• IMMUNE NETWORK
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• 제20권4호
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• pp.33.1-33.19
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• 2020

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both T_H1 and T_H2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces T_H2 and T_H17 responses but reduces T_H1 and T_reg responses regardless of adjuvant type, whereas CFA but not alum increased follicular T_H response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

• Parasites, Hosts and Diseases
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• 제30권3호
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• pp.177-182
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• 1992

Saimiri 원숭이 21마리와 Aotus 원숭이 12마리에게 Plasmedium falciparum Indochina CDC-1충주(원숭이 순응 충주)를 접종시킨 후 3주간 혈소판과 혈액치를 경시적으로 관찰하였던 바, 이들 원숭이 (Saimiri sciureus boliviensis와 Aotus nancymai karyotype-1)는 접종 14일 후에 최고의 기생률, 호중구감소증, 임파구증가증 그리고 심한 혈색소혈증과 섬유소원의 퇴행성 산물(FDP's)치의 증가를 수반한 섬한 혈소판 감소성 빈혈증이 관찰되었다. Aotus에 있어서는 평균혈색소량(MCH)과 평균혈구용적(MCV)치의 감소와 기생률의 증가를 가져왔으나, Saimiri에 있어서는 기생률이 상승함에 따라서 이들 혈액치는 유의적 차이로 상승하는 결과를 가져왔다. 일반적으로 이들 두 원숭이에 있어서 혈소판의 감소 증세와 최고 기생률을 14잎 째 나타낸 후 곧 정상 혈액치로 회복되는 소견이 관찰된다. 특히 혈소판의 변화에 있어서 Aotus 원숭이는 다른 혈액치의 변화 그리고 기생률과 깊 은 상관관계를 갖고 있었으나, Saimiri에 있어서는 상관관계를 유지하지 못하였다. 결론적으로 말라리아 연구시 Aotus 원숭이가 Saimiri 원숭이 보다 우수한 품종임과 말라리아 진단과정에 있어서 혈소판의 회복률과 재생은 말라리아의 감염시기 판정에 유용한 자료로서 활용될 수 있음을 관찰하였으며, 말라리아 병원성 판정에 대한 실험에 있어서 이들 두 종류 원숭이의 혈액치 변화 특이성을 보고하는 바이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• 한국동물위생학회지
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• 제42권4호
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• pp.193-200
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• 2019

Blood test is a useful tool in establishing medical treatment for livestock. It provides information such as disease diagnosis, treatment effects, prognostic judgment, and health status. This study compared the value of erythrocytes and leukocytes among conventional, transgenic miniature, and transgenic conventional pigs aged six months to 24 months. Further, it analyzed the aspects of hematological value changes according to the pigs' ages. As a result, the number of red blood cells (RBC), which include hemoglobin, and hematocrit, and the number of white blood cells (WBC), which include neutrophils, and lymphocyte, were high among transgenic miniature pigs, compared with the conventional and transgenic conventional pigs. Conventional pigs showed similar values of RBC and WBC regardless of transgenesis. In comparing their age, the RBC decreased as the age increased compared with the pigs among all the three groups aged of 6~12 months. On the other hand, WBC and neutrophils showed no significant difference regardless of different ages among all the three groups. However, various counts in RBC and WBC were mostly found to be higher in each age in transgenic miniature pigs than in conventional and transgenic conventional pigs. The results of this study show that the values of RBC and WBC were generally higher in transgenic miniature pigs than in conventional and transgenic conventional pigs. Based on this research, hematological values can be widely used in diagnosing diseases or checking the health status of transgenic pigs that are used as disease models, organ transplant source and alike.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6111-6116
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• 2015

Background: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. Materials and Methods: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. Results: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. Conclusions: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

• Journal of Trauma and Injury
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• 제34권1호
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• pp.3-12
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• 2021

Purpose: To evaluate the severity of trauma, many scoring systems and predictive models have been presented. The quick Sequential Organ Failure Assessment (qSOFA) is a simple scoring system based on vital signs, and we expect it to be easier to apply to trauma patients than other trauma assessment tools. Methods: This study was a cross-sectional study of trauma patients who visited the emergency department of Jeju National University Hospital. We excluded patients under the age of 18 years and unknown outcomes. We calculated the qSOFA, the Modified Early Warning Score (mEWS), Revised Trauma Score (RTS), and Injury Severity Score (ISS) based on patients' initial vital signs and assessments performed in the emergency department (ED). The primary outcome was mortality within 14 days of trauma. We analyzed qSOFA scores using multivariate logistic regression analysis and compared the predictive accuracy of these scoring systems using the area under the receiver operating characteristic curve (AUROC). Results: In total, 27,764 patients were analyzed. In the multivariate logistic regression analysis of the qSOFA, the adjusted odds ratios with 95% confidence interval (CI) for mortality relative to a qSOFA score of 0 were 27.82 (13.63-56.79) for a qSOFA score of 1, 373.31 (183.47-759.57) for a qSOFA score of 2, and 494.07 (143.75-1698.15) for a qSOFA score of 3. In the receiver operating characteristic (ROC) curve analysis for the qSOFA, mEWS, ISS, and RTS in predicting the outcomes, for mortality, the AUROC for the qSOFA (AUROC [95% CI]; 0.912 [0.871-0.952]) was significantly greater than those for the ISS (0.700 [0.608-0.793]) and RTS (0.160 [0.108-0.211]). Conclusions: The qSOFA was useful for predicting the prognosis of trauma patients evaluated in the ED.

• 대한한의학방제학회지
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• 제31권3호
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

• Korean Journal of Radiology
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• 제24권5호
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• pp.434-443
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• 2023

Objective: To investigate the association between pelvic bone computed tomography (CT)-derived body composition and patient outcomes in older adult patients who underwent surgery for proximal femur fractures. Materials and Methods: We retrospectively identified consecutive patients aged ≥ 65 years who underwent pelvic bone CT and subsequent surgery for proximal femur fractures between July 2018 and September 2021. Eight CT metrics were calculated from the cross-sectional area and attenuation of the subcutaneous fat and muscle, including the thigh subcutaneous fat (TSF) index, TSF attenuation, thigh muscle (TM) index, TM attenuation, gluteus maximus (GM) index, GM attenuation, gluteus medius and minimus (Gmm) index, and Gmm attenuation. The patients were dichotomized using the median value of each metric. Multivariable Cox regression and logistic regression models were used to determine the association between CT metrics with overall survival (OS) and postsurgical intensive care unit (ICU) admission, respectively. Results: A total of 372 patients (median age, 80.5 years; interquartile range, 76.0-85.0 years; 285 females) were included. TSF attenuation above the median (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.41-4.05), GM index below the median (adjusted HR, 2.63; 95% CI, 1.33-5.26), and Gmm index below the median (adjusted HR, 2.33; 95% CI, 1.12-4.55) were independently associated with shorter OS. TSF index (adjusted odds ratio [OR], 6.67; 95% CI, 3.13-14.29), GM index (adjusted OR, 3.45; 95% CI, 1.49-7.69), GM attenuation (adjusted OR, 2.33; 95% CI, 1.02-5.56), Gmm index (adjusted OR, 2.70; 95% CI, 1.22-5.88), and Gmm attenuation (adjusted OR, 2.22; 95% CI, 1.01-5.00) below the median were independently associated with ICU admission. Conclusion: In older adult patients who underwent surgery for proximal femur fracture, low muscle indices of the GM and gluteus medius/minimus obtained from their cross-sectional areas on preoperative pelvic bone CT were significant prognostic markers for predicting high mortality and postsurgical ICU admission.

• Korean Journal of Radiology
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• 제23권12호
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• pp.1269-1280
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• 2022

Objective: This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD). Materials and Methods: We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters. Results: Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11-117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ΔLS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ΔLS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023). Conclusion: MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.

• Korean Journal of Radiology
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• 제22권12호
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• pp.1985-1995
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• 2021

Objective: Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis. Materials and Methods: A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007-2010). Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator. Results: After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B-C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications. Conclusion: The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.