• Title/Summary/Keyword: Self Targeting Therapy

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Emerging Role of NRF2 Signaling in Cancer Stem Cell Phenotype

  • Steffanus P. Hallis;Jin Myung Kim;Mi-Kyoung Kwak
    • Molecules and Cells
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    • v.46 no.3
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    • pp.153-164
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    • 2023
  • Cancer stem cells (CSCs) are a small population of tumor cells characterized by self-renewal and differentiation capacity. CSCs are currently postulated as the driving force that induces intra-tumor heterogeneity leading to tumor initiation, metastasis, and eventually tumor relapse. Notably, CSCs are inherently resistant to environmental stress, chemotherapy, and radiotherapy due to high levels of antioxidant systems and drug efflux transporters. In this context, a therapeutic strategy targeting the CSC-specific pathway holds a promising cure for cancer. NRF2 (nuclear factor erythroid 2-like 2; NFE2L2) is a master transcription factor that regulates an array of genes involved in the detoxification of reactive oxygen species/electrophiles. Accumulating evidence suggests that persistent NRF2 activation, observed in multiple types of cancer, supports tumor growth, aggressive malignancy, and therapy resistance. Herein, we describe the core properties of CSCs, focusing on treatment resistance, and review the evidence that demonstrates the roles of NRF2 signaling in conferring unique properties of CSCs and the associated signaling pathways.

The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

  • Oh, Jisun;Yoon, Hyo-Jin;Jang, Jeong-Hoon;Kim, Do-Hee;Surh, Young-Joon
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.421-430
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    • 2019
  • Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

The Effect of Self-Efficiency and Instrumental Activities of Daily Living of Local Community Stroke Patients on Quality of Life in Caregiver (지역사회 거주 뇌졸중환자의 수단적 일상생활동작과 자기 효능감이 보호자의 삶의 질에 미치는 영향)

  • Ko, June;Lee, Seung-Hee;Lee, Tae-Kwan;Jung, Hye-Rim;Hong, Geun-Ho;Hong, Ki-Hoon
    • The Journal of Korean society of community based occupational therapy
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    • v.5 no.1
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    • pp.11-21
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    • 2015
  • Objective : This study is aimed to examine the degree of independence in stroke patients residing in a community based on their self-efficacy and Instrumental Activities of Daily Living and also correlation between community-residing stroke patients and their guardians by figuring out the life quality of their guardians. Methods : For total two weeks between May 12th and 23rd, 2014, this researcher collected data by using a survey (K-IADL, a scale to measure self-efficacy, WHOQOL-BREF) targeting 138 stroke patients who received over 24 points in MMSE-K among the outpatients of three hospitals located in Busan Metropolitan City and two hospitals located in Geoje-si, Gyeongsangnam-do, and total 125 sheets were finally used for analysis. Results : Among the 125 patients, 70 were males, and 55 were females, and their average age was 58.72 (16 to 82). The subjects' general self-efficacy (p<0.01) and detailed self-efficacy (p<0.01) indicated significant correlation with their guardian's life quality, and there was no significant correlation found between their Instrumental Activities of Daily Living and their guardian's life quality. Conclusion : Their general self-efficacy and detailed self-efficacy indicated correlation with their guardian's life quality, and among their general characteristics, the factor of their financial situation indicated correlation with their guardian's life quality. In conclusion, when stroke patients' self-efficacy is higher, their guardian's life quality increases, too, and if their financial situation is more favorable, their guardian's life quality gets higher. However, stroke patients' Instrumental Activities of Daily Living did not indicate correlation with their guardian's life quality. When looking at the chronic trend of outpatients, therapeutical plan must be established about the self-efficient recovery for the development of those who are not satisfied.

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Immunotherapy with methyl gallate, an inhibitor of Treg cell migration, enhances the anti-cancer effect of cisplatin therapy

  • Kim, Hyunseong;Lee, Gihyun;Sohn, Sung-Hwa;Lee, Chanju;Kwak, Jung Won;Bae, Hyunsu
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.261-268
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    • 2016
  • $Foxp3^+$ $CD25^+CD4^+$ regulatory T (Treg) cells are crucial for the maintenance of immunological self-tolerance and are abundant in tumors. Most of these cells are chemo-attracted to tumor tissues and suppress anti-tumor responses inside the tumor. Currently, several cancer immunotherapies targeting Treg cells are being clinically tested. Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. While cisplatin is a powerful drug for the treatment of multiple cancers, there are obstacles that limit its use, such as renal dysfunction and the development of cisplatin-resistant cancer cells after its use. To minimize these barriers, combinatorial therapies of cisplatin with other drugs have been developed and have proven to be more effective to treat cancer. In the present study, we evaluated the effect of the combination therapy using methyl gallate with cisplatin in EL4 murine lymphoma bearing C57BL/6 mice. The combinatorial therapy of methyl gallate and cisplatin showed stronger anti-cancer effects than methyl gallate or cisplatin as single treatments. In Treg cell-depleted mice, however, the effect of methyl gallate vanished. It was found that methyl gallate treatment inhibited Treg cell migration into the tumor regardless of cisplatin treatment. Additionally, in both the normal and cisplatin-treated tumor-bearing mice, there was no renal toxicity attributed to methyl gallate treatment. These findings suggest that methyl gallate treatment could be useful as an adjuvant method accompanied with cisplatin therapy.

Physicochemical Characterization and Carcinoma Cell Interaction of Self-Organized Nanogels Prepared from Polysaccharide/Biotin Conjugates for Development of Anticancer Drug Carrier

  • Park Keun-Hong;Kang Dong-Min;Na Kun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.9
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    • pp.1369-1376
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    • 2006
  • Self-organized nanogels were prepared from pullulan/biotin conjugates (PU/Bio) for the development of an effective anticancer drug delivery system. The degree of biotin substitution was 11, 19, and 24 biotin groups per 100 anhydroglucose units of pullulan. The physicochemical properties of the nanogels (PU/Bio1, 2 and 3) in aqueous media were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of all the samples was less than 300 nm with a unimodal size distribution. The critical aggregation concentrations (CACs) of the nanoparticles in distilled water were $2.8{\times}10^{-2},\;1.6{\times}10^{-2}$, and $0.7{\times}10^{-2}mg/ml$ for the PU/Bio1, 2, and 3, respectively. The aggregation behavior of the nanogels indicated that biotin can perform as a hydrophobic moiety. To observe the specific interaction with a hepatic carcinoma cell line (HepG2), the conjugates were labeled with rhodamine B isothiocyanate (RITC) and their intensities measured using a fluorescence microplate reader. The HepG2 cells treated with the fluorescence-labeled PU/Bio nanoparticles were strongly luminated compared with the control (pullulan). Confocal laser microscopy also confirmed internalization of the PU/Bio nanogels into the cancer cells. Such results demonstrated that the biotin in the conjugate acted as both a hydrophobic moiety for self-assembly and a tumor-targeting moiety for specific interaction with tumor cells. Consequently, PU/Bio nanogels would appear to be a useful drug carrier for the treatment of liver cancer.

The Effect of Major-related Voluntary Services on Community Spirit and Occupational Values of University Students (대학생의 전공관련 봉사활동이 공동체 의식과 직업가치관에 미치는 효과)

  • Kang, Su-Gyeong;Kim, Da-Hye;Kim, Sun-Hyuk;Noh, Si-Hong;Sin, Min-Gyou;Shin, Hue-In;Yun, Huo-Jenog;Lim, Dong-Wook;Oh, Myung-Hwa
    • Journal of Korea Entertainment Industry Association
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    • v.13 no.1
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    • pp.175-184
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    • 2019
  • This study aims to find out that major-related voluntary services of university students have an effect on forming their community spirit and occupational value somehow. This study carried out the survey targeting students in 'D' University, which is located at Jeonnam Province of Korea, on September 6 through 13, 2017. The self-administered questionnaire was structured in questions about community spirit and occupational value. 566 copies of the questionnaires handed out were collected. As a result, participation in voluntary services makes a significant difference according to gender, grade, and departments but major related voluntary services was ignificant difference according to departments. There was a significant difference in community spirit and occupational value of participants in voluntary services. However, major-related voluntary services showed significant difference in occupational value only. Based on the results of this study, it is necessary to develop a lot of volunteer programs in order to encourage students to join major-related voluntary activities.

Cancer stem cell theory and update in oral squamous cell carcinoma (구강 편평세포암종에서의 암줄기세포 이론과 최신 지견)

  • Kim, Deok-Hun;Yun, Jun-Yong;Lee, Ju-Hyun;Kim, Soung-Min;Myoung, Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.2
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    • pp.97-108
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    • 2011
  • Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

The Effects of Career Identity and Social Support on the Career Decision-Making Self-Efficacy of Career Interrupted Women with Experienced on Beauty Education (미용교육을 받고 있는 경력단절여성의 진로정체성과 사회적지지가 진로결정자기효능감에 미치는 영향)

  • Shin, Su-Jeong;Lee, In-Hee
    • Journal of Fashion Business
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    • v.22 no.4
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    • pp.145-159
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    • 2018
  • The present study was carried out to investigate the effects of career identity and social support on the career decision-making self-efficacy of women who have experienced career interruption. Furthermore, the aim was to seek effective measures for making a career decision for the successful re-employment of women with a break in their career. From March $3^{rd}$ to April $2^{nd}$, 2018, a survey was conducted targeting 380 career-interrupted, married women with age between 30-50 years and with work experience of more than six months. The selected subjects had received 1-9 months of beauty education from various vocational training institutes, beauty academies, and women's center in Seoul and Gyeonggi region. A total of 361 questionnaires were used for final analysis. The SPSS Program for data analysis, Cronbach's ${\alpha}$, exploratory factor analysis, factor analysis, frequency analysis, correlation analysis, and multiple regression analysis were employed for the study. The results of this study are as follows. It was apparent that the establishment of a career identity and social support could play important roles in creating a relation with new career decisions for re-employment. Thus, this study aims to provide basic data necessary for the successful career preparation in women with career interruption.

Quality of Life and Its Related Factors of Radiation Therapy Cancer Patients (방사선 치료를 받은 암환자의 삶의 질과 관련요인)

  • Shin, Ryung-Mi;Jung, Won-Seok;Oh, Byeong-Cheon;Jo, Jun-Young;Kim, Gi-Chul;Choi, Tae-Gyu;Lee, Sok-Goo
    • The Journal of Korean Society for Radiation Therapy
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    • v.23 no.1
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    • pp.21-29
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    • 2011
  • Purpose: The purpose of this master's thesis is to utilize basic data in order to improve the quality of life of cancer patients who received radiation therapy after analysing related factors that influence patient's quality of life and obtaining information about physical, mental problems of patients. Materials and Methods: By using a structured questionnaire about various characteristics and forms of support, I carried out a survey targeting 107 patients that experienced radiation therapy at a university hospital in the Daejeon metropolitan area from July 15 to August 15, 2010 and analysed the factors influencing quality of life. Results: In case of pain due to disease, 65.15 and painless 81.87 showed a high grade quality of life. As body weight decreases, the quality of life become lower. When the grade of quality of life according to economic characteristics was compared, all items except treatment period showed a difference (P=0.000). When the score of social support, family support, medical support and self-esteem was low, the mark of quality of life showed respectively 61.71, 68.77, 71.31, and 69.39 on the basis of 128 points. When the score of support form was high, the mark of quality of life showed 90.47, 83.29, 90.40, and 90.36 (P<0.05). When analyzing the correlation between social support, family support, medical support and self-esteem and the degree of quality of life, social support was 0.768, family support 0.596, medical support 0.434, self-esteem 0.516. They indicated the correlation of meaningful quantity statistically (P<0.01). The factors that improved the quality of life were married state, having a job and painless status. As monthly income increases, the quality of life was also much improved (P<0.05). Among the factors related to quality of life, social support and medical support and higher self-esteem scores of the quality of life score increased 0.979 point, 0.508 points and 1.667 point, respectively. Conclusion: In conclusion, the quality of life of cancer patients that received radiation treatment is related to social support, medical support and self esteem. Self-esteem is an important factor that influenced quality of life, so if government offers works that doesn't affect patient's health, they are a useful method that maximize self-esteem and lessen their financial burden at the same time. Along with these policies, the developments of the attention of medical and the program for cancer patient's family are needed for the purpose of improving quality of life of cancer patients. Lastly, medical team, patients and family have to cooperate in harmony to overcome difficulties of cancer patients.

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Experiences of Stroke Patients With Combined Treatment of Self-selected Oriental and Western Medicine (뇌졸중 환자의 자가 선택에 의한 한·양방 병행 치료 경험)

  • Han, Jin-Sook;Kim, Yang-Sin;Moon, Young-Sook;Han, Su-Jeong;Park, In-Sook;Lee, Sang-Hun;Kim, Ae-Ran
    • Journal of Digital Convergence
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    • v.12 no.6
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    • pp.375-384
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    • 2014
  • This research was done to determine and analyze a qualitative on the essential structure of the experiences of stroke patients with combined treatment of oriental and western medicine. Methods: Participants in this study were targeting 25 stroke patients who live mostly in D city and received the combined treatment of oriental and western medicine, but received oriental medicine treatments based on their own wills. Data were collected and recorded through in-depth interviews. Data analysis was conducted by Colaizzi's phenomenological method. Results: As a result, their acculturation were classified into 21 clusters of theme and 6 categories. Selected 6 categories as follows. 'being severely shocked from sudden attack', 'being depressed with rehabilitation', 'western therapy was more effective in emergency situations', 'having limitations in western therapy', 'selecting oriental therapy for themselves', 'discovering the meaning of rehabilitation in oriental therapy'. Conclusion: Based on these necessary data for systematic oriental rehabilitation development.