• Journal of Korean Neurosurgical Society
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• v.66 no.4
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• pp.356-381
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• 2023

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the blood-brain-barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versus-host disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.215-223
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• 1999

Background: The replacement of the narrowed long-segment trachea with various prosthetic materials or tissue grafts remains a difficult and unsolved surgical problem. Homologous cryopreserved tracheal transplantation has been considered to treat the irreversibly-damaged organs, such as in the lung or heart transplantation and also to overcome the limited supply of donor organs. We examined the morphological changes and the immunosuppressive effects of the cryopreserved trachea after the heterotopic transplantation in the rats. Material and Method: Sixty tracheal segments harvested from 30 donor Wistar rats were heterotopically implanted into the peritoneal cavity of 20 recipient Wistar rats and 40 Sprague Dawley rats. The 60 recipient rats were divided into 6 groups(10 rats/ group). In groups I, II, and III, 30 tracheal segments were implanted immediately after the harvesting and in groups IV, V, and VI, the segments were implanted 28 days after the cryopreservation. Groups I and IV were Wistar syngeneic controls. Groups II and V were Sprague Dawley recipients receiving no immunosuppression and Groups III and VI, were Sprague Dawley recipients receiving immunosuppressive agents. At 28 days all rats were sacrificed and the tracheal segments were evaluated grossly and histologically. Result: Immunosuppression of the tracheal segments had a significant influence on the changes of the tracheal lumen and tracheal epithelial cells, irrespective of the cryopreservation of the trachea(p<0.001). In groups III and VI receiving immunosuppressive agents, the tracheal lumen was patent and the normal epithelial cells were observed, however in the other groups not receiving the immunosuppressive agents, there were almost luminal obliteration by the proliferation of the fibrous tissues and a loss of the epithelial cells, the findings were similar to those in the case of obliterative bronchiolitis after a lung and a heart-lung transplantation. Conclusion: With the appropriate immunosuppressive agents, the lumen and the respiratory epithelium of the transplanted tracheal segment were well preserved, even after the cryopreservation of the tracheal segment, which shows the possibility of the long-term preservation and homologous transplantation of the trachea. But fibroproliferative obliteration of the tracheal lumen and the loss of the normal respiratory epithelial cells, characteristic findings of obliterative bronchiolitis, were observed in the groups without the immunosuppression. This experiment using the rat trachea may be useful in studying the pathogenesis, treatment, and prevention of obliterative bronchiolitis after a lung and a heart-lung transplantation.

• Journal of fish pathology
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• v.5 no.2
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• pp.77-85
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• 1992

This study was carried out in order to investigate the immunosuppressive factor and immune response of color carp. The protection and serum antibody production of juvenile color carp aganist Aeromonas hydrophila were investigated on the effect of temperature differences and injected several aquatic drugs, i.e. Hydrocortisone, Oxytetracycline, Chloramphenicol and Ascorbic acid. The fish were injected intraperitoneally with 1mg/fish of HKC and FKC at three different temperature conditions as $16^{\circ}C$, $24^{\circ}C$, and $32^{\circ}C$ respectively. There were induced better protection and serum antibody production in the fish which had been kept at $24^{\circ}C$ than in the fish which had been kept at $16^{\circ}C$ and $32^{\circ}C$. The FKC immunized fish were followed 24 hrs later with intraperitoneal injection of 40mg/kg body weight of Hydrocortisone, 60mg/kg body weight of Oxytetracycline. 60mg/kg body weight of Chloramphenicol and 30mg/kg body weight of Ascorbic acid, respectively. The control fish were injected PBS only. The fish given the above aquatic drugs reduced serum antibody production level and protection rate when compared to control fish. As the results, immune response of juvenile color carp immunized FKC at $24^{\circ}C$ was more effective than $16^{\circ}C$ or $32^{\circ}C$ and immune response of juvenile color carp injected several aquatic drugs which was seemed to be immunosuppressive factor.

• Korean journal of applied entomology
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• v.51 no.3
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• pp.245-253
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• 2012

Benzylinedeneacetone (BZA) is a bacterial metabolite which is synthesized by at least two entomopathogenic bacteria, namely Xenorhabdus nematophila and Photorhabdus temperata subsp. temperata. It has been shown to possess inhibitory effects on insect cellular and humoral immune responses as well as antimicrobial activities against various species of bacteria and fungi. However, its relatively high phytotoxicity, and nonsystematic effect have thus far prevented its development into an optimal pesticide. This study screened five different BZA derivatives in order to select an optimal compound, which would have relatively high solubility and low phytotoxicity while retaining sufficient degrees of the immunosuppressive and antimicrobial activities associated with BZA. Hydroxylation of the benzene ring of BZA was found to significantly suppress its immunosuppressive and antimicrobial activities. Transformation of the ketone of BZA by carboxylation also suppressed the inhibitory activities. However, a shortening of the aliphatic chain of BZA into acetate form (4-hydroxyphenylacetic acid: HPA) did not decrease the inhibitory activity. HPA also showed much less phytotoxicity against the hot pepper plant Capsicum annuum, when compared to BZA. This study identified an optimal BZA derivative, which exhibited relatively little phytotoxicity, but retained a high degree of inhibitory activity to suppress insect immune responses and antimicrobial activities against plant pathogens.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.181-184
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• 2009

Immune-mediated hemolytic anemia(IMHA) is one of the most common causes of anemia in small animals and immune-mediate thrombocytopenia(IMT) is also an immune mediated disease that affects small animals. The initial treatment for IMHA and IMT is medical suppression of the immune system with glucocorticoids and other immunosuppressive drugs. However, even with appropriate treatments, some animals are not responsive to the treatment and may need further immunosuppressive therapies or some alternative medicines. An eight-year-old spayed female Siamese cat with IMHA and an eight-year-old castrated male King Charles Spaniel dog with IMT were referred to the traditional medical service of the veterinary medical center. Both animals were unresponsive to steroids or other immunosuppressive treatments. Gui-Pi-Tang, one of the traditional herbal medicines, was administered to the animals. After 1-month of Gui-Pi-Tang administration, the packed cell volume(PCV) of the cat and platelets count of the dog had showed remarkable improvement. After four months of follow up in the cat, and 18 months of follow up in the dog, the improved PCV and platelet counts of the animals were maintained normally. Therefore, Gui-Pi-Tang might be considered as an alternative treatment in small animals with immune-mediated blood disorders.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.2
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• pp.115-122
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• 1998

The maintenance of a viable pregnancy has long been viewed as an immunological paradox. The deveolping embryo and trophoblast are immunologically foreign to the maternal immune system due to their maternally inherited genes products and tissue-specific differentiation antigens (Hill & Anderson, 1988). Therefore, speculation has arisen that spontaneous abortion may be caused by impaired maternal immune tolerance to the semiallogenic conceptus (Hill, 1990). Loss of recall antigen has been reported in immunosuppressed transplant recipients and is associated with graft survival (Muluk et al., 1991; Schulik et al., 1994). Progesterone $(10^{-5}M)$ has immunosuppressive capabilities (Szekeres-Bartho et al., 1985). Previous study showed that fertile women, but not women with unexplained recurrent abortion (URA), lose their immune response to recall antigens when pregnant (Bermas & Hill, 1997). Therefore, we hypothesized that immunosuppressive doses of progesterone may affect proliferative response of lymphocytes to trophoblast antigen and alloantigen. Proliferative responses using $^3H$-thymidine ($^3H$-TdR) incorporation of peripheral blood mononuclear cells (PBMCs) to the irradiated allogeneic periperal blood mononuclear cells as alloantigen, trophoblast extract and Flu as recall antigen, and PHA as mitogen were serially checked in 9 women who had experienced unexplained recurrent miscarriage. Progesterone vaginal suppositories (100mg b.i.d; Utrogestan, Organon) beginning 3 days after ovulation were given to 9 women with unexplained RSA who had prior evidence of Th1 immunity to trophoblast. We checked proliferation responses to conception cycle before and after progesterone supplementation once a week through the first 7 weeks of pregnancy. All patients of alloantigen and PHA had a positive proliferation response that occmed in the baseline phase. But 4 out of 9 patients (44.4%) of trophoblast antigen and Flu antigen had a positive proliferative response. The suppression of proliferation response to each antigen were started after proliferative phase and during pregnancy cycles. Our data demonstrated that since in vivo progesterone treated PBMCs suppressed more T-lymphocyte activation and $^3H$-TdR incorporation compare to PBMCs, which are not influenced by progesterone. This data suggested that it might be influenced by immunosuppressive effect of progesterone. In conclusion, progesterone may play an important immunological role in regulating local immune response in the fetal-placental unit. Furthermore, in the 9 women given progesterone during a conception cycle, Only two (22%) repeat pregnancy losses occured in these 9 women despite loss of antigen responsiveness (one chemical pregnancy loss and one loss at 8 weeks of growth which was karyotyped as a Trisomy 4). These finding suggested that pregnancy loss due to fetal aneuploidy is not associated with immunological phenomena.

• Journal of Veterinary Clinics
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• v.25 no.5
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• pp.415-419
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• 2008

The purpose of this study was to determine clinical features of canine episcleritis and outcomes of therapy in Korea. The medical records of dogs with episcleritis presented at the Veterinary Medical Teaching Hospital of Seoul National University from January 2006 to December 2007 were reviewed. Episcleritis was diagnosed in 17 eyes of 12 dogs. The most frequently affected breed was Shih Tzu (n = 6). The median affected age was 5 years with a range from 3 years to 12 years. Simple episcleritis was identified in 8 dogs, nodular granulomatous episcleritis (NGE) in 3 dogs, and secondary episcleritis caused by panophthalmitis in a dog. The combination immunosuppressive therapy of topical corticosteroids, topical cyclosporine A, and intralesional injection of triamcinolone (4 mg) and gentamicin (4 mg) was performed. Most of the patients with episcleritis were resolved within 30 days following the therapy. Surgical excision was performed in 1 NGE case which was not responded to the medical therapy. Recurrence was observed in 4 dogs between 5 and 8 months after the first visit. It is considered that strong immunosuppressive therapy and periodic ocular examination are needed to control episcleritis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.247-247
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• 1994

Acteoside는 일명 Verbascoside로 불리우는 Phenylpropanoid glycoside에 속하는 화합물로 이미 보고되어진 생리활성으로는 Cytotoxic effect, Anti bacterial effect, Immunosuppressive effect, C-AMP Phospaestrase의 저해활성등 여러가지 생리활성이 보고되어 있다. 저자등은 마주송이풀의 성분을 규명하는 가운데 acteoside가 주성분임을 확인하게 되었고 이 식물이 한의서에서 관절염등에 사용되어 진다는 점에서 소염활성을, 식물을 건조할때 흑색으로 변하는데 착안하여 iridoid glycoside의 존재가 추정되어 iridoid glycoside의 일반 생리활성인 담즙분비 촉진작용과 간장보호 작용을 검색하던 중 phenylpropanoid glycoside인 acteoside에서도 담즙분비촉진 작용과 간장보호작용의 지견을 얻었기에 보고하고자 한다.

• YAKHAK HOEJI
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• v.29 no.2
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• pp.55-61
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• 1985

The effect of dietary fat on the immunotoxicity of chloramphenicol was investigated in mice, sensitized and challenged with sheep red blood cells. Chloramphenicol suppressed more cell-mediated immunity than humoral immunity. The saturated fat diet elevated humoral and cell-mediated immunotoxicity, whereas the unsaturated fat diet decreased humoral immunotoxicity, but elevated cell-mediated immunotoxicity of chloramphenicol. Especially, the normal diet in saturated and unsaturated fat restored immunosuppressive effect of chloramphenicol compared to the saturated fat diet and the unsaturated fat diet.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.