• Title/Summary/Keyword: differentiation therapy

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CDDO-Me alleviates oxidative stress in human mesenchymal stem cells

  • Cho, Hye Jin;Kim, Tae Min
    • Journal of Animal Reproduction and Biotechnology
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    • v.36 no.4
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    • pp.285-291
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    • 2021
  • Mesenchymal stem cells (MSCs) have been recognized as a therapeutic tool for various diseases due to its unique ability for tissue regeneration and immune regulation. However, poor survival during in vitro expansion and after being administrated in vivo limits its clinical uses. Accordingly, protocols for enhancing cell survivability is critical for establishing an efficient cell therapy is needed. CDDO-Me is a synthetic C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, which is known to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Herein, report that CDDO-Me promoted the proliferation of MSCs and increased colony forming units (CFU) numbers. No alteration in differentiation into tri-lineage mesodermal cells was found after CDDO-Me treatment. We observed that CDDO-Me treatment reduced the cell death induced by oxidative stress, demonstrated by the augment in the expression of Nrf2-downstream genes. Lastly, CDDO-Me led to the nuclear translocation of NRF2. Our data indicate that CDDO-Me can enhance the functionality of MSCs by stimulating cell survival and increasing viability under oxidative stress.

Ginseng-derived compounds as potential anticancer agents targeting cancer stem cells

  • Ji-Sun Lee;Ho-Young Lee
    • Journal of Ginseng Research
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    • v.48 no.3
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    • pp.266-275
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    • 2024
  • Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

  • Alexandra A. Wolfarth;Swati Dhar;Jack B. Goon;Ugonna I. Ezeanya;Sara Ferrando-Martínez;Byung Ha Lee
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.5.1-5.22
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    • 2022
  • The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

Effects of Vitexin from Mung Bean on 3T3-L1 Adipocyte Differentiation and Regulation According to Adipocytokine Secretion (녹두의 Vitexin이 비만전구세포에서 세포분화 및 아디포사이토카인 분비능에 미치는 영향)

  • Wi, Hae-Ri;Choi, Mun-Ji;Choi, Se-Lim;Kim, Ae-Jung;Lee, Myoung-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.8
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    • pp.1079-1085
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    • 2012
  • Obesity is an important issue worldwide as it may associated with increased prevalence of metabolic diseases. Mung bean is known as a functional food for decreasing the glycemic index and lipid profile of plasma. The purpose of this study was to investigate the anti-obesity effects of vitexin from mung bean on the regulation of adipocyte differentiation and adipocytokine secretion. When 3T3-L1 adipocytes were treated with vitexin from days 0 to 14 at various levels of 25, 50, 100, and $200{\mu}M$, there was no change in cell viability. Vitexin treatment at 50, 100, and $200{\mu}M$ decreased triacylglycerol levels in cells, but only $100{\mu}M$ vitexin induced lipolysis. At $200{\mu}M$ of vitexin, phosphorylation of p38 and ERK, which causes secretion of inflammatory adipocytokines, was depressed, whereas there was an increase in expression of $PPAR{\gamma}$, the key regulator of adipocyte differentiation. Phosphorylation of AMPK increased at $100{\mu}M$ vitexin. TNF-${\alpha}$ and aP2 mRNA expression increased at $25{\mu}M$ vitexin, whereas only TNF-${\alpha}$ mRNA expression increased at $200{\mu}M$ vitexin. Further, the mRNA levels of TNF-${\alpha}$ and aP2 decreased at other concentrations in a dose-dependent manner. Since we observed that mRNA expression of C/EBP, SREBP1, and $PPAR{\gamma}$ did not change upon vitexin treatment, our future studies will investigate other genes such as mTOR, which is related with apoptosis signaling, or SIRT1, which is associated with inhibition of adipogenesis. Our results indicate that vitexin at concentrations between 100 and $200{\mu}M$ is suitable in vivo for the development of mung bean as an anti-obesity therapy or functional food.

Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia over three Decades

  • Roder, David;Karapetis, Christos S;Wattchow, David;Moore, James;Singhal, Nimit;Joshi, Rohit;Keefe, Dorothy;Fusco, Kellie;Powell, Kate;Eckert, Marion;Price, Timothy J
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2431-2440
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    • 2015
  • Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

Metastatic Colorectal Cancer Treatment and Survival: the Experience of Major Public Hospitals in South Australia Over Three Decades

  • Roder, David;Karapetis, Christos S;Wattchow, David;Moore, James;Singhal, Nimit;Joshi, Rohit;Keefe, Dorothy;Fusco, Kellie;Buranyi-Trevarton, Dianne;Sharplin, Greg;Price, Timothy J
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5923-5931
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    • 2015
  • Background: Registry data from four major public hospitals indicate trends over three decades from 1980 to 2010 in treatment and survival from colorectal cancer with distant metastases at diagnosis (TNM stage IV). Materials and Methods: Kaplan-Meier product-limit estimates and Cox proportional hazards models for investigating disease-specific survival and multiple logistic regression analyses for indicating first-round treatment trends. Results: Two-year survivals increased from 10% for 1980-84 to 35% for 2005-10 diagnoses. Corresponding increases in five-year survivals were from 3% to 16%. Time-to-event risk of colorectal cancer death approximately halved (hazards ratio: 0.48 (0.40, 0.59) after adjusting for demographic factors, tumour differentiation, and primary sub-site. Survivals were not found to differ by place of residence, suggesting reasonable equity in service provision. About 74% of cases were treated surgically and this proportion increased over time. Proportions having systemic therapy and/or radiotherapy increased from 12% in 1980-84 to 61% for 2005-10. Radiotherapy was more common for rectal than colonic cases (39% vs 7% in 2005-10). Of the cases diagnosed in 2005-10 when less than 70 years of age, the percentage having radiotherapy and/or systemic therapy was 79% for colorectal, 74% for colon and 86% for rectum (&RS)) cancers. Corresponding proportions having: systemic therapies were 75%, 71% and 81% respectively; radiotherapy were 24%, 10% and 46% respectively; and surgery were 75%, 78% and 71% respectively. Based on survey data on uptake of offered therapies, it is likely that of these younger cases, 85% would have been offered systemic treatment and among rectum (&RS) cases, about 63% would have been offered radiotherapy. Conclusions: Pronounced increases in survivals from metastatic colorectal cancer have occurred, in keeping with improved systemic therapies and surgical interventions. Use of radiotherapy and/or systemic therapy has increased markedly and patterns of change accord with clinical guideline recommendations.

Beneficial Effect of Ginseng Extract on Sudden Sensorineural Hearing Loss (돌발성난청에서 홍삼추출물의 추가적인 치료효과)

  • Im, Gi-Jung;Cinn, Young-Gi;Chang, Ji-Won;Choi, Joan;Chae, Sung-Won;Jung, Hak-Hyun
    • Journal of Ginseng Research
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    • v.33 no.2
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    • pp.155-159
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    • 2009
  • Sudden idiopathic sensorineural hearing loss is a disease that develops within several hours to several days. Its etiology has not yet been verified, but the disturbance of the circulation of blood in the inner ear, inner-ear hydrops, and viral infection are considered possible causes of the disease. This study was conducted to evaluate the effect of Panax ginseng extract, which is known to have a vasodilatory effect, on sudden sensorineural hearing loss. Sixty-nine patients suffering from sudden sensorineural hearing loss were admitted to Korea University Anam Hospital from March to December 2008. They were divided into the experimental (30 ears) and control (39 ears) groups. Ginseng extract (2700 mg/day, 4 weeks) was added to the therapeutic regimen in the experimental group. The effect of ginseng extract therapy was analyzed according to the factors relating to the prognosis. A considerable hearing improvement was documented in both groups (32.2 dB in the experimental group and 25.8 dB in the control group). However, there was little beneficial effect of ginseng extract on additional hearing improvement compared with control. The total recovery rate of the experimental group (80.0%) was better than that of the control group (58.9%), and the experimental group's high-tone hearing gain at 3 kHz (29.7 dB) was better than that of the control group (21.7 dB). The results of the study suggest that the effects of ginseng therapy tend to be superior to those of the conventional therapy, but the difference between the two is not statistically significant. The hearing gains tend to be in the higher frequencies and may be due to the promotion of cellular differentiation from the supporting cells.

A Literature study on the external therapy of contact dermatitis. (接觸性皮膚炎의 外治法에 關한 文獻的 考察)

  • Jeon, Jae-hong;Kim, Hyun-a;Kang, Yun-ho;Ho
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.11 no.1
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    • pp.197-218
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    • 1998
  • In this study, I invastigate about oriental medical drug, dosage form and directions in external therapy of contact dermatitis. and after study on relationship oriental medical drug, dosage form and directions with cause, symptom and differentiation of symptom and sign. The results are as follows; 1. Most frequently used oriental medical drug is until qing(淸) dynasty Eriocheir sinensis H. Milne-Edwards(蟹), Salix babylonica L.(柳葉), Natrii sulfas(芒硝), Allium macrostemon Bge.(해), Nelumbo nucifera Gaertn.(荷葉), nowadays in Korea and China Phellodendron amurense Rupr.(黃柏), Gypsum(石膏), Rheum palmatum L.(大黃), Baphicacanthus cusia Bremek(靑黛), Talcum(滑石). 2. In the frequency of dosage form, until qing(淸) dynasty powder 1case, liquor 49cases, liquer and solid mixture 58cases, nowadays Korea and China powder 16cases, liquor 96cases, liquer and solid mixture 59cases. 3. Most frequently used directions of dosage is thinly attaching method(薄貼法), attaching method(敷貼法), furnigating and cleansing method(熏洗法), cleansing method(洗傷法), wet dressing method(濕敷法), spreading powder method(撲粉法), plaster method(途차法), rubbing skin method(摩擦法) 4. In the external therapy of contact dermatitis, oriental medical drug's usage is based on stage of contact dermatitis In acute stage, most frequently used drug is heat and damp remove drug(淸熱燥濕藥), nature of drug(藥性) is bitter taste and cold charactor(苦寒), In chronic stage, most frequently used drug is nourishing the blood drug(養血藥), promoting blood circulation drug(活血藥). 5. The dosage form of drug is based on symptom. In acute stage, when papules and vesicles, or erosion and exudation is the main symptom of skin, liquor or powder is used, when erosion and crust is the main symptom of skin, plaster is used. In chronic stage, plaster is used. 6. In the directions of dosage is based on dosage form of drug and symptom. In acute stage, when papules and vesicles is the main symptom of skin, fumigating and cleansing method, cleansing method, plaster method is used, when erosion, vesicles and exudation the main symptom of skill, cleansing method, wet dressing method, spreading powder method, attaching method, spreading powder method is used, when crust is the main symptom of skin, plaster method is used. In chronic stage, plaster method, rubbing skin method is used.

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Mesenchymal Stem Cell-derived Exosomes: Applications in Cell-free Therapy (중간엽줄기세포유래 엑소좀: 비세포치료제로서의 활용)

  • Heo, June Seok;Kim, Jinkwan
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.391-398
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    • 2018
  • Mesenchymal stem cells (MSCs) are an attractive resource for refractory patients because of their anti-inflammatory/immunomodulatory capability and multi-lineage differentiation potential. The transplantation of MSCs has led to positive results in preclinical and clinical application to various diseases, including autoimmune disease, cardiovascular disease, cancer, liver cirrhosis, and ischemic stroke. On the other hand, studies have shown that paracrine factors, not direct cell replacement for damaged cells or tissue, are the main contributors in MSC-based therapy. More recently, evidence has indicated that MSC-derived exosomes play crucial roles in regulating the paracrine factors that can mediate tissue regeneration via transferring nucleic acids, proteins, and lipids to the local microenvironment and cell-to-cell communication. The use of these exosomes is likely to be beneficial for the therapeutic application of MSCs because their use can avoid harmful effects, such as tumor formation involved in cell transplantation. Therefore, therapeutic applications using MSC-derived exosomes might be safe and efficient strategies for regenerative medicine and tissue engineering. This review summarizes the recent advances and provides a comprehensive understanding of the role of MSC-derived exosomes as a therapeutic agent.

Recent Research Trends in Thioredoxin Reductase-targeted Anticancer Therapy (Thioredoxin reductase를 표적으로 하는 항암 최신 연구 동향)

  • Hwangbo, Hyun;Lee, Hyesook;Cheong, JaeHun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.1
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    • pp.63-69
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    • 2022
  • The thioredoxin reductase (TrxR) system is essential for cell survival and function by playing a pivotal role in maintaining homeostasis of cellular redox and regulating signal transduction pathways. The TrxR system comprises thioredoxin (Trx), TrxR, and nicotinamide adenine dinucleotide phosphate. Trx reduced by the catalytic reaction of the TrxR enzyme reduces downstream proteins, resulting in protection against oxidative stress and regulation of cell differentiation, growth, and death. Cancer cells survive by improving their intracellular antioxidant capacity to eliminate excessively generated reactive oxygen species (ROS) due to infinite cell proliferation and a high metabolic rate. Therefore, cancer cells have high dependence and sensitivity to antioxidant systems, suggesting that focusing on TrxR, a representative antioxidant system, is a potential strategy for cancer therapy. Several studies have revealed that TrxR is expressed at high levels in various types of cancers, and research on anticancer activity targeting the TrxR system is increasing. In this review, we discuss the feasibility and value of the TrxR system as a strategy for anticancer activity research by examining the relationship between the function of the intracellular TrxR system and the development and progression of cancer, considering the anticancer activity and mechanism of TrxR inhibitors.