• Title/Summary/Keyword: Immunosuppressive therapy

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Advanced T and Natural Killer Cell Therapy for Glioblastoma

  • Wan-Soo Yoon;Dong-Sup Chung
    • 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.

Regulation of NFAT Activation: a Potential Therapeutic Target for Immunosuppression

  • Lee, Mina;Park, Jungchan
    • Molecules and Cells
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    • v.22 no.1
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    • pp.1-7
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    • 2006
  • The NFAT family of transcription factors plays pivotal roles in the development and function of the immune system. Their activation process is tightly regulated by calcium-dependent phosphatase calcineurin and has been a target of the immunosuppressive drugs cyclosporin A and FK-506. Although the clinical use of these drugs has dramatically increased the success of organ transplantation, their therapeutic use is limited by severe side effects. Recent studies for the calcineurin/NFAT signaling pathway have identified a number of cellular proteins that inhibit calcineurin function. Specific peptide sequences that interfere with the interaction between calcineurin and NFAT have also been characterized. Moreover, diverse approaches to identify small organic molecules that modulate NFAT function have been performed. This review focuses on the recent advances in our understanding of the inhibitory modulation of NFAT function, which may open up the additional avenues for immunosuppressive therapy.

Importance of Accurate Diagnosis in Pyoderma Gangrenosum

  • Kim, Yoon Soo;Kim, Han Kyeol;Han, Yea Sik
    • Archives of Craniofacial Surgery
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    • v.15 no.3
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    • pp.138-141
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    • 2014
  • Pyoderma gangrenosum is a rare inflammatory reactive dermatosis marked by painful cutaneous ulcers. Diagnosis of pyoderma gangrenosum is usually made based on past medical history and after the exclusion of other possible diseases based on the clinical manifestations of the lesion. Diseases that show rapid progression to necrosis and that should not be misdiagnosed as pyoderma gangrenosum include malignant neoplasms and necrotizing fasciitis. Immunosuppressive agents such as steroids and cyclosporine are considered first-line therapy. Surgical removal of the necrotic tissues is contraindicated, as it may further induce immune reaction and promote ulcer to enlarge. Here, we present a case to encourage plastic surgeons to consider pyodermagangrenosum in the differential diagnosis of idiopathic ulcers. Satisfactory outcomes for patients with pyodermagangrenosum may be expected when using steroids and immunosuppressive agents during the early stage of the disease.

Acute Respiratory Distress Syndrome With Alveolar Hemorrhage due to Strongyloidiasis Hyperinfection in an Older Patient

  • Kim, Eun Jin
    • Annals of Geriatric Medicine and Research
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    • v.22 no.4
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    • pp.200-203
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    • 2018
  • Strongyloides stercoralis is an intestinal nematode that occurs sporadically in temperate areas like Korea. People who are in the immunosuppressed state, over the age of 65 or under the corticosteroid therapy are at risk for developing Strongyloides hyperinfection syndrome. Acute respiratory distress syndrome (ARDS) with alveolar hemorrhage is a rare presentation of Strongyloides hyperinfection. A 78-year-old man had been irregularly injected corticosteroid on his knees, but did not have any immunosuppressive disease. He was initially diagnosed with ARDS and septic shock. Bronchoalveolar lavage (BAL) fluid was bloody and its cytology revealed helminthic larvae identified as S. stercoralis. Results of Cytomegalovirus polymerase chain reaction (PCR), Pneumocystis jirovecii PCR, and Aspergillus antigen testing of the BAL fluid were positive. The clinical progress quickly deteriorated with multiple organ failure, shock and arrhythmia, so he finally died. This is a rare case of ARDS in an older patient without any known immunosuppressive conditions, with alveolar hemorrhage and S. stercoralis being found via BAL.

Candida albicans urinary tract infection in a Shih Tzu dog with immune-mediated hemolytic anemia

  • Jang, In-Sung;Yoon, Won-Kyoung;Hyun, Changbaig
    • Korean Journal of Veterinary Research
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    • v.57 no.2
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    • pp.139-141
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    • 2017
  • An 8-year-old castrated male Shih Tzu dog (weighing 7.0 kg) presented with anemia and lethargy. Initial diagnosis indicated immune-mediated hemolytic anemia. During therapy, a secondary urinary infection, probably due to the immune suppressive therapy, was diagnosed. Subsequent diagnostic tests, including urinalysis and urine culture, indicated candidal cystitis. Despite ketoconazole therapy for candidal cystitis, the dog died suddenly. A Candida albicans infection was confirmed upon postmortem evaluation. Prolonged immunosuppressive therapy might be the cause of this infection. This is the first case report describing a Candida albicans urinary tract infection accompanied by hemolytic anemia in a dog in Korea.

Combination therapy of cyclosporine and prednisolone in a dog with systemic lupus erythematosus

  • Kim, Yeon-Hee;Kang, Min-Hee;Park, Hee-Myung
    • Korean Journal of Veterinary Research
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    • v.56 no.1
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    • pp.47-49
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    • 2016
  • An 11-year-old, spayed female poodle presented with fever and shifting lameness. Physical examination revealed hyperthermia ($40.6^{\circ}C$), and proteinuria was detected upon urinalysis. Increased neutrophils (83%) and decreased viscosity were revealed upon synovial fluid analysis. Serum antinuclear antibody was positive at 1 : 80. Based on these findings, the dog was diagnosed with systemic lupus erythematosus. Immunosuppressive therapy was initiated with prednisolone and cyclosporine, and the condition was markedly improved after the treatments. This case report describes the clinical and laboratory findings, imaging characteristics and successful outcomes after prednisolone plus cyclosporine therapy in a canine systemic lupus erythematosus case.

Strongyloidiasis associated with amebiasis and giardiaisis in an immunocompetent boy presented with acute abdomen

  • Dinleyici, Ener-Cagry;Dogan, Nihal;Ucar, Birsen;Ilhan, Huseyin
    • Parasites, Hosts and Diseases
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    • v.41 no.4
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    • pp.239-242
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    • 2003
  • Strongyloides stercoralis (SS) is an intestinal nematode that is mainly endemic in tropical and subtropical regions and sporadic in temperate zones. SS infection frequently occurs in people who have hematologic malignancies, HIV infection and in individuals undergoing immunosuppressive therapy. In this study, we report a 12year-old immunocompetent boy who was admitted to our hospital with acute abdomen. Laboratory evaluation showed strongyloidiasis, amebiasis and giardiasis. Clinical and laboratory findings immediately improved with albendazole therapy. Therefore, when diarrhea with signs of acute abdomen is observed, stool examinations should be done for enteroparasitosis. This approach will prevent misdiagnosis as acute abdomen. Complete clinical improvement is possible by medical therapy without surgical intervention.

A Case of Idiopathic Thrombocytopenic Purpura in Pregnancy (임신과 동반된 특발성 혈소판 감소성 자반증 1례)

  • Kim, Mi-Sook;HwangBo, Ho-Joon;Lee, Young-Gi;Park, Yoon-Kee;Lee, Sung-Ho
    • Journal of Yeungnam Medical Science
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    • v.10 no.2
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    • pp.512-517
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    • 1993
  • Idiopathic thrombocytopenic purpura is an uncommon illness but most common form of thrombocytopenia in pregnancy. Corticosteroids, splenectomy, immunosuppressive drugs, and immunoglobulin therapy have been recommended for management. The optimal method of delivery is controversial. We have experienced a case of idiopathic thrombocytopenic purpura diagnosed previously and managed with corticosteroid and vincristine, which was followed by pregnancy, vaginal delivery and postpartum splenectomy.

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Anti-inflammatory Effects of UDCA on Splenocytes Exposed to PMA/Ionomycin

  • Park, So-Young;Woo, Jong-Shick;Jung, Yu-Jin;Won, Tae-Joon;Hih, Yun-Ju;Lee, Chan-Woo;Kim, Hyo-Shin;Joo, Seong-Soo;Lee, Do-Ik;Hwang, Kwang-Woo
    • 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.

A Case of Posttransplant Lymphoproliferative Disease Following Renal Transplantation in a Child (소아에서 신장 이식 후 발생한 Posttransplant Lymphoproliferative Disease 1례)

  • Jhang Won-Kyoung;Hahn Hye-Won;Lee Mee-Jeung;Ghim Thad-T.;Park Young-Seo
    • Childhood Kidney Diseases
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    • v.7 no.2
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    • pp.245-252
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    • 2003
  • Posttransplant lymphoproliferative disease(PTLD) has emerged as a potential life-threatening complication of immunosuppressive therapy after organ transplantation. The occurrence of PTLD is usually associated with an Epstein-Barr virus(EBV) infection in patients who are treated by aggressive immunosuppressive therapy. PTLD is represented by diverse manifestations ranging from reactive lymphoid hyperplasia to high grade malignant lymphoma. This is a case report of a late PTLD in a child. The patient is a 14-year-old girl, who presented as malignant lymphoma 44 months after successful renal transplantation. There was no evidence of EBV infection. On bone marrow study, many neoplastic lymphoid cells were defected. Aggressive chemotherapy for PTLD had resulted in clinical remission. However the patient expired from uncontrolled sepsis and septic shock after 77 days.

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