• The Korean journal of internal medicine
• /
• v.39 no.3
• /
• pp.501-512
• /
• 2024

Background/Aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL). Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS). Results: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%. Conclusions: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

• Korean Journal of Radiology
• /
• v.25 no.7
• /
• pp.644-655
• /
• 2024

Objective: To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine18-fluorodeoxyglucose (¹⁸F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage. Results: A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on ¹⁸F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17). Conclusion: The proposed risk score based on preoperative CA 19-9, CT, and ¹⁸F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.

• Korean Journal of Radiology
• /
• v.25 no.8
• /
• pp.715-725
• /
• 2024

Objective: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-㎛ doxorubicin DEBs (group A), and 103 patients received 100-300-㎛ doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. Results: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). Conclusion: DEB-TACE using 70-150-㎛ microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-㎛).

• Annals of Occupational and Environmental Medicine
• /
• v.34
• /
• pp.4.1-4.11
• /
• 2022

Background: Long working hours are known to account for approximately one-third of the total expected work-related diseases, and much interest and research on long working hours have recently been conducted. Additionally, as the prevalence of prediabetes and the high-risk group for diabetes are increasing worldwide, interest in prediabetes is also rising. However, few studies have addressed the development of type 2 diabetes and long working hours in prediabetes. Therefore, the aim of this longitudinal study was to evaluate the relationship between long working hours and the development of diabetes in prediabetes. Methods: We included 14,258 prediabetes participants with hemoglobinA1c (HbA1c) level of 5.7 to 6.4 in the Kangbuk Samsung Cohort Study. According to a self-reported questionnaire, we evaluated weekly working hours, which were categorized into 35-40, 41-52, and > 52 hours. Development of diabetes was defined as an HbA1c level ≥ 6.5%. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of diabetes were estimated using Cox proportional hazards analyses with weekly working 35-40 hours as the reference. Results: During a median follow-up of 3.0 years, 776 participants developed diabetes (incidence density, 1.66 per 100 person-years). Multivariable-adjusted HRs of development of diabetes for weekly working > 52 hours compared with working 35-40 hours were 2.00 (95% CI: 1.50-2.67). In subgroup analyses by age (< 40 years old, ≥ 40 years old), sex (men, women), and household income (< 6 million KRW, ≥ 6 million KRW), consistent and significant positive associations were observed in all groups. Conclusions: In our large-scale longitudinal study, long working hours increases the risk of developing diabetes in prediabetes patients.

• Journal of Chest Surgery
• /
• v.36 no.7
• /
• pp.489-496
• /
• 2003

To clarify the prognostic implication of the location and number of the metastatic mediastinal nodes in resected stage IIIA N2 non-small cell lung cancer. Material and Method: One hundred and seventy-four patients with resected non-small cell lung cancer who eventually proved to have pathologic stage IIIA N2 disease were studied. Patients who received preoperative induction therapy, non-curative operation or defined as operative mortality were excluded from this study. Result: In upper lobe tumors, there was no difference in 5-year survival according to the involvement of lower mediastinal nodes (32.3% vs 25.6%, p＝0.86). In lower lobe tumors, no difference was found in 5-year survival according to the involvement of upper mediastinal nodes (25.1% vs 14.1%, p＝0.33). There was no significant difference in 5-year survival between patients with or without metastatic subcarinal node (20.9% vs 25.6%, p＝0.364). In terms of the number of metastatic mediastinal nodes, 5-year survival was better in single station group (26.3%) than multiple station group (18.3%) (p＝0.048). In multiple station N2 group, the patients who received postoperative chemotherapy and radiation therapy had better 5-year survival (34.2%) (p＝0.01). Cox's proportional hazards model revealed that the age $\geq$60 (O.R: 1.682, p＝.006), multiple station N2 (O.R: 1.503. p＝0.021), pneumonectomy (O.R: 1.562, p＝0.018), postoperative chemotherapy and radiation therapy (O.R: 0.625, p＝0.012) were the factors affecting the postoperative survival. Conclusion: Multiple station N2 disease was the important prognostic factor for postoperative survival in resected stage IIIA N2 non-small cell lung cancer. Postoperative chemotherapy and radiotherapy were thought to improve the survival in case of multiple station N2 disease.

• The Korea Journal of Herbology
• /
• v.29 no.6
• /
• pp.117-123
• /
• 2014

Objectives : Sinhyowoldo-san (SHWDS) is said to be a traditional medicine used for shigellosis, abdominal pain, diarrhea. But mechanism of SHWDS mediated-modulation of immune function is not sufficiently understood. To ascertain the molecular mechanisms of SHWDS 70% EtOH extract on pharmacological and biochemical actions in inflammation, we researched the effect of pro-inflammatory mediators in phorbol-12-myristate-13-acetate (PMA)+ A23187-activated human mast cell line (HMC-1). Methods : In the present research, cell viability was measured by MTS assay. pro-inflammatory cytokine production was measured by performing enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), and western blot analysis to analyze the activation of mitogen-activated protein kinases (MAPKs), nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). The investigation focused on whether SHWDS inhibited the expressions of interleukin-6 (IL-6), interleukin-8 (IL-8), MAPKs and $NF-{\kappa}B$ in PMA+A23187-activated HMC-1 cells. Results : SHWDS has no cytotoxicity at measured concentration (50, 100, and $250{\mu}g/ml$). SHWDS ($250{\mu}g/ml$) inhibits pro-inflammatory cytokine expression in PMA+ A23187-activated HMC-1 cells. Moreover, SHWDS inhibited cyclooxygenase (COX)-2 expression. In activated HMC-1 cells, SHWDS suppressed phosphorylation of extracellular signal-regulated kinase (ERK 1/2) and c-jun N-terminal Kinase (JNK 1/2). Then, SHWDS suppressed activation of nuclear factor $NF-{\kappa}B$ in nuclear, degradation of IkB ${\alpha}$ in cytoplasm. Conclusions : We propose that SHWDS has an anti-inflammatory therapeutic potential, which may result from inhibition of ERK 1/2, JNK 1/2 phosphorylation and $NF-{\kappa}B$ activation, thereby decreasing the expression of pro-inflammatory genes.

• Journal of Life Science
• /
• v.30 no.9
• /
• pp.804-812
• /
• 2020

The giant mealworm beetle, Zophobas atratus (Coleoptera: Tenebrionidae) has been used as a protein source for small pets and mammals. Recently, it was temporarily registered in the list of the Food Code. We previously performed an in silico analysis of the Zophobas atratus transcriptome to identify putative antimicrobial peptides and identified several antimicrobial peptide candidates. Among them, we assessed the antimicrobial and anti-inflammatory activities of zophobacin 1 that was selected bio-informatically based on its physicochemical properties against microorganisms and mouse macrophage Raw264.7 cells. Zophobacin 1 showed antimicrobial activities against microorganisms without inducing hemolysis and decreased the nitric oxide production of the lipopolysaccharide-induced Raw264.7 cells. Moreover, ELISA and Western blot analysis revealed that zophobacin 1 reduced expression levels of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We also investigated expression of pro-inflammatory cytokines (interleukin-6 and interleukin-1β) production through quantitative real time-PCR and ELISA. Zophobacin 1 markedly reduced the expression level of cytokines through the regulation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling. We confirmed that zophobacin 1 bound to bacterial cell membranes via a specific interaction with lipopolysaccharides. These data suggest that zophobacin 1 could be promising molecules for development as antimicrobial and anti-inflammatory therapeutic agents.

• Journal of Life Science
• /
• v.28 no.2
• /
• pp.207-215
• /
• 2018

Inflammatory response and oxidative stress play critical roles in the development and progression of many human diseases. Therefore, a great deal of attention has been focused on finding functional materials that can control inflammation and oxidative stress simultaneously. The purpose of this study was to investigate the effects of Socheongja and Socheong 2, Korean black seed coat soybean varieties, on the inflammatory and oxidative stress induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages. Our data indicated that the extracts of Socheongja (SCJ) and Socheong 2 (SC2) significantly suppressed LPS-induced production of nitrite oxide (NO) and prostaglandin $E_2$, key pro-inflammatory mediators, by suppressing the expression of inducible NO synthase and cyclooxygenase-2. It was also found that SCJ and SC2 reduced the LPS-induced secretion of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$, which was concomitant with a decrease in the protein levels. In addition, SCJ and SC2 markedly diminished LPS-stimulated intracellular reactive oxygen species accumulation, and effectively enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1 expression. Furthermore, LPS-induced activation of mitogen-activated protein kinases (MAPKs) was abrogated by SCJ and SC2. Taken together, these data suggest that SCJ and SC2 may offer protective roles against LPS-induced inflammatory and oxidative responses in RAW 264.7 macrophages through attenuating MAPKs pathway, and these effects are mediated, at least in part, through activating Nrf2/HO-1 pathway. Given these results, we propose that SCJ and SC2 have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by over-activation of macrophages.

• Journal of Applied Biological Chemistry
• /
• v.59 no.3
• /
• pp.179-188
• /
• 2016

This study is aimed to evaluate the protective effect of Gastrodiae rhizoma and steamed, dried & fermented Gastrodiae rhizoma on Lipopolysaccharide (LPS)-induced hepatic injury in the mice model. Sample was selected to GR0F0 (not processed gastrodia rhizome) and GR6F4 (fermented with Saccharomyces cerevisiae before steamed and dried 6 times) based on 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid, and High-performance liquid chromatography analysis. Mice were randomly divided into 4 groups - Normal group, vehicle group (LPS treated), GR0F0 group (fed GR0F0 before LPS treated) and GR6F4 group (fed GR6F4 before LPS treated) with 6 mice in each group. GR0F0 group and GR6F4 group were fed each extract 200 mg/kg/day during 8 days. LPS 20 mg/kg injected to the experimental groups as abdominal injection. We measured aspartate aminotransferase, alanine amino-transferase in serum. GR0F0 and GR6F4 showed a significant decrease compared to the vehicle group. As a result of measuring the ROS, GR6F4 group showed a significant reduction in both the serum and liver tissues compared to the vehicle group. GR0F0 group showed a significant reduction only in the liver tissues. Activator protein-1, cyclooxygenase-2, and Inducible nitric oxide synthase were significantly decreased GR0F0 group and GR6F4 group. But tumor necrosis factor alpha only showed a significant reduction in GR6F4 group. GR0F0 and GR6F4 groups against liver damage in mice with LPS. That showed significant effects on anti-oxidant and anti-inflammatory action. The effects of GR6F4 group showed superior results compared to GR0F0 group. Therefore, Steamed, dried & fermented Gastrodia rhizoma was might have a protective effect on liver injury.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.46 no.6
• /
• pp.659-670
• /
• 2017

Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury.