• Title/Summary/Keyword: Cell-of-origin

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Comparing the Benefits and Drawbacks of Stem Cell Therapy Based on the Cell Origin or Manipulation Process: Addressing Immunogenicity

  • Sung-Ho Chang;Chung Gyu Park
    • IMMUNE NETWORK
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    • v.23 no.6
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    • pp.44.1-44.16
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    • 2023
  • Mesenchymal stem cells (MSCs) are effective in treating autoimmune diseases and managing various conditions, such as engraftment of allogeneic islets. Additionally, autologous and HLA-matched allogeneic MSCs can aid in the engraftment of human allogeneic kidneys with or without low doses of tacrolimus, respectively. However, HLA alloantigens are problematic because cell therapy uses more HLA-mismatched allogeneic cells than autologous for convenience and standardization. In particular, HLA-mismatched MSCs showed increased Ag-specific T/B cells and reduced viability faster than HLA-matched MSCs. In CRISPR/Cas9-based cell therapy, Cas9 induce T cell activation in the recipient's immune system. Interestingly, despite their immunogenicity being limited to the cells with foreign Ags, the accumulation of HLA alloantigen-sensitized T/B cells may lead to allograft rejection, suggesting that alloantigens may have a greater scope of adverse effects than foreign Ags. To avoid alloantigen recognition, the β2-microglobulin knockout (B2MKO) system, eliminating class-I MHC, was able to avoid rejection by alloreactive CD8 T cells compared to controls. Moreover, universal donor cells in which both B2M and Class II MHC transactivator (CIITA) were knocked out was more effective in avoiding immune rejection than single KO. However, B2MKO and CIITA KO system remain to be controlled and validated for adverse effects such as the development of tumorigenicity due to deficient Ag recognition by CD8 T and CD4 T cells, respectively. Overall, better HLA-matching or depletion of HLA alloantigens prior to cell therapy can reduce repetitive transplantation through the long-term survival of allogeneic cell therapy, which may be especially important for patients seeking allogeneic transplantation.

Expression of $O^6$-methylguanine-DNA methyltransferase and Sensitivity to Anticancer Alkylating Agents in Human Cancer Cells (사람 암세포에서의 $O^6$-methylguanine-DNA methyltransferase의 발현과 알킬화 항암제에 대한 감수성)

  • 오혜영;정해관;한의식;정성철;허옥순;손수정;김영미;홍성렬;이향우
    • Biomolecules & Therapeutics
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    • v.3 no.2
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    • pp.122-131
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    • 1995
  • Five human cancer cell lines (HeLa S3, Hep 3B, KATO III, Hs 683, HeLa MR) and one human normal cell line (WI-38) were examined cell viability, northern blot analysis, western blot analysis, and in situ hybridization for the expression $O_{6}$ -methylguanine-DNAmethyltransferase (MGMT), which can repair $O_{6}$ -methylguanine produced in DNA by alkylating agents. In cell viability test, the lethal sensitivities of each strain against anti-tumor drug N,N-bis(2-chloroethyl)- N-nitrosourea (BCNU) were counted, and both BCNU treated and untreated cell extracts were examined for their MGMT inducibility by RNA dot blot analysis. Cell lines did not show MGMT induction by BCNU pretreatment. Tlle MGMT activity was assayed by measuring the $^3$H radioactivity transferred from the substrate DNA containing [methyl-$^3$H)-O$_{6}$ -methylguanine to acceptor molecules in the cell extracts. Extracts from the majority of tumor strains and normal cells contained substantial MGMT activity of varying degree, while the known Mer$^{[-10]}$ cell (lacked or severely depleted in MGMT activity) Hela MR, and Hs 683 (proved to be Mer$^{[-10]}$ ) were much more sensitive to BCNU than the rest of tumor strains, as measured by cell viability test. Overall results above, KATO III showed the highest expression level of MGMT among the strains examined. Furthermore, with all the tumor and normal strains tested, a good correlation was observed between MGMT expression and cellular resistance to BCNU. The varying levels of expression of MGMT in human cancer cells found in this study should provide a molecular basis for MGMT expression among tumor strains from different tissue origin, the information of antitumor agents selection for chemotherapy of cancers.

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HIGH DOSE EXPOSURES OF VINYL ACETATE INDUCE NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (인체상피세포를 이용한 Vinyl acetate의 발암성 및 작용기전)

  • Cho, Jun-Hyun;Kim, Chin-Soo
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.5
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    • pp.437-444
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    • 2007
  • Vinyl acetate has been widely used for the manufacture of polyvinyl alcohol emulsion, which is primary ingredient of adhesive, paints, textile, paperboard coatings, etc. Since these products are plentiful and frequently used around us, workers and consumers are at health risk. International Agency for Research on Cancer(IARC) classified vinyl acetate as group 2B(possibly carcinogenic to humans). Among the organs targeted, the oral cavity is the most vulnerable organ affected by the carcinogenic effects of vinyl acetate. Since the origin of most of oral cancer is derived from the epithelial cells, it is important to understand the carcinogenic potential of vinyl acetate in human epithelial cells. Thus, the present study has attempted to utilize the immortalized human epithelial cell model to assess the carcinogenic potency of this chemical and to understand the underlying mechanisms.

MYIASIS IN A SUBMANDIBULAR METASTATIC SQUAMOUS CELL CARCINOMA ; A CASE REPORT (악하부에 전이된 편평상피암종에 발생한 승저증의 치험례)

  • Park, So-Young;Kwon, Tae-Geon;Kim, Jong-Bae;Joo, Chong-Yoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.5
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    • pp.550-554
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    • 2000
  • We report a case of myiasis on the left submandibular area after radiation therapy for squamous cell carcinoma. A 77-year-old man visited our hospital, 7 weeks after complicating a course of radiation therapy, had a 7cm diameter necrotic ulcer on the left submandible. The margin of the lesion were undermined by numerous interlinking passages containing 20 maggots. The maggots were removed by simple extraction and were identified as Calliphoridae Lucilia. The probable origin of the myiasis in this case was attributed to poor environmental condition and general weakness of the patient. Oppotunistic cutaneous myiasis can be prevented by protecting open wounds from flies, wound should not be left without a covering capable of excluding flies, especially in the summer month.

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The Role of Jak/STAT Pathways in Osteoclast Differentiation

  • Lee, Young-Kyun;Kim, Hong-Hee
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.141-148
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    • 2011
  • Osteoclasts are bone-resorbing cells of monocyte/macrophage origin and are culprits of bone destruction associated with osteoporosis, rheumatoid arthritis, and cancer bone metastasis. Recent advances in osteoclast biology revealed central roles of various cytokines in regulating osteoclastogenesis both in vitro and in vivo. However, exact underlying mechanisms including signaling pathways downstream of receptor ligation are still under pursuit. In the present review, the role of Jak/STAT proteins and their regulators will be discussed in connection with osteoclastogenesis, since growing evidence indicates that a number of cytokines and growth factors utilizing Jak/STAT signaling pathways affect osteoclastogenesis. A better understanding on the role of Jak/STAT pathways in osteoclast differentiation will not only strengthen our knowledge on osteoclast biology but also provide invaluable insights into the development of anti-resorptive strategies for treating bone-lytic diseases.

Flavonoids: An Emerging Lead in the P-glycoprotein Inhibition

  • Gadhe, Changdev G.;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.5 no.2
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    • pp.72-78
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    • 2012
  • Multidrug resistance is a major obstacle in cancer chemotherapy. Cancer cells efflux chemotherapeutic drug out of cell by means of transporter and reduce the active concentration of it inside cell. Such transporters are member of the ATP binding cassettes (ABC) protein. It includes P-gp, multiple resistant protein (MRP), and breast cancer resistant protein (BCRP). These proteins are widely distributed in the human cells such as kidney, lung, endothelial cells of blood brain barrier etc. However, there are number of drugs developed for it, but most of them are getting transported by it. So, still there is necessity of a good modulator, which could effectively combat the transport of chemotherapeutic agents. Natural products origin modulators were found to be effective against transporter such as flavonoids, which belongs to third generation modulators. They have advantage over synthetic inhibitor in the sense that they have simple structure and abundant in nature. This review focuses on the P-gp structure its architecture, efflux mechanism, herbal inhibitors and their mechanism of action.

The complex role of extracellular vesicles in HIV infection

  • Jung-Hyun Lee
    • BMB Reports
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    • v.56 no.6
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    • pp.335-340
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    • 2023
  • During normal physiological and abnormal pathophysiological conditions, all cells release membrane vesicles, termed extracellular vesicles (EVs). Growing evidence has revealed that EVs act as important messengers in intercellular communication. EVs play emerging roles in cellular responses and the modulation of immune responses during virus infection. EVs contribute to triggering antiviral responses to restrict virus infection and replication. Conversely, the role of EVs in the facilitation of virus spread and pathogenesis has been widely documented. Depending on the cell of origin, EVs carry effector functions from one cell to the other by horizontal transfer of their bioactive cargoes, including DNA, RNA, proteins, lipids, and metabolites. The diverse constituents of EVs can reflect the altered states of cells or tissues during virus infection, thereby offering a diagnostic readout. The exchanges of cellular and/or viral components by EVs can inform the therapeutic potential of EVs for infectious diseases. This review discusses recent advances of EVs to explore the complex roles of EVs during virus infection and their therapeutic potential, focusing on HIV-1.

Glycogen distribution of germ cells and Sertoli cells of seminiferous tubules in Jindo dog (진도견 정세관의 정세포와 Sertoli 세포내 glycogen의 분포)

  • Park, Young-seok;Lee, Seong-ho
    • Korean Journal of Veterinary Research
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    • v.36 no.3
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    • pp.521-529
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    • 1996
  • In an effort to obtain basic data of carbohydrate metabolism during spermiogenesis of the sexually-matured Jindo dog, the glycogen distribution in the testis was investigated by light and transmission electron microscopy. Periodic acid thiocarbohydrazide silver proteinate physical development(PA-TCH-SP-PD) staining method provided better results in the detection of glycogen granules from Sertoli cells and germ cells than the periodic acid schiff(PAS) staining method did. Pre-treatment of the tissue sections with ${\alpha}$-amylase elicited a significant decrease in PA-TCH-SP-PD stained granules, which suggested that the stained granules were of glycogen origin. High concentration of the glycogen granules were observed in the Sertoli cells, especially in its column, sheet-like processes, club-like processes, and tubular processes. The glycogen granules were unevenly distributed in some Sertoli cell columns. These results strongly indicated that the Sertoli cells of Jindo dogs showed vigorous activity of carbohydrate metabolism.

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Origin of Somatic Embryo Induced from Cotyledons of Zygotic Embryos at Various Developmental Stages of Ginseng

  • Soh, Woong-Young
    • Journal of Plant Biology
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    • v.37 no.3
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    • pp.365-370
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    • 1994
  • Excised cotyledon segments of ginseng zygotic embryos at various developmental stages were cultured on MS basal medium from which somatic embryos were directly induced. The frequency of somatic embryo formation on the segments declined with the advancing zygotic embryo maturity. All of the cells in the cotyledons of immature zygotic embryos were smaller and more densely cytoplasmic than those in mature embryos. Histological examinations revealed that the poly-somatic embryos formed on immature embryos were of multi-cell originand derived from the epidermal and subepidermal cell layers. However, in the cotyledon of germinating zygotic embryos, only theepidermal cells were densely cytoplasmic and singularly competent to develop into somatic embryos resulting into single embryos at a frequency of 100%.

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Synthesis of Lipophilic Benz[cd]indole Antifolates and Their Antitumor Activity In Vitro (지용성 Benz[cd]indole 엽산길항제의 합성 및 In Vitro 항암활성)

  • Baek Du-Jong
    • YAKHAK HOEJI
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    • v.49 no.1
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    • pp.60-67
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    • 2005
  • Nonclassical aminobenz[cd]indole antifolates 4, 5 and 6, in which the glutamic acid moiety of the classical antifolates is substituted by 2-phenylglycinamide or 3-aminobenzamide, were synthesized and their in vitro antitumor activity was evaluated. The purpose of this substitution is that the lipophilicity is enhanced due to the aromatic ring of the target compounds for the passive transport through lipid membrane of cells while the hydrogen bonding of the amide is retained in the active site of the enzyme, thymidylate synthase, where the glutamate is originally present. The target compounds were highly cytotoxic against tumor cell lines of murine and human origin with micromolar to nanomolar $IC_{50}$ values. Most effective was compound 4 ($N^6-methyl-N^6$-[4-[(${\alpha}$(S)-aminocarbonylbenzyl) aminocarbonyl]benzyl]-2,6-diaminobenz[cd]indole)with $IC_{50}$ of 2 nM against SW480, human colon adenocarcinoma cell line, which is 650-fold more potent than the reference compound 3.