• Journal of Acupuncture Research
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• v.31 no.1
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• pp.121-130
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• 2014

Objectives : I investigated whether bee venom inhibit cell growth through enhancement of death receptor expressions in the human lung cancer cells, NCI-H460. Methods : Bee venom(1-5 ${\mu}g/ml$) inhibited the growth of NCI-H460 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of TNF-R1, TNF-R2, FAS, death receptors(DR) 3, 4, 5 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including Caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-kB were inhibited by treatment with bee venom in NCI-H460 cells through TNF response change led by TNF-R1 and TNF-R2. Conclusions : These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in NCI-H460 human lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• Journal of Acupuncture Research
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• v.30 no.1
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• pp.57-70
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• 2013

This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

• Korean Journal of Hospice Care
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• v.3 no.2
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• pp.34-54
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• 2003

Every one experiences death one day, however no one can knows exactly what it is because people can not experience death until it comes, it is therefore impossible to judge correctly on the phenomenon of the death. On the whole, man experiences indirect death through the mass communications such as TV drama, fiction, magazine etc because those methods can easily access by every one. In addition to this, people usually acquire the negative awareness of death through the dramatic change of story like dying of cancer for dramatic effect by giving scare and fear to the cancers. The purpose of this study is to provide basic information on the spiritual care that enables the facing death patients to accept death as a part of life and divert hope from scare about after death by comparing and analyzing of two aspects of death meaning I.e, Korean fiction and the end stage cancer patients. Additionally, for medical staff to understand the facing death cancer patients by making to aware patients correctly and provide the better quality of care. The study was performed from September 28, 2002 to February, 28 2003. The materials of this study were collected by direct data obtained from observation, interviews, note and diary of end stage of cancer patients and written materials acquired from Korean contemporary fiction. Participants of this study were 4 end stage cancer patients including 2 lung cancer patients, 1 liver cancer patient and 1 esophagus cancer patient. The methodology used in this study was divided into two types; Huberman & Miles methodology was used for fiction to find and categorize subject, and Colaizzi, one of phenomenological methodology was used for end stage cancer patients to find the major meaning, subject and categorization. 1.The death investigated in the fiction, was found as a progress of negative emotion, acceptance and sublimation, life related subjects in the negative emotion were tenacity for life, anxiety, lingering attachment, responsibility, abandonment and death related subjects were shock, isolation, fear, scare and rejection. Acceptance related subjects were acceptance, destiny, secularism, preparation and arrangement, and sublimation related subjects were sublimation through Christian and Buddhism. 2.The death showed in the participants was negative emotion, acceptance and sublimation, life related subjects were repentance, anxiety, responsibility and hopelessness, and death related subjects were dejection, solitude, anger, fear and scare. The acceptance was a type of religious acceptance that admitted instantly by reaching an understanding with the God, and death was accepted as a progress of preparation, arrangement, acceptance and hope. Sublimation related subjects were Christian sublimation and relief or destiny incurred from self-reflective sublimation through communications and thoughts. 3.The death in view of fiction and participants were positively accepted both death and negative emotion, and the study disclosed the fact that death was sublimated dependent on religion. 4.The progress of negative emotion, acceptance and sublimation was disclosed more complicated and various in the real end stage cancer patients and acceptance only found in the patients on the form of religious acceptance, according to the results compared with fiction and real end stage cancer patients. The death showed in the fiction was standardized, gradated and similar progress with psychological status of Kubler-Ross. However, death in the participants was showed complex and various feelings simultaneously, and sometimes they accepted death positively. The sublimation through religion was found in Buddhism and Christian in the fiction and mostly Christian in the participants due to a number of Hospice patients. It was found that negative emotion various types of death was more found in the participants than fiction. It is therefore necessary to study on the response of death in various types. In the participants death was incurred more systematic and variously, we knew that nursing practice focused on experience of participants is required and reality on death is much profound than we analyzed and presented, lots of situations and reactions should be premised because we can not completely rule out the negligence possibility of care mediation of participants. In caring for the facing death patients, we discovered and confirmed again through this study that the spiritual care should be needed as a mediation method.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2405-2408
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• 2012

This descriptive study was performed to determine levels of the death anxiety levels of relatives of patients who being treated in a public hospital located in the Asian side of Istanbul and influencing factors. The sample was 106 patient relatives of patients from oncology or chemotherapy units of the hospital. Data were collected between May-June 2011 with the 15-item Death Anxiety Scale developed by Templer (1970) and adapted to Turkish by Senol (1989) and evaluated by number-percentage calculations, the Kruskal Wallis, Anova and t tests. Some 36.8% of the included group were aged 45 years and over, 57.5% were female and 65.1% were married. A statistically significant difference was found between the age groups, genders of the patient relatives, the period of cancer treatment regarding the death anxiety levels (p<0.05). The death anxiety levels of the patient relatives who were in the 17-39 age group, female and had a patient who was under treatment for less than 6 months were found to high as compared to others.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.526-535
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• 2023

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3617-3619
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• 2012

Background: The completeness of cancer registration is a major validity index of any reported cancer incidence. The present study aimed to evaluate the esophageal cancer incidence registered in the Tehran Metropolitan Area Cancer Registry. Materials and methods: The data on esophageal cancer abstracted from three sources of 1) pathology departments, 2) medical records, and 3) death certificates during 2003 till 2007 were utilized. The completeness of the data sources were evaluated using coverage (defined as the proportion of a community population with esophageal cancer identified by the source) and density (defined as the proportion of non-empty fields of the data by source). Results: A total 1,404 cases of esophageal cancer were reported for the duration of the study. Pathology provided 771, medical records 432, and death certificates 609. The coverage was 0.55 for pathology, 0.31 for medical records, and 0.43 for death certificates. The respective density values were 0.82, 0.96 and 0.98, respectively. Pathology (0.45) was the most complete source followed by medical records (0.42), and death certificates (0.29). Discussion: A low degree of completeness dictates putting more effort into case finding plus abstracting data more thoroughly.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.167-175
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• 2014

Chemotherapy has long been considered as one of useful strategies for cancer treatment. It is primarily based on the apoptosis that can selectively kill cancer cells. However, cancer cells can progressively develop an acquired resistance to apoptotic cell death, rendering refractory to chemo- and radiotherapies. Although the mechanism by which cells attained resistance to drug remains to be clarified, it might be caused by either pumping out of them or interfering with apoptotic signal cascades in response to cancer drugs. In case that cancer cells are defective in some part of apoptotic machinery by repeated exposure to anticancer drugs, alternative cell death mechanistically distinct from apoptosis could be adopted to remove cancer cells refractory to apoptosis-inducing agents. This review will mainly deal with harnessing of necrotic cell death, specifically, programmed necrosis and practical uses. Here, we begin with various defects of apoptotic death machinery in cancer cells, and then provide new perspective on programmed necrosis as an alternative anticancer approach.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5681-5685
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• 2012

Three kinds of survival rates are generally used depending on the purpose of the investigation: overall, cause-specific, and relative. The differences among these 3 survival rates are derived from their respective formulas; however, reports based on actual cancer registry data are few because of incomplete information and short follow-up duration recorded on cancer registration. The aim of this study was to numerically and visually compare these 3 survival rates on the basis of data from the Nagasaki Prefecture Cancer Registry. Subjects were patients diagnosed with cancer and registered in the registry between 1999 and 2003. We calculated the proportion of cause of death and 5-year survival rates. For lung, liver, or advanced stage cancers, the proportions of cancer-related death were high and the differences in survival rates were small. For prostate or early stage cancers, the proportions of death from other causes were high and the differences in survival rates were large. We concluded that the differences among the 3 survival rates increased when the proportion of death from other causes increased.

• Molecules and Cells
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• v.38 no.2
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• pp.138-144
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• 2015

Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the estrogen receptor (ER), and exhibits potent anti-tumor and autophagy-inducing effects in breast cancer cells. However, the mechanism of raloxifene-induced cell death and autophagy is not well-established. So, we analyzed mechanism underlying death and autophagy induced by raloxifene in MCF-7 breast cancer cells. Treatment with raloxifene significantly induced death in MCF-7 cells. Raloxifene accumulated GFP-LC3 puncta and increased the level of autophagic marker proteins, such as LC3-II, BECN1, and ATG12-ATG5 conjugates, indicating activated autophagy. Raloxifene also increased autophagic flux indicators, the cleavage of GFP from GFP-LC3 and only red fluorescence-positive puncta in mRFP-GFP-LC3-expressing cells. An autophagy inhibitor, 3-methyladenine (3-MA), suppressed the level of LC3-II and blocked the formation of GFP-LC3 puncta. Moreover, siRNA targeting BECN1 markedly reversed cell death and the level of LC3-II increased by raloxifene. Besides, raloxifene-induced cell death was not related to cleavage of caspases-7, -9, and PARP. These results indicate that raloxifene activates autophagy-dependent cell death but not apoptosis. Interestingly, raloxifene decreased the level of intracellular adenosine triphosphate (ATP) and activated the AMPK/ULK1 pathway. However it was not suppressed the AKT/mTOR pathway. Addition of ATP decreased the phosphorylation of AMPK as well as the accumulation of LC3-II, finally attenuating raloxifene-induced cell death. Our current study demonstrates that raloxifene induces autophagy via the activation of AMPK by sensing decreases in ATP, and that the overactivation of autophagy promotes cell death and thereby mediates the anti-cancer effects of raloxifene in breast cancer cells.

• Molecules and Cells
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• v.44 no.5
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• pp.363-373
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• 2021

Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.