GGT, TPN therapy period, cholestasis development period, UDCA treatment period, UDCA dosage and adverse effect. In the results, Post-UDCA treatment significant was decreased direct bilirubin, total bilirubin, AST and ALP (p<0.05), and was decreased GGT (p>0.05) and slightly was increased ALT (p>0.05). Reffective timect biDCA was appear at mean $10.5{\pm}1.3$ days, iDCA administration period was mean $64.4{\pm}5.9$ days, cholestasis period was mean $71.9{\pm}6.4$ days and UDCA dosage was mean $22.9{\pm}0.9$ mg/kg/day. Common adverse effects is diarrhea, 5 patients arised mild diarrhea but it possible also related with increased enteral feeding. In conclusion, iDCA can decrease direct bilirubin that major parameter t bcholestasis and oher hepatic biochemical makers. UDCA is effective on PNAC without any serious side effect and cost-effective. Although no greatly shortening cholestasis period, but can protect to develop into severe liver disease and other complication or death. Based on these result, UDCA is recommended for treatment of cholestasis at direct bilirubin is over 2 mg/dl.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Radiation Oncology Journal
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• v.37 no.3
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• pp.176-184
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• 2019

Purpose: It is unclear whether adding concurrent chemotherapy (CT) to definitive radiotherapy (RT) following induction CT is a tolerable and cost effective treatment for non-small-cell lung cancer (NSCLC) patients aged 70 years or older with comorbidities. This study evaluated the actual clinical outcomes between concurrent chemoradiotherapy (CCRT) and RT alone following induction CT or not in patients (≥70 years) in a single institution's clinical practice. Materials and Methods: A total of 82 patients with unresectable stage III NSCLC between 2004 and 2016 were retrospectively analyzed. Their treatment tolerance and clinical outcomes such as overall survival (OS), locoregional recurrence (LRR), treatment toxicities and distant metastasis (DM) were evaluated. Early mortality rates were also evaluated as 4-month mortality after RT. Results: Fifty-four patients received CCRT and 28 patients received RT alone. Induction CT before RT was performed for 68.5% and 50.0% in CCRT and RT alone groups. Treatment tolerance was significantly worse in CCRT (p = 0.046). The median survival was 21.1 and 18.1 months for CCRT and RT alone, which was not statistically significant. LRR and DM were also not different. Most early deaths after CCRT were attributed to non-cancer-related mortality. Acute esophagitis of grade ≥2 occurred more following CCRT (p = 0.017). In multivariate analysis, a Charlson Comorbidity Index (CCI) of ≥5 and a weight loss of ≥5% after RT were associated with poor OS. The factors adversely affecting 4-month survival were a CCI of ≥5 and CCRT. Conclusion: There were no significant differences in OS, LRR, and DM between CCRT and RT alone treatment in elderly patients. However, there was a poorer tolerance and higher incidence of acute esophagitis in the CCRT group. Specifically, when the patients had a CCI of ≥5, RT alone seems to be reasonable with a low probability of early death.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.163-170
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• 2006

Nardostachyos Rhizoma (N. Rhizoma) belonging to the family Valerianaceae has been anti-arrhythmic effect, and sedation to the central nerve and a smooth muscle. We reported that the water extract of N. Rhizoma induced apoptotic cell death and differentiation in human promyelocytic leukemia (HL-60) cells. Cytotoxicity of N. Rhizoma was detected only in HL-60 cells (IC50 is about 200 ${\mu}g/ml$). The cytotoxic activity of N. Rhizoma in HL-60 cells was increased in a dose-dependent manner. We used several measures of apoptosis to determine whether these processes were involved in N. Rhizoma-induced apoptotic cell death. The high-dose (200 ${\mu}g/ml$) treatment of N. Rhizoma to HL-60 cells showed cell shrinkage, cell membrane blobbing, apoptotic bodies, and the fragmentation of DNA, suggesting that these cells underwent apoptosis. Treatment of HL-60 cells with N. Rhizoma time-dependently induced activation of caspase-3, caspase-8, and caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase. Also, we investigated the effect of N. Rhizoma on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells was determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide assay, respectively. N. Rhizoma induced the differentiation of HL-60 at the low-dose (100 ${\mu}g/ml$) treatment, as shown by increased expression of differentiation surface antigen CD11b, but not CDl4 and increased reducing activity of NBT. When HL-60 cells were treated with N. Rhizoma at concentration of $50{\mu}g/ml\;and\;100{\mu}g/ml$, NBT-reducing activities induced approximately 1.5-fold and 20.0-fold as compared with the control. In contrast, HL-60 cells treated with the N. Rhizoma-ATRA combination showed markedly elevated levels of 26.3-fold at $50{\mu}g/ml$ N. Rhizoma-0.1 ${\mu}M$ ATRA combination and 27.5-fold at 50 ${\mu}g/ml$ N. Rhizoma-0.2 ${\mu}M$ ATRA combination than when treated with N. Rhizoma alone or ATRA alone. It may be that N. Rhizoma plays important roles in synergy with ATRA during differentiation of HL-60 cells. DNA flow-cytometry indicated that N. Rhizoma markedly induced a G1 phase arrest of HL-60 cells. N. Rhizoma-treated HL-60 cells increased the cell population in G1 phase from 32.71% to 42.26%, whereas cell population in G2/M and S phases decreased from 23.61% to 10.33% and from 37.78% to 33.98%, respectively. We examined the change in the $p21^{WAF1/Cip1}\;and\;p27^{Kip1}$ proteins, which are the CKIs related with the G1 phase arrest. The expression of the CDK inhibitor $p27^{Kip1},\;but\;not\;p21^{WAF1/Cip1}$ were markedly increased by N. Rhizoma. Taken together, these results demonstrated that N. Rhizoma induces apoptotic cell death through activation of caspase-3, and potently inhibits the proliferation of HL-60 cells via the G1 phase cell cycle arrest in association with $p27^{Kip1}$ and granulocytic differentiation induction .

• Journal of Preventive Medicine and Public Health
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• v.11 no.1
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• pp.123-127
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• 1978

The major objective of this research is to identify those hospital characteristics that best explain cost variation among hospitals and to formulate linear models that can predict hospital costs. Specific emphasis is placed on hospital output, that is, the identification of diagnosis related patient groups (DRGs) which are medically meaningful and demonstrate similar patterns of hospital resource consumption. A casemix index is developed based on the DRGs identified. Considering the common problems encountered in previous hospital cost research, the following study requirements are estab-lished for fulfilling the objectives of this research: 1. Selection of hospitals that exercise similar medical and fiscal practices. 2. Identification of an appropriate data collection mechanism in which demographic and medical characteristics of individual patients as well as accurate and comparable cost information can be derived. 3. Development of a patient classification system in which all the patients treated in hospitals are able to be split into mutually exclusive categories with consistent and stable patterns of resource consumption. 4. Development of a cost finding mechanism through which patient groups' costs can be made comparable across hospitals. A data set of Medicare patients prepared by the Social Security Administration was selected for the study analysis. The data set contained 27,229 record abstracts of Medicare patients discharged from all but one short-term general hospital in Connecticut during the period from January 1, 1971, to December 31, 1972. Each record abstract contained demographic and diagnostic information, as well as charges for specific medical services received. The 'AUT-OGRP System' was used to generate 198 DRGs in which the entire range of Medicare patients were split into mutually exclusive categories, each of which shows a consistent and stable pattern of resource consumption. The 'Departmental Method' was used to generate cost information for the groups of Medicare patients that would be comparable across hospitals. To fulfill the study objectives, an extensive analysis was conducted in the following areas: 1. Analysis of DRGs: in which the level of resource use of each DRG was determined, the length of stay or death rate of each DRG in relation to resource use was characterized, and underlying patterns of the relationships among DRG costs were explained. 2. Exploration of resource use profiles of hospitals; in which the magnitude of differences in the resource uses or death rates incurred in the treatment of Medicare patients among the study hospitals was explored. 3. Casemix analysis; in which four types of casemix-related indices were generated, and the significance of these indices in the explanation of hospital costs was examined. 4. Formulation of linear models to predict hospital costs of Medicare patients; in which nine independent variables (i. e., casemix index, hospital size, complexity of service, teaching activity, location, casemix-adjusted death. rate index, occupancy rate, and casemix-adjusted length of stay index) were used for determining factors in hospital costs. Results from the study analysis indicated that: 1. The system of 198 DRGs for Medicare patient classification was demonstrated not only as a strong tool for determining the pattern of hospital resource utilization of Medicare patients, but also for categorizing patients by their severity of illness. 2. The wei틴fed mean total case cost (TOTC) of the study hospitals for Medicare patients during the study years was $11,27.02 with a standard deviation of $117.20. The hospital with the highest average TOTC ($1538.15) was 2.08 times more expensive than the hospital with the lowest average TOTC ($743.45). The weighted mean per diem total cost (DTOC) of the study hospitals for Medicare patients during the sutdy years was $107.98 with a standard deviation of $15.18. The hospital with the highest average DTOC ($147.23) was 1.87 times more expensive than the hospital with the lowest average DTOC ($78.49). 3. The linear models for each of the six types of hospital costs were formulated using the casemix index and the eight other hospital variables as the determinants. These models explained variance to the extent of 68.7 percent of total case cost (TOTC), 63.5 percent of room and board cost (RMC), 66.2 percent of total ancillary service cost (TANC), 66.3 percent of per diem total cost (DTOC), 56.9 percent of per diem room and board cost (DRMC), and 65.5 percent of per diem ancillary service cost (DTANC). The casemix index alone explained approximately one half of interhospital cost variation: 59.1 percent for TOTC and 44.3 percent for DTOC. Thsee results demonstrate that the casemix index is the most importand determinant of interhospital cost variation Future research and policy implications in regard to the results of this study is envisioned in the following three areas: 1. Utilization of casemix related indices in the Medicare data systems. 2. Refinement of data for hospital cost evaluation. 3. Development of a system for reimbursement and cost control in hospitals.