• Journal of Applied Biological Chemistry
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• v.66
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• pp.53-59
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• 2023

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has no effect on normal cells, but selectively can induce apoptosis in tumor cells. Gartanin, a xanthone compound in mangosteen, has been shown to inhibit cancer cell growth by arresting the cell cycle and inducing autophage. In this study, we revealed that gartanin can sensitize TRAIL-induced human liver cancer cell death. We also found that gartanin enhances DR5 expression, a death receptor for TRAIL. This effect appears to be related to CHOP activation associated with the response of endoplasmic reticulum stress. Gartanin treatment also inhibited p62 protein expression and cleaved LC3 to activate autophagy flux, which is related with TRAIL-induced cell death. Pretreatment with autophagy flux inhibitor, LY294002, inhibited gartanin-induced DR5 expression. In summary, our results reveal that the combined treatment of gartanin and TRAIL can be a valuable tool for cancer treatment.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.3
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• pp.169-175
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• 2022

Bovine mammary epithelial (MAC-T) cells are commonly used to study mammary gland development and mastitis. Lipopolysaccharide is a major bacterial cell membrane component that can induce inflammation. Autophagy is an important regulatory mechanism participating in the elimination of invading pathogens. In this study, we evaluated the mechanism underlying bacterial mastitis and mammary cell death following lipopolysaccharide treatment. After 24 h of 50 ㎍/mL lipopolysaccharide treatment, a significant decrease in the proliferation rate of MAC-T cells was observed. However, no changes were observed upon treatment of MAC-T cells with 10 ㎍/mL of lipopolysaccharide for up to 48 h. Thus, upon lipopolysaccharide treatment, MAC-T cells exhibit dose-dependent effects of growth inhibition at 10 ㎍/mL and death at 50 ㎍/mL. Treatment of MAC-T cells with 50 ㎍/mL lipopolysaccharide also induced the expression of autophagy-related genes ATG3, ATG5, ATG10, ATG12, MAP1LC3B, GABARAP-L2, and BECN1. The autophagy-related LC3A/B protein was also expressed in a dose-dependent manner upon lipopolysaccharide treatment. Based on these results, we suggest that a high dose of bacterial infection induces mammary epithelial cell death related to autophagy signals.

• Journal of Korean Neurosurgical Society
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• v.59 no.5
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• pp.485-491
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• 2016

Objective : The aims of the Korean Neuro-Trauma Data Bank System (KNTDBS) are to evaluate and improve treatment outcomes for brain trauma, prevent trauma, and provide data for research. Our purpose was to examine the mortality rates following traumatic brain injury (TBI) in a retrospective study and to investigate the sociodemographic variables, characteristics, and causes of TBI-related death based on data from the KNTDBS. Methods : From 2010 to 2014, we analyzed the data of 2617 patients registered in the KNTDBS. The demographic characteristics of patients with TBI were investigated. We divided patients into 2 groups, survivors and nonsurvivors, and compared variables between the groups to investigate variables that are related to death after TBI. We also analyzed variables related to the interval between TBI and death, mortality by region, and cause of death in the nonsurvivor group. Results : The frequency of TBI in men was higher than that in women. With increasing age of the patients, the incidence of TBI also increased. Among 2617 patients, 688 patients (26.2%) underwent surgical treatment and 125 patients (4.7%) died. The age distributions of survivors vs. nonsurvivor groups and mortality rates according the severity of the brain injury, surgical treatment, and initial Glasgow Coma Scale (GCS) scores were statistically significantly different. Among 125 hospitalized nonsurvivors, 70 patients (56%) died within 7 days and direct brain damage was the most common cause of death (80.8%). The time interval from TBI to death differed depending on the diagnosis, surgical or nonsurgical treatment, severity of brain injury, initial GCS score, and cause of death, and this difference was statistically significant. Conclusion : Using the KNTDBS, we identified epidemiology, mortality, and various factors related to nonsurvival. Building on our study, we should make a conscious effort to increase the survival duration and provide rapid and adequate treatment for TBI patients.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.308-317
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• 2021

Cancer is the leading cause of death and is on the rise worldwide. Until 2010, the development of targeted treatment was mainly focused on the growth mechanisms of cancer. Since then, drugs with mechanisms related to tumor immunity, especially immune checkpoint inhibitors, have proven effective, and most pharmaceutical companies are striving to develop related drugs. Programmed cell death-1 and programmed cell death ligand-1 inhibitors have shown great success in various cancer types. They showed durable and sustainable responses and were approved by the U.S. Food and Drug Administration. However, the response to inhibitors showed low percentages of cancer patients; 15% to 20%. Therefore, combination strategies with immunotherapy and conventional treatments were used to overcome the low response rate. Studies on combination therapy have typically reported improvements in the response rate and efficacy in several cancers, including non-small cell lung cancer, small cell lung cancer, breast cancer, and urogenital cancers. The combination of chemotherapy or targeted agents with immunotherapy is one of the leading pathways for cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1449-1453
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• 2015

Background: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from $1^{st}$ January 2009 till $31^{st}$ June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. Results: Between $1^{st}$ January 2009 and $30^{th}$ June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. Conclusions: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.

• The Korean journal of internal medicine
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• v.39 no.4
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• pp.640-649
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• 2024

Background/Aims: This study aimed to investigate the timing and predictors of death during treatment among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB) in South Korea. Methods: This was a retrospective cohort study that included MDR/RR-TB cases notified between 2011 and 2017 in South Korea. Results: Among 7,226 MDR/RR-TB cases, 699 (9.7%) died at a median of 167 days (IQR 51-358 d) from the initiation of MDR-TB treatment. The cumulative proportion of all-cause death was 35.5% at 90 days and 52.8% at 180 days from treatment initiation. TB-related deaths occurred at a median of 133 days (IQR 32-366 d), which was significantly earlier than the median of 184 days (IQR 68-356 d) for non-TB-related deaths (p = 0.002). In a multivariate analysis, older age was the factor most strongly associated with death, with those aged ≥ 75 years being 68 times more likely to die (aHR 68.11, 95% CI 21.75-213.26), compared those aged ≤ 24 years. In addition, male sex, comorbidities (cancer, human immunodeficiency virus, and end stage renal disease), the lowest household income class, and TB-specific factors (previous history of TB treatment, smear positivity, and fluoroquinolone resistance) were identified as independent predictors of all-cause death. Conclusions: This nationwide study highlights increased deaths during the intensive phase and identifies high-risk groups including older people and those with comorbidities or socioeconomic vulnerabilities. An integrated and comprehensive strategy is required to reduce mortality in patients with MDR/RR-TB, particularly focusing on the early stages of treatment and target populations.

• Journal of Hospice and Palliative Care
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• v.26 no.2
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• pp.80-94
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• 2023

Purpose: This study aimed to identify attitudes toward advance directives (ADs) among female cancer patients and factors related to ADs. Methods: The study was conducted at a university hospital in Seoul from September 19, 2020, to January 20, 2021. The participants were 153 patients diagnosed with gynecological cancer or breast cancer. Data were collected using questionnaires and included general characteristics, disease- and AD-related characteristics, knowledge and attitudes about ADs, and attitudes about dignified death. Data were analyzed using the t-test, analysis of variance, and multiple regression analysis. Results: Only 2% of the participants completed ADs. The mean score for attitudes toward ADs was 3.30, indicating a positive knowledge and attitude toward dignified death. The factors related to attitudes toward ADs were attitudes toward dignified death (𝛽=0.25, P=0.001), experience discussing life-sustaining treatment (𝛽=0.17, P=0.037), preferred time to have a consultation about ADs (𝛽=0.19, P=0.046), intention to write ADs (𝛽=0.15, P=0.038), and Eastern Cooperative Oncology Group Performance Status (𝛽=-0.37, P<0.001). The explanatory power of these variables for attitudes toward ADs was 38.5%. Conclusion: Overall, patients preferred to have a consultation about ADs when they were still active, mentally healthy, and able to make decisions. Education about ADs should be provided to patients on the first day of hospitalization for chemotherapy or while awaiting treatment in an outpatient setting so patients can write ADs and discuss them with family and friends.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4623-4626
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• 2012

Background: The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane-based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). Patients and Methods: Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$. Results: A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. Conclusion: Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

• The Journal of Korean Academic Society of Nursing Education
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• v.26 no.4
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• pp.383-392
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• 2020

Purpose: This study was a descriptive study to identify factors affecting the attitude toward life-sustaining treatment of nurses working at long-term care hospitals. Methods: Data were collected through structured questionnaires from August 2nd to 27th, 2019. Study participants consisted of 163 nurses who were working for at least 6 months from 7 long-term care hospitals in B and K city. Data were analyzed using t-test, ANOVA, Scheffe' test, Pearson's correlation coefficients, and hierarchical regression with SPSS WIN v 21.0. Results: There were significantly positive correlations between awareness of good death (r=.46, p<.001) and perception of patients' rights (r=.32, p<.001). The factors affecting participants' attitude toward life-sustaining treatment were awareness of good death (β=.35, p<.001) and their own view of death (β=.24, p=.001), which explained about 27.0% of the attitude toward life-sustaining treatment. Conclusion: Based on these results, it is necessary to develop nursing educational materials that can establish values for deaths, and cultivate legal and ethical knowledge related to attitude toward life-sustaining treatment. In addition, since the severity of a patient's condition varies and the characteristics of the institution vary depending on the type of hospital, a study is needed on the relevance of variables considering the hospital environment.

• Journal of Trauma and Injury
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• v.34 no.4
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• pp.225-232
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• 2021

Purpose: Trauma is the top cause of death in people under 45 years of age. Deaths from severe trauma can have a negative economic impact due to the loss of people belonging to socio-economically active age groups. Therefore, efforts to reduce the mortality rate of trauma patients are essential. The purpose of this study was to investigate preventable mortality in trauma patients and to identify factors and healthcare-related challenges affecting mortality. Ultimately, these findings will help to improve the quality of trauma care. Methods: We analyzed the deaths of 411 severe trauma patients who presented to Gachon University Gil Hospital regional trauma center in South Korea from January 2015 to December 2017, using an expert panel review. Results: The preventable death rate of trauma patients treated at the Gachon University Gil Hospital regional trauma center was 8.0%. Of these, definitely preventable deaths comprised 0.5% and potentially preventable deaths 7.5%. The leading cause of death in trauma patients was traumatic brain injury. Treatment errors most commonly occurred in the intensive care unit (ICU). The most frequent management error was delayed treatment of bleeding. Conclusions: Most errors in the treatment of trauma patients occurred in early stages of the treatment process and in the ICU. By identifying the main causes of preventable death and errors during the course of treatment, our research will help to reduce the preventable death rate. Appropriate trauma care systems and ongoing education are also needed to reduce preventable deaths from trauma.