• Title/Summary/Keyword: COX-1, COX-2

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Prognostic Value of Preoperative Serum Alpha- Fetoprotein Level in Resectable Gastric Cancer (절제 가능한 위암 환자에서 수술 전 혈청 알파태아단백치 측정의 의의)

  • Yu, Wan-Sik;Kim, Tae-Bong
    • Journal of Gastric Cancer
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    • v.3 no.1
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    • pp.33-37
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    • 2003
  • Purpose: Alpha-fetoprotein (AFP) is widely accepted as a useful tumor marker for diagnosis of hepatocellular carcinomas. On rare occasions, however, an abnormal elevation of serum AFP also has been reported in an adenocarcinoma of the gastrointestinal tract. We evaluated the influence of preoperative abnormal elevation of serum AFP (AFP positivity) on the prognosis of resectable gastric cancers. Materials and Methods: 812 gastric cancer patients, who were investigated for serum AFP before their operations and who underwent gastric resections with D2 or more extended lymph node dissection, were enrolled in the study. The survival rates were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. Results: Fifty patients ($6.2\%$) were AFP positive (10.1. 4322.6 ng/ml). The survival rate of the AFP positive group was significantly lower than that of the AFP negative group ( $46.6\%\;vs.\;67.0\%$; P=0.0002). The depth of tumor invasion, the degree of regional lymph node metastasis, distant metastases, the TNM stage, the gross type, differentiation, the extent of gastric resection, and the curability of the surgery also significantly influenced survival. Multivariate analysis revealed that the depth of tumor invasion, the degree of regional lymph node metastasis, the curability of the surgery, and AFP positivity were independent prognostic indicators. Conclusion: Preoperative serum AFP can be used as an independent prognostic factor of resectable gastric cancer.

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Antitumorigenic Effect of a High Protein Diet in Mouse Skin

  • Tak, Ka-Hee;Kim, Eun-Jung
    • Preventive Nutrition and Food Science
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    • v.16 no.4
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    • pp.283-290
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    • 2011
  • The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.

Antioxidant and Anti-inflammatory Effect of Nardostachys Chinensis in IFN-$\gamma$/LPS-stimulated Peritoneal Macrophage (감송향의 in vitro 항산화 및 항염증 효과)

  • Baek, Seol;Choi, Jae-Hyuk;Ko, Sung-Hoon;Lee, Yong-Jae;Cha, Dong-Seok;Park, Eun-Young;Kang, Yang-Gyu;Jeon, Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.4
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    • pp.853-859
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    • 2009
  • Nardostachys chinensis has been used widely as a traditional medicine for the treatment of diverse diseases. The dried plant was extracted with 85% methanol extract (NC). We investigated the antioxidant properties of NC on the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, superoxide anion and nitric oxide radical scavenging capacity under in vitro assays. NC showed potent antioxidant activity, compared to ascorbic acid. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was also investigated that the inhibition effects on NO and the mechanism of down-regulation of immune response by NC in IFN-IFN-$\gamma$/LPS-stimulated mouse (C57BL/6) peritoneal macrophages. Extracts of NC suppressed NO production and the expression of iNOS and COX-2. The present results indicate that NC has an antioxidant and anti-inflammatory properties and therefore may be beneficial in diseases which related to oxidative stress-mediated chronic inflammatory disorders.

Current Status of Human Taeniasis in Lao People's Democratic Republic

  • Jeon, Hyeong-Kyu;Yong, Tai-Soon;Sohn, Woon-Mok;Chai, Jong-Yil;Min, Duk-Young;Yun, Cheong-Ha;Rim, Han-Jong;Pongvongsa, Tiengkham;Banouvong, Virasack;Insisiengmay, Bounnaloth;Phommasack, Bounlay;Eom, Keeseon S.
    • Parasites, Hosts and Diseases
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    • v.51 no.2
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    • pp.259-263
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    • 2013
  • Human taeniasis was investigated in Lao People's Democratic Republic (Lao PDR) between 2000 and 2011 as part of the nation's helminthiasis survey. A total of 55,038 inhabitants, including 29,846 school children, were examined using the Kato-Katz and scotch-tape anal swab method, and morphological observation of adult worms. Molecular identification of Taenia tapeworms was performed by multiplex PCR or DNA sequence analysis of the mitochondrial cox1 gene. Taenia eggs were present at a rate of 1.5% (845/55,038) in the subject population. Adult tapeworms were identified as T. solium or T. saginata by analyzing the collectable stool specimens (n=126). Three specimens identified as T. solium were found in Luang Prabang, while the remaining 123 specimens, which were T. saginata, were found in Bokeo, Bolikhamxay, Champasak, Houaphan, Khammouane, Luang Namta, Luang Prabang, Oudomxay, Phongsaly, Saysomboune, Saravane, Savannakhet, Xayaboury, Xekong, Xieng Khouang Province, and Vientiane Municipality.

Preoperative Neutrophil to Lymphocyte Ratio as a Prognostic Factor in Patients with Non-metastatic Renal Cell Carcinoma

  • Wen, Ru-Min;Zhang, Yi-Jing;Ma, Sha;Xu, Ying-Li;Chen, Yan-Su;Li, Hai-Long;Bai, Jin;Zheng, Jun-Nian
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3703-3708
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    • 2015
  • Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

Fitting Cure Rate Model to Breast Cancer Data of Cancer Research Center

  • Baghestani, Ahmad Reza;Zayeri, Farid;Akbari, Mohammad Esmaeil;Shojaee, Leyla;Khadembashi, Naghmeh;Shahmirzalou, Parviz
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7923-7927
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    • 2015
  • Background: The Cox PH model is one of the most significant statistical models in studying survival of patients. But, in the case of patients with long-term survival, it may not be the most appropriate. In such cases, a cure rate model seems more suitable. The purpose of this study was to determine clinical factors associated with cure rate of patients with breast cancer. Materials and Methods: In order to find factors affecting cure rate (response), a non-mixed cure rate model with negative binomial distribution for latent variable was used. Variables selected were recurrence cancer, status for HER2, estrogen receptor (ER) and progesterone receptor (PR), size of tumor, grade of cancer, stage of cancer, type of surgery, age at the diagnosis time and number of removed positive lymph nodes. All analyses were performed using PROC MCMC processes in the SAS 9.2 program. Results: The mean (SD) age of patients was equal to 48.9 (11.1) months. For these patients, 1, 5 and 10-year survival rates were 95, 79 and 50 percent respectively. All of the mentioned variables were effective in cure fraction. Kaplan-Meier curve showed cure model's use competence. Conclusions: Unlike other variables, existence of ER and PR positivity will increase probability of cure in patients. In the present study, Weibull distribution was used for the purpose of analysing survival times. Model fitness with other distributions such as log-N and log-logistic and other distributions for latent variable is recommended.

Associations of Most Prevalent Risk Factors with Lung Cancer and Their Impact on Survival Length

  • Khan, Mohammad Haroon;Hussain, Shahid;Bano, Raisa;Jamshed-ul-Hassan, Hafiz;Aadil ur Rehman, Muhammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.65-70
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    • 2016
  • Lung cancer is one of the most common malignancies in the world. Its incidence and mortality rates are on the rise in Pakistan. However, epidemiological studies to identify common lung cancer determinants in the Pakistani population have been limited. In this study, data of 440 cases and 323 controls were collected from different hospitals in Peshawar and Islamabad, along with information about socio-demographic factors including age, sex and smoking. Univariate and multi-factorial analyses of socio-demographic factors in association with each other were also performed. Overall survival analysis highlighted that, out of 440 patients in the lung cancer dataset, 204 people were uncensored with a median survival time of 13 months (95% CI=12-18). There were 41 femaleand 399 male patients. Differences were observed between length of survival in the males and females (${\chi}12$ = 6.1; p-value = 0.01). Gender was observed to be significantly related to survival (p-value< 0.01), with better survival in females (hazard ratio=2). Cox regression was extended to adjust for the covariate age (z = 2.5; p-value = 0.02). Survival analysis was also performed on the basis of smoking groups (current smokers, former smokers and never smoked individuals) and smoking duration (smoking duration >10 years, <10 years and never smoked). Smoking duration was significantly associated with survival (p-value < 0.01), with better survival in never smokers in comparison to both smoking for greater or less than 10 years. Strong associations were observed for smoking group with duration greater than 10 years, OR=6.1(3.9-9.5) on univariate and multifactorial analysis OR=11.3(CI=6.8-19.3).

Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

  • Lee, Eunjung;Jeong, Ki-Woong;Shin, Areum;Jin, Bonghwan;Jnawali, Hum Nath;Jun, Bong-Hyun;Lee, Jee-Young;Heo, Yong-Seok;Kim, Yangmee
    • BMB Reports
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    • v.46 no.12
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    • pp.594-599
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    • 2013
  • The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-${\alpha}$, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signal-regulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, $8.79{\times}10^5M^{-1}$. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

Screening and Characterization of Lactobacillus casei MCL Strain Exhibiting Immunomodulation Activity

  • Choi, Jae-Kyoung;Lim, Yea-Seul;Kim, Hee-Jin;Hong, Yeong-Ho;Ryu, Buom-Yong;Kim, Geun-Bae
    • Food Science of Animal Resources
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    • v.32 no.5
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    • pp.635-643
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    • 2012
  • As an appraisal for the application of a new starter culture, more than 200 lactic acid bacteria strains were isolated from raw milk and healthy human feces. The strains showing excellent growth and acid production ability in 10% skim milk media were selected and identified as Lactobacillus casei based on the results of their API carbohydrate fermentation patterns, as well as 16S rDNA sequence analysis. To assess the effect of L. casei strains on irritable bowel disease (IBD), the inhibitory effect of the selected strains against the nitric oxide (NO) production of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was measured. Among the tested L. casei strains, L. casei MCL was observed to have the greatest NO inhibitory activity. Additionally, L. casei MCL was found to inhibit mRNA expression of pro-inflammatory cytokines (interleukin-$1{\beta}$, IL-6, TNF-${\alpha}$), as well as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) involved in pathophysiologic processes such as inflammation. The mRNA expression of anti-inflammatory cytokines, including IL-10 and transforming growth factor-$1{\beta}$ (TGF-${\beta}$) of L. casei MCL, was confirmed using quantitative real-time PCR. In conclusion, L. casei MCL showed decreases in the expression of pro-inflammatory cytokines and up-regulated expression of the anti-inflammatory cytokine.

National trends in radiation dose escalation for glioblastoma

  • Wegner, Rodney E.;Abel, Stephen;Horne, Zachary D.;Hasan, Shaakir;Verma, Vivek;Ranjan, Tulika;Williamson, Richard W.;Karlovits, Stephen M.
    • Radiation Oncology Journal
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    • v.37 no.1
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    • pp.13-21
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    • 2019
  • Purpose: Glioblastoma (GBM) carries a high propensity for in-field failure despite trimodality management. Past studies have failed to show outcome improvements with dose-escalation. Herein, we examined trends and outcomes associated with dose-escalation for GBM. Materials and Methods: The National Cancer Database was queried for GBM patients who underwent surgical resection and external-beam radiation with chemotherapy. Patients were excluded if doses were less than 59.4 Gy; dose-escalation referred to doses ≥66 Gy. Odds ratios identified predictors of dose-escalation. Univariable and multivariable Cox regressions determined potential predictors of overall survival (OS). Propensity-adjusted multivariable analysis better accounted for indication biases. Results: Of 33,991 patients, 1,223 patients received dose-escalation. Median dose in the escalation group was 70 Gy (range, 66 to 89.4 Gy). The use of dose-escalation decreased from 8% in 2004 to 2% in 2014. Predictors of escalated dose were African American race, lower comorbidity score, treatment at community centers, decreased income, and more remote treatment year. Median OS was 16.2 months and 15.8 months for the standard and dose-escalated cohorts, respectively (p = 0.35). On multivariable analysis, age >60 years, higher comorbidity score, treatment at community centers, decreased education, lower income, government insurance, Caucasian race, male gender, and more remote year of treatment predicted for worse OS. On propensity-adjusted multivariable analysis, age >60 years, distance from center >12 miles, decreased education, government insurance, and male gender predicted for worse outcome. Conclusion: Dose-escalated radiotherapy for GBM has decreased over time across the United States, in concordance with guidelines and the available evidence. Similarly, this large study did not discern survival improvements with dose-escalation.