• Title/Summary/Keyword: Cancer Stem Cell

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Development of a mouse model for pulp-dentin complex regeneration research: a preliminary study

  • Kim, Sunil;Lee, Sukjoon;Jung, Han-Sung;Kim, Sun-Young;Kim, Euiseong
    • Restorative Dentistry and Endodontics
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    • v.44 no.2
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    • pp.20.1-20.8
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    • 2019
  • Objectives: To achieve pulp-dentin complex regeneration with tissue engineering, treatment efficacies and safeties should be evaluated using in vivo orthotopic transplantation in a sufficient number of animals. Mice have been a species of choice in which to study stem cell biology in mammals. However, most pulp-dentin complex regeneration studies have used large animals because the mouse tooth is too small. The purpose of this study was to demonstrate the utility of the mouse tooth as a transplantation model for pulp-dentin complex regeneration research. Materials and Methods: Experiments were performed using 7-week-old male Institute of Cancer Research (ICR) mice; a total of 35 mice had their pulp exposed, and 5 mice each were sacrificed at 1, 2, 4, 7, 9, 12 and 14 days after pulp exposure. After decalcification in 5% ethylenediaminetetraacetic acid, the samples were embedded and cut with a microtome and then stained with hematoxylin and eosin. Slides were observed under a high-magnification light microscope. Results: Until 1 week postoperatively, the tissue below the pulp chamber orifice appeared normal. The remaining coronal portion of the pulp tissue was inflammatory and necrotic. After 1 week postoperatively, inflammation and necrosis were apparent in the root canals inferior to the orifices. The specimens obtained after experimental day 14 showed necrosis of all tissue in the root canals. Conclusions: This study could provide opportunities for researchers performing in vivo orthotopic transplantation experiments with mice.

Mechanism underlying Chios gum mastic-induced apoptosis on SCC25 human tongue squamous cell carcinoma cell line

  • Lee, Seung-Eun;Hur, Young-Joo;Kim, In-Ryoung;Kwak, Hyun-Ho;Kim, Gyoo-Cheon;Shin, Sang-Hun;Kim, Chul-Hoon;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.34 no.2
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    • pp.61-72
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    • 2009
  • Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is known also to induce cell cycle arrest and apoptosis in some cancer cells. In this study, we further investigated the induction and mechanisms underlying the apoptotic response to CGM treatment in the SCC25 human tongue squamous cell carcinoma cell line. The viability of SCC25 cells, human normal keratinocytes (HaCaT cells) and human gingival fibroblasts (HGF-1 cells), and the growth inhibition of SCC25 cells were assessed by MTT assay and clonogenic assay, respectively. Staining with Hoechst and hemacolor dyes and TUNEL assays were employed to detect SCC25 cells undergoing apoptosis. SCC25 cells were treated with CGM, and this was followed by western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, MMP activity and proteasome activity analyses. CGM treatment of SCC25 cells was found to result in a time- and dosedependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Interestingly, CGM showed a remarkable level of cytotoxicity in SCC25 cells but not in normal cells. Tested SCC25 cells also showed several lines of apoptotic manifestation. Taken together, our present findings demonstrate that CGM strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and induces apoptosis via the proteasome, mitochondria and caspase cascades in SCC25 cells.

Bark Constituents from Mushroom-detoxified $Rhus$ $verniciflua$ Suppress Kainic Acid-induced Neuronal Cell Death in Mouse Hippocampus

  • Byun, Jong-Seon;Han, Yoon-Hee;Hong, Sung-Jun;Hwang, Sung-Mi;Kwon, Yong-Soo;Lee, Hee-Jae;Kim, Sung-Soo;Kim, Myong-Jo;Chun, Wan-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.5
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    • pp.279-283
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    • 2010
  • Urushinol, a plant allergen, has significantly restricted the medical application of $Rhus$ $verniciflua$, although it has been reported to possess a wide variety of biological activities such as anti-inflammatory, antioxidant, and anti-cancer actions. To reduce the urushinol content while maintaining the beneficial biological activities, mushroom-mediated fermentation of $Rhus$ $verniciflua$ was carried out and this method resulted in significantly attenuated allergenicity [1]. In the present study, to examine the neuroprotective properties of mushroom-fermented stem bark of $Rhus$ $verniciflua$, two constituents were isolated from mushroom-fermented bark and their neuroprotective properties were examined in a mouse model of kainic acid (KA)-induced excitotoxicity. KA resulted in significant apoptotic neuronal cell death in the CA3 region of mouse hippocampus. However, seven daily administrations of RVH-1 or RVH-2 prior to KA injection significantly attenuated KA-induced pyramidal neuronal cell death in the CA3 region. Furthermore, pretreatment with RVH-1 and RVH-2 also suppressed KA-induced microglial activation in the mouse hippocampus. The present study demonstrates that RVH-1 and RVH-2 isolated from $Rhus$ $verniciflua$ and detoxified using mushroom species possess neuroprotective properties against KA-induced excitotoxicity. This leads to the possibility that detoxified $Rhus$ $verniciflua$ can be a valuable asset in herbal medicine.

Study of Rat Mammary Epithelial Stem Cells In Vivo and In Vitro (생체 및 시험관에서 유선 상피 모세포의 분리와 동정)

  • Nam Deuk Kim;Kee-Joo Paik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.3
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    • pp.470-486
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    • 1995
  • Mammary epithelial cells contain a subpopulation of cells with a large proliferativ potential which are responsible for the maintenance of glandular cellularity and are the progenitor cells of mammary cancer. These clonogens give rise to multicellular clonal alveolar or ductal units(AU or DU) on transplantation and hormonal stimulation. To isolate putative mammary clonogens, enzymatically monodispersed rat mammary epithelial cells from organoid cultures and from intact glands are sorted by flow cytometry according to their affinity for FITC labeled peanut lectin(PNA) and PE labeled anti-Thy-1.1 antibody(Thy-1.1) into four subpopulations : cells negative to both PNA and Thy-1.1(B-), PNA+cells, Thy-1.1+cells, and cells positive to both reagents(B+). The in vivo transplantation assays indicate that the clonogenic fractions of PNA+cells from out-growths of organoids in primary cultures for three days in complete hormone medium(CHM) are significantly higher than those of cells from other subpopulations derived from cultrues or from intact glands. Extracellular matrix(ECM) is a complex of several proteins that regulated cell function ; its role in cell growth and differentiation and tissue-specific gene expression. It can act as a positive as well as a negative regulator of cellular differentiation depending on the cell type and the genes studied. Regulation by ECM is closely interrelated with the action of other regulators of cellular function, such as growth factors and hormones. Matrigel supports the growth and development of several different multicellular colonies from mammary organoids and from monodispersed epithelial cells in culture. Several types of colonies are observed including stellate colonies, duct-like structures, two- and three-dimensional web structures, squamous organoids, and lobulo-duct colonies. Organoids have the greatest proliferative potential and formation of multi-cellular structures. Phase contrast micrographs demonstrate extensive intracellular lipid accumulation within the web structures and some of duct-like colonies. At the immunocytochemical and electron micrograph level, casein proteins are predominantly localized near the apical surface of the cells or in the lumen of duct-like or lobulo-duct colonies. Squamous colonies are comprised of several layers of squamous epithelium surrounding keratin pearls as is typical fo squamous metaplasia(SM). All-trans retinoic acid(RA) inhibits the growth of SM. The frequency of lobulo-ductal colony formation increased with the augmentation of RA concentration in these culture conditions. The current study models could provide powerful tools not only for understanding cell growth and differentiation of epithelial cells, but also for the isolation and characterization of mammary clonogenic stem cells.

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Immature thymocyte antigen, JL1, as a possible immunodiagnostic and immunotherapeutic target for leukemia

  • Shin, Young Kee;Choi, Eun Young;Kim, Seok Hyung;Park, Seong Hoe
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.1-6
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    • 2001
  • The identification of tumor-specific antigens has represented a critical milestone in cancer diagnosis and therapy. Clinical research in this area for leukemia has also been driven over the past few decades by the hope that surface antigens with restricted tissue expression would be identified. Disappointingly, only a small number of the leukemic antigens identified to date, meet sufficient criteria to be considered viable immunophenotypic markers. In this paper, we nominate anti-JL1 monoclonal antibody as an immunodiagnostic and immunotherapeutic candidate for leukemia. The JL1 molecule appears to be a novel cell surface antigen, which is strictly confined to a subpopulation of limited stages during the hematopoietic differentiation process. Despite the restricted distribution of the JL1 antigen in normal tissues and cells, anti-JL1 monoclonal antibody specifically recognizes various types of leukemia, irrespective of immunophenotypes. On the basis of these findings, we propose JL1 antigen as a tumor-specific marker, which shows promise as a candidate molecule for diagnosis and immunotherapy in leukemia, and one that spares normal bone marrow stem cells.

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Cytotoxic Constituents from the Stem Bark of Chisocheton pentandrus

  • Retnowati, Rurini;Sulistyarti, Hermin;Wahidah, Nikmatus Zahro;Syarifah, Anisa Lailatusy;Salam, Suprianto;Nurlelasari, Nurlelasari;Safari, Agus;Harneti, Desi;Tanjung, Mulyadi;Hidayat, Ace Tatang;Maharani, Rani;Supratman, Unang;Shiono, Yoshihito
    • Natural Product Sciences
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    • v.27 no.1
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    • pp.18-27
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    • 2021
  • Eight cytotoxic constituents, consisting of six triterpenoids, cabralealactone (1), cabraleadiol (2), prototiamin A (3), 23-desmethyllimocin B (5), melianodiol (7) and indicalilacol (8) along with one limonoid, neemfruitins A (4) and one protolimonoid, protoxylocarpin G (6), were isolated from the extract of n-hexane of the stembark of Chisocheton pentandrus. The chemical structures were identified on the basis of spectroscopic evidence and compared to previously reported spectra. These isolated compounds appear for the first time in the plant. Compounds 1 - 8 were evaluated for their cytotoxic effect against MCF-7 breast cancer lines in vitro. Among the isolated compounds, melianodiol (7) showed the strongest cytotoxic activity with IC50 values of 16.8 µM.

A review on Phytochemistry and pharmacological Activities of Cirsium setidens (Dunn) Nakai (고려엉겅퀴(Cirsium setidens (Dunn) Nakai)의 구성성분 및생리활성에 관한 리뷰)

  • MiAe Cho;Bumjung Kim
    • The Korea Journal of Herbology
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    • v.38 no.4
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    • pp.31-43
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    • 2023
  • Objectives : The objective of this study was to investigate the phytochemistry and pharmacological activities of Cirsium setidens. Methods : Domestic and international articles about Cirsium setidens were investigated. A review was perfoemed via DB searching engine such as Sci.Direct, Springer, DBpia, KISS, Google scholar, Kipris, and so on. Total 73 listed literature were classified by compound analysis and pharmacological efficacy. Results : C. setidens contains pectolinarin and its glycoside, pectolinarigenin as index compounds, and linarin, apigenin, diosmetin, scopoletin, acacetin, cirsimarin, cirsimaritin, setidenosides A and B, silymarin, hispidulin, 92 volatile compounds, and 15 fatty acids. The Pharmacological activities of C. setidens has been reported to inhibit of platelet aggregation and fat accumulation in the liver, inhibit to hepatitis, anti-cancer, antibacterial, skin improvement, hair growth, liver protection, anti-diabetic, anti-inflammatory, sedative. Also, It has been reported the effect of cholesterol-lowering and anti-obesity, neuroprotective effects, increasing human stem cell viability, inhibiting osteoclast formation and osteogenic differentiation. Conclusion : This reviews showed that C. setidens which has been traditionally used for the treatment of inflammation and hypertension, has anticancer and river protective effect, as well as hair loss and diet. In order to maximize the efficacy of C. setidens, research has also begun on the effect of processing processes such as fermentation or fine powdering and combining natural plant resources.

Weight status in survivors of childhood acute lymphocytic leukemia in South Korea: a retrospective descriptive study

  • Yeongseon Kim;Kyung-Sook Bang
    • Child Health Nursing Research
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    • v.29 no.4
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    • pp.280-289
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    • 2023
  • Purpose: This study investigated weight status in survivors of childhood acute lymphocytic leukemia (ALL) and identified related factors. Methods: A retrospective review of the electronic medical records of survivors of childhood ALL (n=230) was conducted. We analyzed the survivors' characteristics, including sex, age, weight status at diagnosis, central nervous system involvement, risk classification, length of treatment, radiation therapy, and hematopoietic stem cell transplantation. Analysis of variance and the chi-squared test were applied to investigate influencing factors. Results: The weight status distribution was as follows: 23 individuals (10.0%) were classified as underweight, 151 individuals (65.7%) were healthy weight, and 56 individuals (24.3%) were overweight/obese. Age at diagnosis (F=10.03, p<.001), weight status at diagnosis (x2=43.41, p<.001), and risk classification (F=10.98, p=0.027) showed significant differences among the weight status groups. Survivors who were older at diagnosis and those in the very high-risk category had a higher likelihood of experiencing underweight status during their survivorship, while survivors who were overweight/obese at diagnosis were more likely to remain overweight/obese at the time of survival. Conclusion: Considering the potential health implications related to an unhealthy weight status in survivors of ALL, it is imperative to undertake early identification and implement interventions for at-risk individuals.

Secretion and Expression of Matrix Metalloproteinase-2 and 9 from Bone Marrow Mononuclear Cells in Myelodysplastic Syndrome and Acute Myeloid Leukemia

  • Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Shanmukaiah, Chandrakala;Nadkarni, Anita H
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1519-1529
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    • 2016
  • Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.

Deletion of GSTM1 and T1 Genes as a Risk Factor for Development of Acute Leukemia

  • Dunna, Nageswara Rao;Vure, Sugunakar;Sailaja, K.;Surekha, D.;Raghunadharao, D.;Rajappa, Senthil;Vishnupriya, S.
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2221-2224
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    • 2013
  • The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M & GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.