• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5473-5476
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• 2013

Background: In our study, the LDH, albumin, hemoglobin, neutrophile, thrombocyte, lymphocyte counts and prognostic significance of neutrophile-lymphocyte and thrombocyte-lymphocyte ratios in NSCLC derived from these counts obtained during regular examinations of patients were examined. Materials and Methods: Histopathologically diagnosed non-small-cell-lung cancer patients between 2008 and 2010 were included in the study. Before the treatment, full blood count including routine lymphocyte count, blood biochemistry examinations including liver (AST, ALT, total protein, Albumin), LDH and kidney (BUN, Cre) function tests were performed. Results: A total of 156 patients, 76 of whom (48.7%) were female and 80 of whom (51.3%) were male were included. Mean hemoglobin level was determined as 12. Overall survival was found to be significantly dependent on whether patients were anemic or not (p: 0.005). Mean LDH level was determined as 233.4. There was nosurvival difference between patients with and without high LDH (p: 0.532). In patients where NLR showed systemic inflammatory response, overall survival was 10.8 months whereas this duration was 19.6 months in patients where the systemic inflammatory response was negative (p: 0.012). In patients where TLR showed systemic inflammatory response, overall survival was 13.6 months whereas this duration was 21.9 months in patients where the systemic inflammatory response was negative (p: 0.04). Conclusions: Molecular methods have been changing rapidly in today's world and they manage the treatment besides defining the prognosis of patients. However, easily accessible and cheap laboratory parameters should be considered in the prognosis of patients besides these new methods.

• 분석과학
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• 제28권1호
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• pp.1-7
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• 2015

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific nitrosamine found only in tobacco products. The ability to monitor biomarker concentrations is very important in understanding environmental tobacco smoke (ETS). In this study, an efficient and sensitive method for the analysis of NNK in dust was developed and validated using liquid chromatography tandem mass spectrometry. Dust was collected with filter paper soaked in methanol. The standard solution and dust sample were diluted with 100 mM ammonium acetate and extracted using dichloromethane. Our calibration curves ranged from 25 to $10^4pg/mL$. Excellent linearity was obtained with correlation coefficient values between 0.9996 and 1.0000. The limit of detection (LOD) was 5 pg/mL ($S/N{\geq}3$) and the retention time was 10 min. The limit of quantification (LOQ) was 25 pg/mL, and the acceptance criteria was the rate of 98-103% (80-120% at levels up to $3{\times}LOQ$). The coefficient of variations (CV) was 2.8%. Accuracies determined from dust samples spiked with four different levels of NNK racurves ranged that from 25 to 104 pg/mL. Excellent linearity was obtained between 92.1% and 114%. The precision of the method was acceptable (5% of CV). The recovery rates of the whole analytical procedure at low, medium, and high levels were 105.7-116.5% for NNK. The carry-over effects during LC-MS/MS analysis were not observed for NNK. This manuscript summarizes the scientific evidence on the use of markers to measure ETS.

• 대한한방종양학회지
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• 제6권1호
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• pp.165-180
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• 2000

Clinical studies were carried out 83 cases of patients with colorectal cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by colorectal cancer, by sex, showed that Male is more then Female, by age, showed that the number of fifties is majority. 2. Distribution of diagnostic stage, in descending order; stage III(53%, top), stage IV(45.8%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(92.1%) were observed. The effects of the symptoms were as follows: diarrhea(37.3%), abdominal pain (25.3%), general body weakness(22.9%), nausea(20.5%) and etc. in orders. 4. Analysis of hematology attached by colorectal cancer, maintenance and increasing of WBC(89.9%), RBC(74.7%), Hgb(81.1%), Platelet(92.4%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(85.9%), ALT(94.8%), GTP(87.5%), Creatinine(90.9%) were observed. 5. of IL-12 and $IFN-\gammer$ attached by colorectal cancer, increasing of IL-12(53.3%), IFN-{\gammer}(80%)$) were observed. 6. Analysis of QOL attached by colorectal cancer, maintenance and improvement of combined treatment of western and oriental therapy(89.6%), traditional oriental therapy(83.3%) were observed. 7. Analysis of survival in patients with IV stage of colorectal cancer, above 7 months(18.4%), 12 months(65.8%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(83.3%) and maintenance and improvement of combined treatment of western and oriental therapy(80.5%) were observed. Analysis of tumor marker attached by colorectal cancer, maintenance and decreasing of CEA(78.8%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(83.3%), combined treatment of western and oriental therapy(72.7%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for colorectal cancer patients by combination with western therapy or alone.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.817-819
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• 2013

Background: The present study was designed to comparatively assess alteration of biochemical parameters in bile duct cancer and gall stone disease. Materials and Methods: A hospital based case-control study was carried out in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January 2010 and $31^{st}$ December 2012. The variables collected were age, gender, serum total cholesterol, total bilirubin, AST, ALT, serum alkaline phosphatase, albumin and hemoglobin. One way ANOVA was used to examine the statistical significance of differences between groups. A post-hoc LSD test was applied for the comparison of means of control versus case groups. A p-value of <0.05 (two-tailed) was considered significant. Results: The mean age of cases and controls was $53.2{\pm}21.2$ years. The levels of serum cholesterol were higher in cases of cancer $192.5{\pm}21.5$ mg/dl in comparison to stone cases $168.7{\pm}16.1$ mg/dl (p value: 0.0001). The total bilirubin showed the marked difference in cases of cancer $7.6{\pm}3.2$ mg/dl in comparison to stone cases $2.5{\pm}0.8$ mg/dl of bile duct. There was discernible divergence in values of alkaline phosphatase in cases of cancer $251.5{\pm}20.1$ IU/l when compared to stone cases $173.2{\pm}12.6$ IU/l of bile duct. In contrast, there was no apparent deviation in values of aspartate transaminases and alanine transaminases in cases of cancer $59.1{\pm}8.9$ IU/l and $105.5{\pm}26.5$ IU/l when compared to stone cases $56.9{\pm}7.9$ IU/l and $84.5{\pm}13.5$ IU/l respectively. Conclusions: LFT analysis for pre-operative assessment was a good predictive marker in setting apart bile duct cancer and gall bladder stone.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1789-1794
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• 2015

Background: Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. Objectives: To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. Materials and Methods: One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ${\geq}7$ kPa was used to define significant hepatic fibrosis. Results: Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Conclusions: Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.

• Toxicological Research
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• 제28권1호
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• pp.57-65
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• 2012

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

• 분석과학
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• 제35권4호
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• pp.161-168
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• 2022

Wheat is rich in sources of fiber, oligosaccharides, and resistant starch, simple carbohydrates which may have a protective role against carcinoma. Additionally, Whole wheat/bran as well includes contains phytochemicals such as flavonoids, lignans, folate, phytosterols, phenolic acids, and tocols. The above phytochemicals suitable forms antioxidant and cholesterol-reducing activities. Phytoestrogens are regarded as especially essential in the preventative measures of hormonally dependent malignancies such as breast cancer (BC). In this study lowered BC risk has been associated with whole grain/bran consumption with an odds ratio (OR=0.24 and 95 %CI=0.10-0.56). Wheat/bran appears to have a reliable protective impact against BC. While intake of white bread has been associated with a high risk of BC (OR=2.63 and CI 95 %=1.07-6.48). Also, the E-Selectin (SELE) Single nucleotide polymorphisms (SNPs) rs5353 A/G and rs932307 C/T were investigated using the sanger sequences approach. There was a positive association between genotypes (rs5353 GG+AG) and (rs932307 TT+CT) with rate consumption of wheat-white/bread and these genotypes were more frequent in patients had BC in comparison with a significant difference (P=0.03) (P=0.01), respectively. The genotypes (GG+AG) frequency of the rs5353 polymorphism and (TT+CT) genotypes of the rs932307 polymorphism in the present study had a high risk of cancer with (OR=3.05), (OR=4.17) respectively. While these genotypes showed no significant association with the rate of whole grain consumption in patients and control. Therefore, the type of wheat may associate with increased incidence of disease-related with type of Polymorphism because some present genotypes of SNPs showed high (OR) which may refer to their positive associated with disease, the white wheat consumption may active the risky association between SNPs and BC.

• 생명과학회지
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• 제26권11호
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• pp.1282-1288
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• 2016

본 연구는 섬애약쑥의 생리활성 규명을 위한 연구의 일환으로 물 추출물의 항염증 활성 및 간 염증에 대한 보호효과를 세포수준에서 확인하였다. 세포독성이 없는 $100{\sim}400{\mu}g/ml$의 농도 범위에서 섬애약쑥 추출물은 HepG2 세포에서 nitric oxide (NO)와 reactive nitrogen species (ROS)생성을 농도의존적으로 저해하였으며, 간염질환과 밀접한 관계가 있는 cytokine인 M-CSF와 IL-8의 발현을 감소시켰다. 또한 직접적인 간 손상을 나타낼 수 있는 지표인 AST와 ALT의 발현을 유의성 있게 감소시키는 결과를 얻을 수 있었다. 본 실험을 통해서 섬애약쑥물 추출물은 세포독성이 없는 $200{\sim}400{\mu}g/ml$의 범위에서 농도의존적으로 간 염증의 개선 효과를 가질 것이라는 단서를 확인하였다.