• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.273-280
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• 2021

Lung cancer despite advancement in the medical field continues to be a major threat to human lives and accounts for a high proportion of fatalities caused by cancers globally. The current study investigated vanillin oxime, a derivative of vanillin, against lung cancer cells for development of treatment and explored the mechanism. Cell viability changes by vanillin oxime were measured using MTT assay. Vanillin oxime-mediated apoptosis was detected in A549 and NCI-H2170 cells at 48 h of exposure by flow cytometry. The CEBP homologous protein (CHOP) and death receptor 5 (DR5) levels were analysed by RT-PCR and protein levels by Western blotting. Vanillin oxime in concentration-dependent way suppressed A549 and NCI-H2170 cell viabilities. On exposure to 12.5 and 15 μM concentrations of vanillin oxime elevated Bax, caspase-3, and -9 levels in A549 and NCI-H2170 cells were observed. Vanillin oxime exposure suppressed levels of Bcl-2, survivin, Bcl-xL, cFLIP, and IAPs proteins in A549 and NCI-H2170 cells. It stimulated significant elevation in DR4 and DR5 levels in A549 and NCI-H2170 cells. In A549 and NCI-H2170 cells vanillin oxime exposure caused significant (p < 0.05) enhancement in CHOP and DR5 mRNA expression. Vanillin oxime exposure of A549 and NCI-H2170 cells led to significant (p < 0.05) enhancement in levels of phosphorylated extracellular-signal-regulated kinase and c-Jun N-terminal kinase. Thus, vanillin oxime inhibits pulmonary cell proliferation via induction of apoptosis through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated pathway. Therefore, vanillin oxime may be studied further to develop a treatment for lung cancer.

• Journal of Hospice and Palliative Care
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• v.26 no.1
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• pp.7-17
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• 2023

Purpose: The purpose of this study was to analyze end-of-life care practices in lung disease patients with physician orders for life-sustaining treatment (POLSTs). Methods: We retrospectively analyzed data from medical records regarding the end-of-life care practices of POLST decisions for patients with lung disease hospitalized at a tertiary hospital in Seoul, South Korea. Data were collected from January 1 to June 30, 2021. Results: Of 300 total patients, 198 had lung cancer (66.0%) and 102 had non-malignant lung diseases (34.0%). A POLST was written for 187 patients (62.3%), and an advance directive was written for 20 patients (6.7%). Subsequent treatments were hemodialysis in 13 patients (4.3%), surgery in 3 patients (1.0%), and cardiopulmonary cerebral resuscitation in 1 patient (0.3%). Among cancer patients, chemotherapy was performed in 11 patients (3.7%), targeted therapy in 11 patients (3.7%), immunotherapy in 6 patients (2.0%), and radiation therapy in 13 patients (4.3%). Depending on the type of lung disease, types of treatment differed, including hemodialysis, ventilators, bilevel positive airway pressure, high-flow nasal cannulas, nebulizers, enteral nutrition, central line, inotropic agents, and opioids. Conclusion: Although the goals of hospice care are the same whether a patient has lung cancer or a non-malignant lung disease, because the characteristics of the respective diseases differ, end-of-life care practices and hospice approaches must be considered differently.

• Journal of the Korean Magnetic Resonance Society
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• v.18 no.1
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• pp.10-14
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• 2014

Hsp90 is a good drug target molecule that is involved in regulating various signaling pathway in normal cell and the role of Hsp90 is highly emphasized especially in cancer cells. Thus, much efforts for discovery and development of Hsp90 inhibitor have been continued and a few Hsp90 inhibitors targeting the N-terminal ATP binding site are being tested in the clinical trials. There are no metabolic signature molecules that can be used to evaluate the effect of Hsp90 inhibition. We previously found a potential C-domain binder named PPC1 that is a synthetic small molecule. Here we report the metabolomics study to find signature metabolites upon treatment of PPC1 compound in lung cancer cell line, A549 and discuss the potentiality of metabolomic approach for evaluation of hit compounds.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.151-157
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• 1999

Background: Increasing evidences from experimental studies indicate that apoptosis may be inversely related to angiogenesis in tumor progression. Material and Method: To explore how apoptosis correlates with tumor angiogenesis, we measured the apoptotic index(AI) using the terminal deoxynucleotidyl transferase method(Apop Tag In Situ Apoptosis Detection Kit, ONCOR) and the intratumoral microvessel density using the anti-CD31 monoclonal antibody in non-small cell lung cancer. Result: Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities in squamous cell lung carcinoma(Spearman rank correlation coefficient r=- 0.229, p=0.047). Conclusion: The results of this study demonstrated that the amount of apoptosis in squamous cell lung carcinoma may be influenced by the extent of neovascularization. This suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.494-504
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• 2024

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.310-317
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• 1992

Background: Angiotensin converting enzyme is a glycoprotein peptidyldipeptide hydrolase which cleaves the c-terminal dipeptides of several oligopeptides. It is a menbrane-bound protein mainly synthesized by the endothelial cells. Since the lung has the largest capillary bed of any organ in the body, it is here that ACE acts on circulating substrates like angiotensin I and bradykinin. It is well known that ACE correlates with disease activity in sarcoidosis and also there are reports that changes in serum ACE activity are found in many acute and chronic lung diseases. So we planned this study to see if serum ACE activity can act as a prognostic factor in lung cancer. Methods: Forty-one newly diagnosed lung cancer patients were included in the study group. There were 19 patients with squamous cell lung cancer, 13 with adenocarcinoma, and 9 with small cell carcinoma. Patients were excluded from the study if they had high blood pressure, heart disease, liver disease, renal disease, or other lung disease. Serum ACE activity was analyzed according to cell type, staging, mode of treatment, and clinical response to treatment. Results: 1) There was no difference in serum ACE activity between lung cancer patients and the control group. Also no difference in serum ACE activity was found according to cancer cell type or staging. 2) In patients who underwent curative resection of lung cancer, serum ACE activity was decreased significantly after the operation. 3) In patients who were diagnosed as non-small cell lung cancer and were treated with 4 cycles of anti-cancer chemotherapy without clinical improvement, changes in serum ACE activity were not seen after the treatment. 4) In patients diagnosed as small cell lung cancer treated with 4 cycles of anti-cancer chemotherapy with clinical improvement, changes in serum ACE activity were also not observed. Conclusion: Serum ACE activity was decreased after lung resection but had no relation to cell type, staging, or clinical response to treatment in lung cancer patients. Therefore, serum ACE activity is not suitable in predicting clinical outcome of lung cancer patients.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.562-570
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• 2018

Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.214-219
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• 1998

Pain is one of the most frequent and disturbing symptom of cancer patients. And almost of cancer patients are afraid of a attacks of pain related to cancer. Caring for the cancer patient can be divided into two phases. The phase of "active treatment" involves various interventions-surgical, chemical or radiological- that are designed to prolong the patient's life. "Terminal care" is the period from the end of active treatment until the patient's death. But in the majority of clinical settings, cancer pain is not being managed adequately results from a lack of education about how to treat the cancer pain management in the safest and most effective way during terminal phase. Althought organic factors represent the most important cause of their pain, it is also important to deal with the patient's psychological reactions and to take account of his or her social and family environment if treatment for chronic cancer pain is to prove adequate. Thus we try to evaluate a kinds of cancer related to pain, degree of pain, effectiveness of drugs, and patient's responses to management. In regard to the satisfaction for pain relief in pain clinics at Pusan National University Hospital(PNUH) are about 70% in patients and 90% in family. Average life expectancy in cancer patients are about 140 days (3 days- 5.7 years). Cancer patients are complained of several discomfortness (above 30 kinds) such as, pain associated with cancer (75%), nausea and vomitting (38%), sleeping disorder (38%), anorexia (38%), dyspnea (32%), constipation (31%), etc. Distributions of cancer associated with pain are stomach cancer (21%), lung cancer (16%), cervix cancer (10%), anorectal and colon cancer (8.6%), hepatoma (8%), pancreatic cancer (3%). About 1/3 of patients are suffer from incident pain in 3~5 times in a day especially in moving, coughing, and exercise. Methods for drug delivering system before death are transdermal fentanyl patch (42%), intravenous PCA (21%), oral intake of opioid (17%), epidural PCA (14%), etc.

• Journal of Hospice and Palliative Care
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• v.23 no.1
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• pp.11-16
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• 2020

Purpose: D-dimer levels are known to be associated with poor outcomes in patients with various cancers, but their significance at the end of life remains unclear. This study investigated D-dimer levels as a prognostic indicator for terminal cancer patients in the last hours of life. Methods: The retrospective study was conducted at a palliative care unit of a tertiary cancer center, using a database to analyze the records of patients treated from January 1, 2010 to December 31, 2018. In total, 67 terminal cancer patients with available data on D-dimer levels were included. Patients' demographic data, clinical information, and laboratory values, including D-dimer levels, were collected. Survival was analyzed using the Kaplan-Meier method and the log-rank test. A Cox proportional-hazards model was used to identify prognostic factors of poor survival. Results: The most common site of cancer was the lung (32.8%) and the median survival time was 5 days. Most laboratory results, particularly D-dimer levels, deviated from the normal range. Patients with high D-dimer levels had a significantly shorter survival time than those with low D-dimer levels (4 days vs. 7 days; P=0.012). In the Cox regression analysis, only a high D-dimer level was identified as a predictor of a poor prognosis (hazard ratio, 1.83; 95% confidence interval, 1.09~3.07). Conclusion: Our results suggest that at the very end of life, D-dimer levels may serve as a prognostic factor for survival in cancer patients.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.211-217
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• 2005

Objectives : Terminal stage cancer patient from primary hepatocellular carcinoma metastasized into lungs was administered with cultivated wild ginseng herbal acupuncture for 5 months and observed progression. Methods : Cultivated wild ginseng herbal acupuncture was administered 5 times a week at about 150cc dosage per week. Dynamic CT was taken and interpreted at a university hospital. Results : Above patient was diagnosed with hepatocellular carcinoma and received one procedure of lobectomy and three procedures of TACE, but because of metastasis, chance of improvement was very obscure. Intensive treatment of cultivated wild ginseng herbal acupuncture five times a week for five months in association with moxibustion was done on the patient. Near elimination of the cancer cells metastasized into lungs were confirmed in terms of radiological impression through dynamic CT. Conclusion: From the results obtained in this study, cultivated wild ginseng herbal acupuncture can be an effective measure against terminal stage cancer. But this is a single case study and lack of extensive follow-up must be compensated by further researches.