Biomedical subjects

Chang-Hyun Kim

Publications and source records attributed to Chang-Hyun Kim.

10 recordsLinked to original sources

PubMed2006

Direct vaccination with pseudotype baculovirus expressing murine telomerase induces anti-tumor immunity comparable with RNA-electroporated dendritic cells in a murine glioma model.

Baculovirus pseudotyped with vesicular stomatitis virus G protein (Bac-VSV-G) was found to efficiently transduce and express transgenes on mammalian cells. In this study, this recombinant virus was used for induction of anti-tumor immunity against murine telomerase reverse transcriptase (mTERT) and was compared with RNA-electroporated dendritic cells (DCs) in a murine glioma model. Splenocytes from the mice vaccinated with Bac-VSV-G expressing mTERT (Bac-VSVG-mTERT) showed significantly increased numbers of mTERT-specific IFN-gamma-secreting T cells using an ELISPOT technique, and also showed increased NK cell activity. In addition, the TERT-specific T cells activated by Bac-VSVG-mTERT and mTERT RNA-electroporated DCs were predominantly CD4+ T cells and CD8+ T cells, respectively. The protective anti-tumor effect of Bac-VSVG-mTERT was similar to that of mTERT RNA-electroporated DCs. These results suggest that the pseudotype baculovirus expressing TERT may be a good candidate for a genetic vaccine for use in the treatment of malignant gliomas.

Animals↗

PubMed2006

Enhancement of anti-tumor immunity specific to murine glioma by vaccination with tumor cell lysate-pulsed dendritic cells engineered to produce interleukin-12.

AIM: The aim of this study was to develop an immunotherapy specific to a malignant glioma by examining the efficacy of glioma tumor-specific cytotoxic T lymphocytes (CTL) as well as the anti-tumor immunity by vaccination with dendritic cells (DC) engineered to express murine IL-12 using adenovirus-mediated gene transfer and pulsed with a GL26 glioma cell lysate (AdVIL-12/DC+GL26) was investigated. EXPERIMENT1: For measuring CTL activity, splenocytes were harvested from the mice immunized with AdVIL-12/DC+GL26 and restimulated with syngeneic GL26 for 7 days. The frequencies of antigen-specific cytokine-secreting T cell were determined with mIFN-gamma ELISPOT. The cytotoxicity of CTL was assessed in a standard 51Cr-release assay. For the protective study in the subcutaneous tumor model, the mice were vaccinated subcutaneously (s.c) with 1x10(6) AdVIL-12/DC+GL26 in the right flanks on day -21, -14 and -7. On day 7, the mice were challenged with 1x10(6) GL26 tumor cells in the shaved left flank. For a protective study in the intracranial tumor model, the mice were vaccinated with 1x10(6) AdVIL-12/DC+GL26 s.c in the right flanks on days -21, -14 and -7. Fresh 1x10(4) GL26 cells were inoculated into the brain on day 0. To prove a therapeutic benefit in established tumors, subcutaneous or intracranial GL26 tumor-bearing mice were vaccinated s.c with 1x10(6) AdVIL-12/DC+GL26 on day 5, 12 and 19 after tumor cell inoculation. RESULTS: Splenocytes from the mice vaccinated with the AdVIL-12/DC+GL26 showed enhanced induction of tumor-specific CTL and increased numbers of IFN-gamma: secreting T cells by ELISPOT. Moreover, vaccination of AdVIL-12/DC+GL26 enhanced the induction of anti-tumor immunity in both the subcutaneous and intracranial tumor models. CONCLUSIONS: These preclinical model results suggest that DC engineered to express IL-12 and pulsed with a tumor lysate could be used in a possible immunotherapeutic strategy for malignant glioma.

Animals↗

PubMed2006

Dendritic cells transduced with recombinant adenoviruses induce more efficient anti-tumor immunity than dendritic cells pulsed with peptide.

Transduction with recombinant, replication-defective adenovirus (AdV) vectors encoding a transgene is an efficient method for gene transfer into murine or human dendritic cells (DC). We previously reported that human dendritic cells transduced with recombinant adenovirus encoding the CEA gene (AdVCEA) can effectively induce antigen-specific cytotoxic T lymphocytes (CTL) in vitro. In this study, the efficacy of vaccination using AdVCEA-transduced DC was compared with peptide-pulsed DC in terms of the antigen-specific CTL activity and anti-tumor immunity to MC38/CEA2 in a murine tumor model. AdVCEA-transduced DC increased antigen-specific T-cell proliferation, augmented the number of IFN-gamma secreting T-cells and induced potent CEA-specific CTL capable of lysing target cells pulsed with CEA peptide, as well as MC38/CEA2 expressing CEA, compared to peptide-pulsed DC. Moreover, vaccination of mice with AdVCEA-transduced DC induced a potent protective and therapeutic anti-tumor immunity to MC38/CEA2 in a subcutaneous model. These data suggest that AdVCEA-transduced DC appears to be superior to peptide-pulsed DC for the induction of anti-tumor immunity against tumor cells; this occurs through augmentation of the antigen-specific CTL response and may be used as an efficient DC-based tumor vaccine applicable to clinical care.

Adenoviridae↗

PubMed2006

Evolving compact and interpretable Takagi-Sugeno fuzzy models with a new encoding scheme.

Developing Takagi-Sugeno fuzzy models by evolutionary algorithms mainly requires three factors: an encoding scheme, an evaluation method, and appropriate evolutionary operations. At the same time, these three factors should be designed so that they can consider three important aspects of fuzzy modeling: modeling accuracy, compactness, and interpretability. This paper proposes a new evolutionary algorithm that fulfills such requirements and solves fuzzy modeling problems. Two major ideas proposed in this paper lie in a new encoding scheme and a new fitness function, respectively. The proposed encoding scheme consists of three chromosomes, one of which uses unique chained possibilistic representation of rule structure. The proposed encoding scheme can achieve simultaneous optimization of parameters of antecedent membership functions and rule structures with the new fitness function developed in this paper. The proposed fitness function consists of five functions that consider three evaluation criteria in fuzzy modeling problems. The proposed fitness function guides evolutionary search direction so that the proposed algorithm can find more accurate compact fuzzy models with interpretable antecedent membership functions. Several evolutionary operators that are appropriate for the proposed encoding scheme are carefully designed. Simulation results on three modeling problems show that the proposed encoding scheme and the proposed fitness functions are effective in finding accurate, compact, and interpretable Takagi-Sugeno fuzzy models. From the simulation results, it is shown that the proposed algorithm can successfully find fuzzy models that approximate the given unknown function accurately with a compact number of fuzzy rules and membership functions. At the same time, the fuzzy models use interpretable antecedent membership functions, which are helpful in understanding the underlying behavior of the obtained fuzzy models.

Algorithms↗

PubMed2004

Surgical procedure "simplified retrosigmoid approach" for C-P angle lesions.

Previously, we reported surgical results of the simplified retrosigmoid approach for vestibular nerve sectioning in the cases with intractable vertigo. Here, we introduce in details surgical procedures of the simplified retrosigmoid (also called "subasterional" here for simplification) approach developed by one of the authors (J.H.L.). This approach is to operate cerebello-pontine (C-P) angle lesions through a small upper lateral window below the transverse-sigmoid junction. The retroauricular 4-5 cm skin incision, triangular craniectomy 2 cm in width, dural opening and closure, special considerations, and reconstruction of the skull defect were outlined. The bony landmarks for triangle craniectomy below asterion were described in detail. The C-P angle was appropriately approached for microvascular decompression, removal of C-P angle tumors, and vestibular nerve resection. This subasterional approach was characterized by short operation time of 1-3 h and less postoperative discomforts compared to the conventional retrosigmoid approach.

Cerebellar Diseases↗

PubMed2004

CpG-ODN-stimulated dendritic cells act as a potent adjuvant for E7 protein delivery to induce antigen-specific antitumour immunity in a HPV 16 E7-associated animal tumour model.

We previously reported that both E7 and CpG-oligodeoxynucleotide (ODN) are required for protecting animals from human papillomavirus (HPV) 16 E7-associated tumour challenge. Here we investigate dendritic cells (DC)-based approach in this protection. In the study, we isolated bone marrow-derived DC and stimulated DC with E7 and ODN. In vitro stimulation of DC with E7 plus ODN resulted in more production of interleukin-12, as compared to that with E7 or ODN alone. Further injection with E7+ODN-stimulated DC resulted in more significant tumour protection, as compared to stimulation with E7 or ODN alone. We further evaluated the levels of immune responses induced by DC stimulated with E7+ODN. We observed little enhancement of E7-specific antibody and T helper cell proliferative responses by E7+ODN stimulation, as compared to E7 stimulation. However, there was some enhancement of interferon-gamma (IFN-gamma) production from CD4+ T cells and a more significant production of IFN-gamma from CD8+ T cells by E7+ODN stimulation, as compared to E7 stimulation alone. This was consistent with intracellular IFN-gamma staining levels of CD8+ T cells. Tumour protection further appeared to be mediated by CD8+ T cells, as determined by in vivo T-cell depletion. Thus, these data suggest that upon ODN stimulation DC might function as a potent adjuvant for E7 protein delivery for induction of protective cellular immunity against HPV E7-associated tumour challenge.

Adjuvants, Immunologic↗

PubMed2003

Management of surgical clinoidal meningiomas.

OBJECT: Clinoidal meningiomas remain a major neurosurgical challenge. Surgery-related outcome has been less than desirable in the past, and little attention has been directed toward improving visual deficits. The authors advocate a skull base technique for the removal of these difficult tumors and describe its advantages in terms of improving extent of resection and enhancing overall outcome, particularly visual function. METHODS: A retrospective analysis was performed on data obtained in 26 consecutive patients with clinoidal meningiomas (including one patient with hemangiopericytoma) who underwent resection between June 1995 and January 2003. In 24 cases the skull base procedure involved extradural anterior clinoidectomy, optic canal unroofing, and optic sheath opening; in two cases a standard pterional craniotomy was performed. Fourteen of the 26 patients suffered significant preoperative visual deficits. All patients underwent thorough pre- and postoperative ophthalmological evaluations. The follow-up period ranged from 3 to 91 months (mean 42.3 months). Total resection was achieved in 20 patients (77%), and the majority (76.9%) of patients with preoperative visual impairment experienced significant improvement. CONCLUSIONS: With the use of the skull base technique, total resection and excellent visual outcome may be achieved with minimal morbidity in most patients with clinoidal meningiomas.

Adolescent↗

PubMed2003

Verification by polymerase chain reaction of vertical transmission of Theileria sergenti in cows.

To evaluate the transplacental transfer of Theileria sergenti infection in cattle, we used DNA probes to detect T. sergenti in 6 pregnant cows and their calves. All the animals were monitored by parasitologic, serologic, and polymerase chain reaction (PCR) assays for a predicted 875-base-pair (bp) DNA product and a 684-bp amplicon detected by nested PCR in the blood and spleens of aborted fetuses. An open reading frame (ORF) starting at nucleotide 170 and terminating at position 1021 was shown to code for a polypeptide of 283 amino acid residues. All 6 dams and 5 calves were positive for T. sergenti in all tests. One calf was positive only with nested PCR. We conclude that transplacental transmission of T. sergenti is a significant problem. The relevance of the data in the programmed introduction of new (especially pregnant) animals into established clean herds needs serious consideration with regard to control of theileriosis and other tickborne diseases.

Animals↗

PubMedDate not supplied

Differential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells.

BACKGROUND: The amino acid transport system L is a major nutrient transport system responsible for Na(+)-independent transport of neutral amino acids, including several essential amino acids. The system L is divided into two major subgroups, the L-type amino acid transporter 1 (LAT1) and the L-type amino acid transporter 2 (LAT2). In malignant tumors, the LAT1 is highly expressed to support tumor cell growth. In the present study, the expressions and functions of the system L amino acid transporters were examined and compared in both FOB human osteoblast cells and Saos2 human osteogenic sarcoma cells. MATERIALS AND METHODS: The expressions and functions of the system L amino acid transporters in both FOB and Saos2 cells were examined using RT-PCR, Western blot analysis and amino acid transport measurement. RESULTS: RT-PCR and Western blot analysis revealed that the FOB and Saos2 cells expressed LAT1 and LAT2, together with their associated protein 4F2hc, but the expression of LAT2 in the Saos2 cells was very weak. The uptakes of [14C]L-leucine by FOB and Saos2 cells were Na(+)-independent and were completely inhibited by the system L selective inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). The affinity and the inhibition profiles of [14C]L-leucine uptake by various amino acids in the FOB and Saos2 cells were comparable with those for the LAT2 and LAT1 expressed in Xenopus oocytes, respectively. The majority of [14C]L-leucine uptake is, therefore, mediated by LAT2 and LAT1 in FOB and Saos2 cells, respectively. CONCLUSION: These results suggest that the transport of neutral amino acids, including several essential amino acids into the FOB and Saos2 cells, are mainly mediated by LAT2 and LAT1, respectively. Moreover, the specific inhibition of LAT1 in tumor cells might be a new rationale for antitumor therapy.

Amino Acid Transport System L↗

PubMedDate not supplied

The RNA interference of amino acid transporter LAT1 inhibits the growth of KB human oral cancer cells.

BACKGROUND: Amino acid transporters are essential for growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the Na+-independent transport of neutral amino acids, including several essential amino acids. The L-type amino acid transporter 1 (LAT1) is overexpressed to support cell growth in malignant tumors. Double-stranded RNA-mediated RNA interference (RNAi) analysis can be used in a wide variety of eukaryotes to induce the sequence-specific inhibition of gene expression. The current study attempted to investigate the effects of silencing LAT1 expression with small interfering RNA (siRNA) on cell growth in the KB human oral squamous cell carcinoma. MATERIALS AND METHODS: The effects of silencing LAT1 expression with siRNA KB on cell growth were examined using RT-PCR, Western blot analysis, amino acid transport measurement and the MTT assay. RESULTS: In the RT-PCR and Western blot analyses, the siRNA of LAT1 inhibited the expressions of LAT1 mRNA and protein. The uptake of [14C]L-leucine was also inhibited by the siRNA of LAT1. In the MTT assay, the siRNA of LAT1 inhibited the growth of the KB cells in a time-dependent manner, indicating that this growth inhibition was induced by the LAT1-mediated blocking of neutral amino acid transport. CONCLUSION: The transport of neutral amino acids, including several essential amino acids, into the KB human oral squamous cell carcinoma is mainly mediated by LAT1. Furthermore, LAT1 could be a new target for the inhibition of cancer cell growth.

Carbon Radioisotopes↗