• Journal of Ginseng Research
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• v.44 no.4
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• pp.593-602
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• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.471-479
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• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.69-76
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• 1992

To identify pretreatment prognostic factors in locally advanced carcinoma of the uterine cervix, retrospective analysis was undertaken of 154 patients treated with curative radiation therapy at Seoul National University Hospital, from March 1979 through December 1986. According to FIGO classification, eight patients were stage IIIA, 134 were stage IIIB, and 12 were stage IVA. Five year locoregional control rate was $58\%$, $51\%$, and $27\%$ in stage IIIA, IIIB, and IVA, respectively. Five year disease free survival was $57\%$, $40\%$, and $25\%$ for each stage respectively. Five year overall survival was $67\%$, $51\%$, and $33\%$ in stage IIIA, IIIB, and IVA, respectively. In univariate analysis, fewer than or equal to four of pregnancies, initial hemoglobin of lower than $10\;g\%$, and pelvic sidewall invasion on CT were associated with poor locoregional control. Number of pregnancies, initial hemoglobin level, obstructive uropathy on intavenous pyelography (IVP), pelvic lymph node (LN) status on CT, and pelvic sidewall invasion on CT were significant factors in disease free survival. In terms of overall survival, pelvic sidewall invasion on CT and bladder invasion on CT were prognostically significant. In multivariate analysis, no factor was found to affect locoregional control and pelvic LN status was a sole significant factor affecting disease free survival. in terms of overall survival, the size.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.610-614
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• 2009

Background: Several trials have reported on whether adjuvant chemotherapy for resected stage IB non-small cell lung cancer is needed. The aim of our study was to investigate prognostic factors for recurrence to help identify patients who should receive adjuvant chemotherapy. Material and Method: We reviewed the cases of 48 stage IB non-small cell lung cancer patients between 1997 and 2006. Disease-free survival and overall survival rates were calculated by the Kaplan-Meier method. Univariate analysis was performed with the log rank test and multivariate analysis was done using Cox's proportional hazard model. Result: The median follow-up time was 48 months. The overall survival rate was 55.9%, and the disease-free survival rate was 48.6%. Of 8 variables, two factors, visceral pleural invasion and Iymphovascular invasion, were prognostic factors of disease-free survival (univariate analysis). Visceral pleural invasion was a significant prognostic factor in multivariate analysis, and overall survival in com-pared one or more variable such as visceral pleural invasion or, and lymphovascular invasion with the other variables. Conclusion: Visceral pleural invasion was identified as a poor prognostic factor and it may help select which patients will benefit from adjuvant chemotherapy in addition to more comprehensive follow-up.

• Journal of Chest Surgery
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• v.40 no.10
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• pp.680-684
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• 2007

Background: Complete surgical resection is the most effective treatment for stage IB non-small cell lung cancer (NSCLC). Recurrence accounts for the disappointing survival rates after resection. There has been renewed interest in adjuvant therapy after complete resection. Appropriate selection of effective adjuvant therapy will depend on the prognostic factors for recurrence. Material and Method: The study included 114 patients with completely resected stage IB NSCLC. The variables selected for the study were gender, age, the type of resection, cell type, the degree of differentiation, the tumor size and the presence of visceral pleura invasion. The Kaplan-Meier method was used to estimate the survival and disease-free survival rate. The results were compared using the log rank test. Multivariate analysis was performed by Cox's proportional hazard model. Two-sided p-valves < 0.05 were considered to be statistically significant. Result: The 3-year overall survival and the disease-free survival rates were 87.0% and 79.4%, respectively. The degree of differentiation showed a significant influence on disease-free survival according to the univariate analysis. According to the multivariate analysis, a poor grade of differentiation was a significant poor prognostic factor. Conclusion: These results demonstrate that poor differentiation may be a poor prognostic factor for patients with completely resected IB NSCLC. Therefore, the patients with a poor grade of differentiation may require adjuvant therapies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4739-4743
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• 2012

Background: Predictive biomarkers for lung cancer recurrence after curative tumor resection remain unclear. This study set out to assess the role of FoxM1 in the recurrence of non-small cell lung cancer. Methods: Immunohistochemistry for FoxM1 expression was performed on paraffin-embedded tumor tissues from 165 NSCLC patients. Association of FoxM1 expression with clinicopathological parameters and disease free survival were evaluated. Results: Our results indicated FoxM1 expression to be significantly associated with poorer tissue differentiation (P =0.03), higher TNM stage (P <0.01), lymph node metastasis (P <0.01), advanced tumor stage (P <0.01), and poorer disease free survival (P <0.01). Multivariable analysis showed that FoxM1 expression increased the hazard of recurrence (hazard ratio= 1.96, 95% CI, 1.04-3.17, P <0.05), indicating that FoxM1 is an independent and significant predictor of lung cancer recurrence. Conclusion: Therefore, FoxM1 is an independent risk factor for recurrence of NSCLC. Elevated FoxM1 expression could be used as an indicator of poor disease free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8101-8105
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• 2014

Background: Although mucinous adenocarcinoma has been recognized for a long time, whether it is associated with a poorer prognosis in colorectal cancer patients is still controversial. Many studies put emphasis on mucinous adenocarcinoma containing mucin component ${\geq}50%$. Only a few studies have analyzed cases with a mucin component <50%. Objectives: This study aimed to analyze the prognostic value of different mucin component proportions in patients with stage III rectal cancer. Materials and Methods: Clinical, pathological and follow-up data of 136 patients with the stage III rectal cancer were collected. Every variable was analyzed by univariate analysis, then multivariate analysis and survival analysis were further performed. Results: Univariate analysis showed pathologic T stage, lymphovascular invasion, and histological subtype were statistically significant for DFS. Pathologic T stage was significant for OS. Histological subtype and lymphovascular invasion were independent prognostic factors in multivariate analysis for DFS, and histological subtype was the only independent prognostic factor for OS. Survival curves showed the survival time of mucinous adenocarcinoma (MUC) was shorter than non-MUC (adenocarcinomas with a mucin component <50% and without mucin component). Conclusions: Histological subtype (tumor with different mucin component) was an independent prognostic factor for both DFS and OS. Patients with MUC had a worse prognosis than their non-MUC counterparts with stage III rectal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.347-352
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• 2016

Background: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) adenosquamous carcinoma data to identify predictive models and potential disparities in outcome. Materials and Methods: This study analyzed socio-economic, staging and treatment factors available in the SEER database for adenosquamous carcinoma. For the risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. An area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. Results: A total of 20,712 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 54.2 (78.4) months. Some 2/3 of the patients were female. The mean (S.D.) age was 63 (13.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.71). 13.9% of the patients were un-staged and had risk of cause specific death of 61.3% that was higher than the 45.3% risk for the regional disease and lower than the 70.3% for metastatic disease. Sex, site, radiotherapy, and surgery had ROC areas of about 0.55-0.65. Rural residence and race contributed to socioeconomic disparity for treatment outcome. Radiotherapy was underused even with localized and regional stages when the intent was curative. This under use was most pronounced in older patients. Conclusions: Anatomic stage was predictive and useful in treatment selection. Under-staging may have contributed to poor outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.353-356
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• 2016

Background: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) for glassy cell carcinoma data to identify predictive models and potential disparities in outcome. Materials and Methods: This study analyzed socio-economic, staging and treatment factors. For risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. Area under the receiver operating characteristic curves (ROCs) were computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate modeling errors. Risk of glassy cell carcinoma death was computed for the predictors for comparison. Results: There were 79 patients included in this study. The mean follow up time (S.D.) was 37 (32.8) months. Female patients outnumbered males 4:1. The mean (S.D.) age was 54.4 (19.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.69). The risks of cause specific death were, respectively, 9.4% for localized, 16.7% for regional, 35% for the un-staged/others category, and 60% for distant disease. After optimization, separation between the regional and unstaged/others category was removed with a higher ROC area of 0.72. Several socio-economic factors had small but measurable effects on outcome. Radiotherapy had not been used in 90% of patients with regional disease. Conclusions: Optimized SEER stage was predictive and useful in treatment selection. Underuse of radiotherapy may have contributed to poor outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.175-179
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• 2015

Rad51, a key factor in the homologous recombination pathway for the DNA double-strand break repair, plays a vital role in genesis of non-small-cell lung cancer (NSCLC). In recent years, more and more studies indicate that high expression of Rad51 is of great relevance to resistance of NSCLC to chemotherapeutic agents and ionizing radiation. However, the underlying molecular mechanisms are poorly understood. In this study, we investigated the role of single Rad51 on cell viability in vitro. Our results show that depletion of endogenous Rad51 is sufficient to inhibit the growth of the A549 lung cancer cell line, by accumulating cells in G1 phase and inducing cell death. We conclude that independent Rad51 expression is critical to the survival of A549 cells and can be an independent prognostic factor in NSCLC patients.