• Title/Summary/Keyword: terminal cancer

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In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.911-920
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    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

신앙이 말기 암환자 삶의 질에 미치는 영향

  • Gang Seung-Gye;kim Su-Ho;kim Sin-Su;Park Hui-Myeong;Song Geun-Ok;Won Ju-Hui;Lee Myeong-Suk;Lee Seong-Ok;Lee Eun-Ui;Lee Chae-Yeong;Lee Hyeon-Mi
    • Korean Journal of Hospice Care
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    • v.2 no.2
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    • pp.49-57
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    • 2002
  • Background: The purpose of this study is to find out to how much influence religion had on the quality of life in patients admitted to the hospice facility at Saemmul's House. Terminal cancer patients were assessed one to two weeks after admittance to Saemmul's House. Metohd: The subjects of this study were numbered at 75 patients and were admitted to the hospice facility at Sammul's house between January 2002 and July 2002. The data regarding quality of life was collected using a questionnaire prepared by the sammul Hospice and were analyzed by means of ANOVA and T-test. Result: As a result of this study, there was no noticeable difference in quality of physical, psychosocial life between the patients with conviction of salvation and the other patients. However, it shows that the former enjoyed a higher spiritual quality of life than the latter. In case of baptized patients and unbaptized patients, there were no differences in terms of physical and psychosocial quality of life, but the baptized patients demonstrated a higher spiritual quality of life. After admittance, patients were grouped by duration of conviction of salvation I.e., those that believed more than 5 years and those that believed less than 5 years. In terms of physical, psychosocial quality of life, there was little difference between the two groups. However, those who believed more than 5 years demonstrated a higher spiritual quality of life. However, there was no difference in quality of life among patients, regardless of their belief in God, after receiving spiritual care at the hospice. Conclusion: We got a few conclusions in accordance with result gained by this study. First, spiritual support is very important to improving quality of patients' lives in hospices. Second, hospice programs are needed keenly and spiritual support for patients from trained experts is needed 24 hours a day. Third, because trained experts(ministry) are urgently needed to lend spiritual support, hospice courses must be taught at all colleges of theology. Fourth, a hospice program must provide a proper atmosphere that can give spiritual support and therefore all hospices must build such as environment. Fifth, a tool for spiritual support of hospice must be developed.

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Modulation of G-CSF Secretion by Mutations of Non Alpha-Helical Region in N-Terminus (G-CSF 단백질 N-말단의 비 알파-Helix 영역의 돌연변이에 의한 분비 조절)

  • Park, Jeong-Hae;Park, Jung-Ae;Kang, Seok-Woo;Goo, Tae-Won;Chung, Kyung-Tae
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1778-1783
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    • 2011
  • Hematopoietic cytokines regulate production of blood cells by stimulating proliferation and differentiation of bone marrow cells. Among these hematopoietic cytokines, called hematopoitic growth factors, glranulocyte-colony stimulating Factor (G-CSF), which regulates growth of neutrophils, is one of important therapeutic factors because cancer patients suffer with neutropenia which is severe reduction of neutrophils after chemotherapy. Two groups of recombinant G-CSF have approved and used for therapeutic purposes and many researches are still on-going to produce recombinant G-CSF by different techniques. We engineered human G-CSF with Bombyx specific endoplasmic reticulum (ER) signal sequence, therefore, secretion of human G-CSF protein was improved in Bombyx mori-origined cell line, Bm5. The Bombyx ER signal sequence and human G-CSF matured protein region chimera was further remodeled at the N-terminus of matured G-CSF protein to understand roles of N-terminus on outer cellular secretion and/or production. Three different mutants were generated deleting three amino acids in non alpha-helical region in N-terminus in order to scan important amino acids for G-CSF secretion. One of 3 different N-terminal deletion mutants showed dramatically reduction of secreted amount of G-CSF indicating its important role on secretion. The data suggest that remodeling in non alpha-helical region of N-terminus is also important for recombinant G-CSF production.

Multi User-Authentication System using One Time-Pseudo Random Number and Personal DNA STR Information in RFID Smart Card (RFID 스마트카드내 DNA STR Information과 일회용 의사난수를 사용한 다중 사용자 인증시스템)

  • Sung, Soon-Hwa;Kong, Eun-Bae
    • The KIPS Transactions:PartC
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    • v.10C no.6
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    • pp.747-754
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    • 2003
  • Thia paper suggests a milti user-authentication system comprises that DNA biometric informatiom, owner's RFID(Radio Frequency Identification) smartcard of hardware token, and PKI digital signqture of software. This system improved items proposed in [1] as follows : this mechanism provides one RFID smartcard instead of two user-authentication smartcard(the biometric registered seal card and the DNA personal ID card), and solbers user information exposure as RFID of low proce when the card is lost. In addition, this can be perfect multi user-autentication system to enable identification even in cases such as identical twins, the DNA collected from the blood of patient who has undergone a medical procedure involving blood replacement and the DNA of the blood donor, mutation in the DNA base of cancer cells and other cells. Therefore, the proposed system is applied to terminal log-on with RFID smart card that stores accurate digital DNA biometric information instead of present biometric user-authentication system with the card is lost, which doesn't expose any personal DNA information. The security of PKI digital signature private key can be improved because secure pseudo random number generator can generate infinite one-time pseudo randon number corresponding to a user ID to keep private key of PKI digital signature securely whenever authenticated users access a system. Un addition, this user-authentication system can be used in credit card, resident card, passport, etc. acceletating the use of biometric RFID smart' card. The security of proposed system is shown by statistical anaysis.

Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition

  • Soung, Nak-Kyun;Kim, Hye-Min;Asami, Yukihiro;Kim, Dong Hyun;Cho, Yangrae;Naik, Ravi;Jang, Yerin;Jang, Kusic;Han, Ho Jin;Ganipisetti, Srinivas Rao;Cha-Molstad, Hyunjoo;Hwang, Joonsung;Lee, Kyung Ho;Ko, Sung-Kyun;Jang, Jae-Hyuk;Ryoo, In-Ja;Kwon, Yong Tae;Lee, Kyung Sang;Osada, Hiroyuki;Lee, Kyeong;Kim, Bo Yeon;Ahn, Jong Seog
    • Experimental and Molecular Medicine
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    • v.51 no.2
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    • pp.1.1-1.14
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    • 2019
  • Hypoxia-inducible factor-$1{\alpha}$ ($HIF-1{\alpha}$) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of $HIF-1{\alpha}$ in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of $HIF-1{\alpha}$ translation by binding to the C-terminal glycinerich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3'-untranslated region of $HIF-1{\alpha}$ mRNA. Moreover, MO-460 suppresses $HIF-1{\alpha}$ protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxiainduced tumor survival and thus offer an avenue for the development of novel anticancer therapies.

Ginsenoside fractions regulate the action of monocytes and their differentiation into dendritic cells

  • Lee, Yeo Jin;Son, Young Min;Gu, Min Jeong;Song, Ki-Duk;Park, Sung-Moo;Song, Hyo Jin;Kang, Jae Sung;Woo, Jong Soo;Jung, Jee Hyung;Yang, Deok-Chun;Han, Seung Hyun;Yun, Cheol-Heui
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.29-37
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    • 2015
  • Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

Neuroprotective Effects of Korean Kiwifruit against t-BHP-induced Cell Damage in PC12 Cells (국내산 참다래 추출물의 신경독성 방어효과)

  • Kim, Jeong-Hee;Yang, Hee-Kyoung;Hong, Hyun-Ju;Kang, Won-Young;Kim, Dong-Geon;Kim, Seong-Cheol;Song, Kwan-Jeong;King, Dale;Han, Chang-Hoon;Lee, Young-Jae
    • Korean Journal of Plant Resources
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    • v.23 no.2
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    • pp.165-171
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    • 2010
  • Oxidative stress induced by reactive oxygen intermediates has been implicated in a variety of human diseases including neurodegenerative disorders, cancer, cardiovascular and respiratory diseases, and mode of action of environmental toxicants. Tert-butylhydroperoxide (t-BHP) is an organic lipid hydroperoxide analogue, which is commonly used as a pro-oxidant for evaluating mechanisms involving oxidative stress in cells and tissues. In this study, the underlying mechanisms involved in the protective effects of Hwabuk 94 kiwifruit (Actinidia deliciosa cv. 'Hwabuk 94'), which is cultivated in Jeju, on the t-BHP-induced cytotoxicity in PC12 cell. The pretreatment of rat pheochromocytoma cell line PC12 with Hwabuk 94 extract ($1-100\;{\mu}g/ml$) resulted in a significant recovery from t-BHP-induced cell death and increased Bcl-2 and procaspase-3 expression, whereas the expression of Bax and cleaved PARP were decreased in a dose-dependent manner compared to the control. Furthermore, Hwabuk 94 inhibited the t-BHP-induced p38 MAP kinase and extracellular signal-regulated kinase 1/2, but not c-Jun N-terminal kinase activations. Finally, these findings suggest that Hwabuk 94 kiwifruit might attenuate t-BHP-induced PC12 cell cytotoxicity, at least in part, through the inhibition of signaling pathways mediated by the ERK1/2 and p38 MAP kinase.

A convergent meta-analysis of the effect of hospice nursing intervention (호스피스 간호중재 프로그램 효과에 관한 융·복합 메타분석)

  • Kim, Woon Soon
    • Journal of Digital Convergence
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    • v.16 no.11
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    • pp.419-432
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    • 2018
  • The purpose of this study is to develop a hospice intervention program and present basic study data using a method of Meta analysis. Fifteen theses from 2002 to 2017 were collected from the on-line database at Korean Education and Research Information Service and other journals related hospice. Main keywords were 'hospice' and intervention'. The selected 15 theses were analyzed with publication bias, outcome of effect size, non-overlap percentage(U3), 95% confidence intervals and homogeneity. The result of the study is summarized as follows; Publication bias was stable and the effect size of hospice program was significant at. 99. The effective and significant regulation effects were publication years with 2003 to 2007(ES=1.24), publication types with journals(ES=1.33), majors with nursing sciences(ES=1.02), ages with 29 to 30(ES=1.09), later session(ES=1.06) and aroma(ES=1.12). Accordingly, this thesis has its meaning in that it used a Meta-analysis to analyze domestic theses of hospice intervention programs for the first time in Korea. This thesis will prodide specific guidance to researchers trying to develop and utilize hospice intervention programs resulting in helpful usages in professional hospice institutions with implementations of programs.

Awareness of Doctors' Shared Decision-Making in Life-Sustaining Care Decisions

  • Kim, Dalyong;Lee, Hyun Jung;Yu, Soo-Young;Kwon, Jung Hye;Ahn, Hee Kyung;Kim, Jee Hyun;Seo, Seyoung;Maeng, Chi Hoon;Lim, Seungtaek;Kim, Do Yeun;Shin, Sung Joon
    • Journal of Hospice and Palliative Care
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    • v.24 no.4
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    • pp.204-213
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    • 2021
  • Purpose: At the end of life, communication is a key factor for good care. However, in clinical practice, it is difficult to adequately discuss end-of-life care. In order to understand and analyze how decision-making related to life-sustaining treatment (LST) is performed, the shared decision-making (SDM) behaviors of physicians were investigated. Methods: A questionnaire was designed after reviewing the literature on attitudes toward SDM or decision-making related to LST. A final item was added after consulting experts. The survey was completed by internal medicine residents and hematologists/medical oncologists who treat terminal cancer patients. Results: In total, 202 respondents completed the questionnaire, and 88.6% said that the decision to continue or end LST is usually a result of SDM since they believed that sufficient explanation is provided to patients and caregivers, patients and caregivers make their own decisions according to their values, and there is sufficient time for patients and caregivers to make a decision. Expected satisfaction with the decision-making process was the highest for caregivers (57.4%), followed by physicians (49.5%) and patients (41.1%). In total, 38.1% of respondents said that SDM was adequately practiced when making decisions related to LST. The most common reason for inadequate SDM was time pressure (89.6%). Conclusion: Although most physicians answered that they practiced SDM when making decisions regarding LST, satisfactory SDM is rarely practiced in the clinical field. A model for the proper implementation of SDM is needed, and additional studies must be conducted to develop an SDM model in collaboration with other academic organizations.

Assessment for the Needs to Develop Hospice Training Program for Nurses (간호사를 위한 호스피스 연수교육 요구도 조사)

  • Kwon, So-Hi;Yang, Seong-Kyeong;Park, Myung-Hee;Choe, Sang-Ok
    • Journal of Hospice and Palliative Care
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    • v.11 no.3
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    • pp.147-155
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    • 2008
  • Purpose: This study aimed to assess the educational needs for nurses who care for terminal cancer patients and their families. To identify top needs along with key issues in consideration to develope hospice training program and provide specific recommendations. Methods: A cross-sectional design with nurses from nine universities' hospice specialist courses and seven cancer centers was used. Data were collected via e-mail or mail service from March to April in 2008. One hundred seventy three questionnaires were returned (return rate: 73.6%), and 156 questionnaires were eventually analyzed. The questionnaire consisted of Mason and Ellershaw's The Self-efficacy in Palliative Care (SEPC) and self-reporting confidence and educational needs in hospice care. Results: The mean age of the participants was 37.94 years, 82.1% were staff nurses, and 44.9% completed over six months hospice education. Mean$\pm$standard deviation score for total SEPC was $2.67{\pm}.62$, which was lower than average (score 3), with communication score being the lowest ($2.49{\pm}.69$). The lowest self-reporting confidence score was $2.03{\pm}.77$ in hospice administration and management, followed by providing complement therapy ($2.34{\pm}.77$), bereavement care ($2.34{\pm}.71$), lymph edema management ($2.35{\pm}.79$), and care planning ($2.36{\pm}.81$). The participants reported that additional education is needed in all topics, with pain management score being the highest ($3.71{\pm}.50$), followed by pain and symptom evaluation ($3.67{\pm}.52$), care for dying ($3.67{\pm}.52$), and communication and counseling ($3.63{\pm}.53$). There were significant subgroup differences in SEPC and self-reporting confidence between groups who completed 6 months hospice education or not, however, no significant difference in educational need between the groups. Conclusion: This study showed the need for developing hospice training program to improve compentency of nurses in hospice palliative care.

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