• Title/Summary/Keyword: Terminal Cancer

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SUV39H1 is a New Client Protein of Hsp90 Degradated by Chaetocin as a Novel C-Terminal Inhibitor of Hsp90

  • Lian, Bin;Lin, Qian;Tang, Wei;Qi, Xin;Li, Jing
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.73-82
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    • 2021
  • Hsp90 is often overexpressed with activated form in cancer cells, and many key cellular proteins are dependent upon the Hsp90 machinery (these proteins are called "client protein"). Nowadays, more client proteins and more inhibitors of Hsp90 are being discovered. Chaetocin has been identified as an inhibitor of histone methyl transferase SUV39H1. Herein, we find that Chaetocin is an inhibitor of Hsp90 which binds to the C-terminal of Hsp90α. Chaetocin inhibited a variety of Hsp90 client proteins including AMl1-ETO and BCL-ABL, the mutant fusion-protein in the K562 and HL-60 cells. SUV39H1 mediates epigenetic events in the pathophysiology of hematopoietic disorders. We found that inhibition of Hsp90 by Chaetocin and 17-AAG had ability to induce degradation of SUV39H1 through proteasome pathway. In addition, SUV39H1 interacted with Hsp90 through co-chaperone HOP. These results suggest that SUV39H1 belongs to a client protein of Hsp90. Moreover, Chaetocin was able to induce cell differentiation in the two cells in the concentration range of Hsp90 inhibition. Altogether, our results demonstrate that SUV39H1 is a new client protein of Hsp90 degradated by Chaetocin as a novel C-terminal inhibitor of Hsp90. The study establishes a new relationship of Chaetocin and SUV39H1, and paves an avenue for exploring a new strategy to target SUV39H1 by inhibition of Hsp90 in leukemia.

The Comparison between High Dose and Low Dose Morphine in Terminal Cancer Patients During the Last 1 Week to Death (고용량과 저용량의 몰핀을 쓰는 말기 암 환자에서 임종 1주일동안 비교)

  • Cho, Doo-Yeoun;Cha, Kyu-Jin;Yoon, Bang-Boo;Yeom, Chang-Hwan
    • Journal of Hospice and Palliative Care
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    • v.5 no.1
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    • pp.24-30
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    • 2002
  • Background : Pain is one of the most feared consequences of cancer. $65{\sim}85%$ of cancer patients experienced severe pain, and sometimes high dose morphine is used to these patients. But many doctors still have 'opioid-phobia' and hesitate to use high dose morphine. We investigated the morphine therapy in terminal cancer patients during the last 1 week to death, and found any differences according to the morphine dosage. Methods : 93 patients admitted to National Health Insurance Corporation Ilsan Hospital, department of family medicine for hospice care between September 2000 and the end of October 2001 and lived more than 1 week entered in the study. We investigated the demographic data, laboratory tests and sufficient dosage of morphine for pain control. According to the calculated dosage by OME(oral morphine equivalent), patients were divided into low dosage group (${\leq}150mg/day$) and high dosage group (>150 mg/day). The chi-squared test were used to evaluate the influence of age, gender, tumor sites, metastasis and adverse effects of morphine. Results : Mean age was $65.0{\pm}13.1year$ in low dosage group and $59.9{\pm}11.6year$ in high dosage group. 32 men (50.0%) and 32 women (50.0%) were included in low dosage group and 15 men (51.7%) and 14 women (48.3%) in high dosage group. Stomach was the most frequent tumor site and lung was the next. Metastasis were found 58 (90.6%) in low dosage group and 28 (96.6%) in high dosage group. In other palliative radiotherapy and adverse effects, there were no differences in both group. Conclusion : During the last 1 week to death in cancer patients, there were no difference according to the morphine dosage. So we don't have to have 'opioid-phobia' in treating the terminal cancer patients.

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Survey on Quality of Hospice.Palliative Care Programs in Korea (한국 호스피스.완화의료기관 실태 조사)

  • Yun, Young-Ho;Choi, Eun-Sook;Lee, In-Jeong;Rhee, Young-Sun;Lee, Jung-Suk;You, Chang-Hoon;Kim, Hyun-Sook;Paek, Yu-Jin
    • Journal of Hospice and Palliative Care
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    • v.5 no.1
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    • pp.31-42
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    • 2002
  • Purpose : The purpose of this study was to evaluate the present status of hospice palliative care programs in Korea as a basic database for standardization of hospice palliative care. Method : The data was collected from July to October, 2001. The instrument used for this study was the questionnaires which was consisted of the general characteristics of organization, recipient of service, manpower, contents of service, financial conditions and facilities. Sixty-four hospice palliative care programs answered the questionnaires, confirmed by telephone. Results : They were 40 hospital-based hospice palliative care programs and 24 nonmedical hospice palliative care programs. 11 Hospital-based hospice palliative programs have isolated unit or hospital affiliated free standing hospice. 6 Non-hospital hospice palliative programs have a free standing hospice. Major subjects of hospice palliative program were terminal cancer patients but patients with non-terminal illness were also included. Only 24 of 64 hospice palliative programs had all of the essential professionals : physicians, nurses, social workers, and clergies. Home hospice palliative care programs have a referral system in hospital based (89.7%) and nonmedical programs (73.7%). 24hr hospice are were provided in 26 hospital-based (65.0%) and 9nonmedical programs (37.5%). There were rooms for family in half of hospital-based programs. 73.9% of hospice palliative care programs have financial problems. 62.0% of Hospice palliative care programs need financial support from government. Conclusion : 64 Hospice palliative care programs provided hospice palliative services but had many problems in manpower, quality of care and facility. For improving the quality of terminal patients' life and promoting the cost effectiveness of health care resources, it is necessary to consider the standardization and institutionalization of hospice palliative care.

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Calcium-induced Human Keratinocytes(HaCaT) Differentiation Requires Protein Kinase B Activation in Phosphatidylinositol 3-Kinase-dependent Manner

  • Piao, Longzhen;Shin, Sang-Hee;Yang, Keum-Jin;Park, Ji-Soo;Shin, Eul-Soon;Li, Yu-Wen;Park, Kyung-Ah;Byun, Hee-Sun;Won, Min-Ho;Lee, Choong-Jae;Hur, Gang-Min;Seok, Jeong-Ho;Kim, Ju-Duck
    • Toxicological Research
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    • v.22 no.3
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    • pp.283-291
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    • 2006
  • The survival and growth of epithelial cells depends on adhesion to the extracellular matrix. An adhesion signal may regulate the initiation of differentiation, since epidermal keratinocytes differentiate as they leave the basement membrane. A metabolically dead cornified cell envelope is the end point of epidermal differentiation so that this process may be viewed as a specialized form of programmed cell death. In order to investigate the precise cellular signaling events loading to terminal differentiation of keratinocytes, we have utilized HaCaT cells to monitor the biological consequences of $Ca^{2+}$ stimulation and numerous downstream signaling pathways, including activation of the extracellular signal-regulated protein kinase(ERK) pathway and activation of phosphatidylinositol 3-kinase(PI3K). The results presented in this study show that $Ca^{2+}$ function as potent agents for the differentiation of HaCaT keratinocytes, and this differentiation depends or the activation of ERK, Protein kinase B(PKB) and p70 ribosomal protein S6 kinase(p70S6K). Finally, the results show that the expression of Activator protein 1(AP-1; c-Jun and c-Fos) increased following $Ca^{2+}$-mediated differentiation of HaCaT cells, suggesting that ERK-mediated AP-1 expression is critical for initiating the terminal differentiation of keratinocytes.

말기암환자 가족에 대한 호스피스 케어의 정보적 지지 제공 효과

  • Kim, Hyeon-Suk
    • Korean Journal of Hospice Care
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    • v.2 no.1
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    • pp.21-40
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    • 2002
  • Cancer is the second leading cause of the death in Korea. Family caregivers of dying patients manifest many psychological and physical symptoms of stress, and they often seek for informational support from health care providers. Unfortunately, however, few systematic studies identify the actual effect of such support on family caregivers. This study, thus, intends to evaluate the effect of informational support for hospice care. One group pretest-posttest design was used, employing the stress-coping model by Cohen and Wills as a conceptual framework. This research was conducted from July 1 to November 15, 1998, initially with 32 subjects sampled from hemato-oncology department of two general hospitals in Seoul, but reduced to 18 at the end due to the untimely death of patients or caregiver's refusal during the course of study. Informational supports were programmed to provide the family caregivers with 8 times of education and counseling as well as 24-hour hot-line for 4 weeks. A booklet that explains the various problems of hospice care was also prepared and distributed to all subjects. Data were collected by using self-report questionnaires and reviewing medical records. The tools used in this study were based on the Weinert's PRQ-II(scale of perceived social support), Spielberger's state anxiety inventory, and CES-D. Also included in the data collection were the general characteristics of family caregivers and patients, and the pain intensity and the performance status of patients. The data were analyzed with descriptive statistics, Wilcoxon sign rank test and paired t-test using SPSSWIN program. The results of the study were as follows: 1.The perceived social support of family caregivers was not significantly increased with informational support for hospice care(t=1.64, one tailed p=.060). 2.The anxiety of family caregivers was significantly reduced following informational support for hospice care(t=3.48, one tailed p=.002). 3.The depression of family caregivers was significantly reduced following informational support for hospice care(t=-2.18, one tailed=.022). 4.The pain intensity of patients with terminal cancer was significantly reduced following informational support for hospice care(t=-2.41, two tailed p=.027). The results suggest that the informational support provided to family caregivers of patients with terminal cancer reduced not only their anxiety and depression but also the pain intensity of patients. Further study is necessary to consolidate the conceptual framework of this study with expanded number of subjects. Nevertheless, it was certain that the informational support program for hospice care was very helpful to both caregivers and patients. Thus, the informational support program is strongly recommended for the hospitals which have no hospice unit yet.

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The Effects of Hospice Care in Public Health Centers on Quality of Life of Terminal Cancer Patients and Care-giver Burden of Families (말기 암 환자의 삶의 질과 주 돌봄자 부담감에 관한 보건소 호스피스 사업의 효과)

  • Kim, In-Hong;Han, Young-Ran
    • Journal of agricultural medicine and community health
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    • v.33 no.1
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    • pp.59-70
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    • 2008
  • Objectives: This study aimed to find out the effects of hospice care in public health centers by evaluating the quality of life of terminal cancer patients and care-giver burden of their families.Methods: From January to December 2007, 32 terminal cancer patients and their familes were selected as with interviews. Instruments used for this study were C-QOL(Cancer-Quality of Life) that was developed by Le(207) and care-giver burden of families that was developed by Seo et al(193). The data were analyzed using frequency, percentage and paired t-test.

Serum Levels and Glycosylation Changes of Alpha-1-Acid Glycoprotein According to Severity of Breast Cancer in Korean Women

  • Choi, Jae Woong;Jeong, Ki-Ho;You, Ji Won;Lee, Jun Woo;Moon, Byung-In;Kim, Hyoung Jin;Kim, Hong-Jin
    • Journal of Microbiology and Biotechnology
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    • v.30 no.9
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    • pp.1297-1304
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    • 2020
  • Elevated serum levels of alpha-1-acid glycoprotein (AGP) are known to be associated with several types of cancer. In addition, some reports have indicated that changes in glycosylation of AGP are associated with cancer progression. However, changes in AGP levels of serum and changes in glycosylation of AGPs in breast cancer have not been specifically studied. In the present study, serum AGP levels in benign (BN) cancer and breast cancer stage I (BC I), BC IIA, BC IIB, and BC III in Korean women were measured using an enzyme-linked immunosorbent assay (ELISA). AGP was purified from individual sera by hot phenol extraction and then subjected to AGP glycosylation analysis. Three types of AGP glycosylation (fucosylation, high-mannose-type and sialylation) were detected using enzyme-linked lectin assays (ELLAs). Serum AGP levels were higher in BC I, BC IIA, BC IIB, and BC III, than in the BN group, and the level in BC I and BC IIA was high enough to be distinguished from BN. Meanwhile, terminal fucosylation and high-mannose-type glycans appeared to be lowest in BC I. The glycosylation levels of BC I provide sensitivity and specificity that make BC I clearly distinguishable from BC IIA, BC IIB, and BC III as well as BN. Therefore, determination of serum AGP or AGP glycosylation level could be useful for detecting the early stages of breast cancer.

The Effect of Aroma Therapy on Lower Extremity Edema of Terminal Cancer Patients: A Controlled Trial (아로마 요법이 말기 암 환자의 하지부종에 미치는 영향 - 대조군 연구)

  • Kim, Sung-Ah;Kim, Sung-Ju;Chung, Ju-Hye;Lee, Soo-Young;Han, Myung-Suk;Oh, Seon-Hee;Kim, Se-Hong
    • Journal of Hospice and Palliative Care
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    • v.12 no.3
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    • pp.139-146
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    • 2009
  • This study was designed to examine the effect of aroma massage therapy on lower extremity edema of terminal cancer patients. Methods: A total of thirty-six terminal cancer patients with lower extremity edema were divided into two groups: the aroma massage group received massage with blending oil which was applied from toes to 10 cm above the knee of the subject for 15 to 20 minutes in each turn, while the control group received sham aroma massage (applied with carrier oil only). The circumferences of the fore-foot, ankle and calf were measured before massage and 30 minutes, 2 hours, and 12 hours after massage. The blood pressure, pulse and body temperature were also measured to find the change of subject's physiologic conditions. Results: There were no significant differences in blood pressure, heart rate, body temperature and lower extremity circumferences between two groups. However, edema at each site was slightly improved in the treatment group after the aroma massage therapy, compared to baseline data (P<0.05). In addition, the reduction of lower extremity circumference was maximal at 2 hours in foot, 30 min in right ankle and 12 hours in right calf after aroma massage therapy (P<0.05). Conclusion: Our results suggest that aroma massage therapy is not effective on the lower extremity edema of terminal cancer patients.

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DNR (Do-Not-Resuscitate) Order for Terminal Cancer Patients at Hospice Ward (호스피스 병동에서 시행되는 말기 암 환자의 DNR (Do-Not-Resuscitate) 동의)

  • Shim, Byoung-Yong;Hong, Seok-In;Park, Jin-Min;Cho, Hong-Joo;Ok, Jong-Sun;Kim, Seon-Young;Han, Sun-Ae;Lee, Ok-Kyung;Kim, Hoon-Kyo
    • Journal of Hospice and Palliative Care
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    • v.7 no.2
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    • pp.232-237
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    • 2004
  • Purpose: DNR order is generally accepted for cancer patients near the end of life at Hospice Ward. It means not only no CPR when cardiopulmonary arrest develops but no aggressive meaningless medical interventions. Usually on admission, we discuss with the patients' family about DNR order at the Hospice Ward. Recently, we experienced a terminal lung cancer patient who had been on the ventilator for two months after pulmonary arrest. CPR and artificial ventilation were performed because patient's family refused DNR order. There is no consensus when, who, and how DNR order could be written for terminal cancer patients in Korea, yet. Methods: Hospice charts of 60 patients who admitted between Jan and Jun 2003 to Hospice Ward were reviewed retrospectively. Results: The median age was 66(range $31{\sim}93$) and there were 31 males and 29 females. Their underlying cancers were lung (12), stomach (12), biliary tract (7), colon (6), pancreas (4) and others (19). The persons who signed DNR order were son (22), spouse(19), daughter (16) and others (3). But, there was no patients who signed DNR order by oneself. Thirty families of 60 patients signed on day of admission and 30 signed during hospitalization when there were symptom aggravation (19), vital sign change (4), organ failure (3) and others (4). There were 13 patients who died within 5 days after DNR order. Most of patients died at our hospice ward, except in 1 patient. The level of care was mostly 1, except in 2 patients. (We set level of care as 3 categories. Level 1 is general medical care: 2 is general nursing care: 3 is terminal care.) Conclusion: We have to consider carefully discussing DNR order with terminal cancer patients in the future & values on withholding futile intervention.

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Symptom Prevalence During Terminal Cancer Patients' Last 48 Hours of Life (말기 암 환자에서 임종 전 48시간 동안 나타나는 신체적 증상 빈도)

  • Jung, Soo-Jin;Lee, Bok-Ki;Choi, Kyung-Hi;Youn, Bang-Bu;Yeom, Chang-Hwan
    • Journal of Hospice and Palliative Care
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    • v.5 no.1
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    • pp.17-23
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    • 2002
  • Purpose : The prevalence of symptoms in patients with terminal cancer varies considerably and these symptoms are very difficult to control. However, patients can spend their last days or hours of life without suffering pain with appropriate care. One of the major concerns during last days of life is to predict the time of death. We would like to investigate symptom prevalence during terminal cancer patients' last 48 hours in Korea, and therefore contribute to predict the time of death and to help to determine appropriate treatments. Methods : The data for this study was recorded from 92 of 132 patients who died with terminal cancer at the hospital between February 1 and October 31, 2000. We investigated the symptom prevalence during the last 48 hours through medical obligation record and analyzed the changes of symptom prevalence at the admission, $48{\sim}24$ hours and $24{\sim}0$ hours before death. Results : The predominant symptom prevalence was pain (57.6%), followed by confusion (55.4%), dyspnea (48.9%), voiding difficulty (42.4%) in the last 48 hours before death. From the statistical analysis for the changes of symptom prevalence in time, pain, nausea and vomiting were decreased but noisy and moist breathing, sweating, groan, restlessness and agitation, and loss of consciousness were increased (P<0.05). Conclusion : The results from this study show the tendency to increase of prevalence of noisy and moist breathing, sweating, groan, restlessness and agitation as well as loss of consciousness in 48 hours before death. Therefore the symptoms above can be used for the important indicators to predict the imminent death.

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