Biomedical subjects

Seok-Gu Kang

Publications and source records attributed to Seok-Gu Kang.

11 recordsLinked to original sources

PubMed2026

Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.

Glioblastoma (GBM) remains lethal despite maximal therapy. The adult subventricular zone (SVZ), a neural stem-cell niche, has been implicated as a potential site of origin, yet the identity and functional properties of putative GBM origin-like cells (GBM-OCs) within the SVZ remain unclear. An SVZ-restricted somatic mutation mouse model (Cre-induced EGFRvIII expression with Trp53 and Pten disruption) was established and mouse SVZ-derived cells were prospectively isolated for functional and molecular profiling. Self-renewal, multipotency, invasive potential and tumour-initiating capacity were assessed relative to control SVZ cells and matched tumour-derived tumourspheres. Whole-genome and RNA sequencing defined genomic and transcriptional alterations during early progression. Mouse GBM-OCs exhibited self-renewal and multilineage differentiation and initiated tumours only after re-implantation into the SVZ (11/29, 38%), whereas direct striatal implantation failed (0/25, 0%), indicating context-dependent tumorigenic potential associated with the SVZ microenvironment. In contrast, tumour-derived tumourspheres retained tumorigenic capacity upon implantation into both the SVZ and the striatum. During progression from mouse GBM-OCs to tumours, whole-chromosome and arm-level aneuploidies accumulated. In patients with GBM, multi-region single-nucleus RNA sequencing of tumour-free SVZ, matched tumours and tumour-free cortex identified rare neural stem cell-like, astrocyte-like and oligodendrocyte precursor-like SVZ populations transcriptionally aligned with GBM programmes. These cells showed single-nucleus RNA-inferred chromosome 7 gain and/or chromosome 10 loss signals, with concordant low-frequency copy-number alterations in the SVZ detected by exome sequencing and enriched in matched tumours. Together, these findings support the presence of SVZ-resident stem or progenitor-like populations with early GBM-associated features, consistent with putative GBM-OCs, and highlight the SVZ niche as a potential target for early detection and niche-informed therapeutic strategies.

Animals↗

PubMed2006

Surgical results in pediatric moyamoya disease: angiographic revascularization and the clinical results.

OBJECTIVE: We retrospectively reviewed the pediatric patients with moyamoya disease (MMD) who underwent bypass surgery at our institution to compare the surgical results according to the surgical procedures. PATIENTS AND METHODS: There were 24 total patients (age range: 2-15 years; mean age: 8.2 years). Twelve patients underwent encephalo-duro-arterio-synangiosis (EDAS) on 16 sides, 5 patients underwent encephalo-duro-arterio-myo-synangiosis (EDAMS) on 8 sides and 7 patients underwent combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with EDAMS (STA-MCA-EDAMS) on 12 sides. The postoperative results were evaluated between 4 months and 5 years following surgery in terms of the angiographic revascularization and the clinical outcome. RESULTS: EDAMS, regardless of the combined STA-MCA anastomosis, was significantly effective for achieving a good extent of the postoperative angiographic revascularization as compared with simple EDAS (P<0.05). STA-MCA-EDAMS tended to be better with respective to the relief of preoperative ischemic symptoms as compared with simple EDAS, although there was no significant statistical difference. CONCLUSION: These results suggest that EDAMS with or without the combination of STA-MCA anastomosis was very useful for the formation of collateral circulation in comparison with simple EDAS for treating the pediatric patients with MMD, although these findings were not well correlated with the clinical outcomes.

Adolescent↗

PubMed2006

Multiple stem cell traits of expanded rat bone marrow stromal cells.

Bone marrow stromal cells (BMSC) exhibit many traits of a stem cell population. Knowing that BMSC have the ability to self-renew, proliferate and differentiate into a variety of cell types, questions may arise as to whether these traits differ between the cells that have different expansion times. In this study, we examined the stem cell potentiality of BMSC through their characterization, proliferative capacity and the ability to differentiate into multiple lineages in the cultured 2nd passage cells and 10th passage cells. The results were as follows: (1) the 10th passage cells had a larger and more flatted morphology than the 2nd passage cells and also exhibited a decreased labeling for BMSC-related antigens such as CD90, CD73. (2) The cell proliferative capacity was approximately 2 times greater in the 2nd passage cells, and the apoptosis phenomenon was detected in the 10th passage cells. (3) The ability to differentiate into mesodermal tissue (osteocytes, adipocytes), as well as into ectodermal tissue (neurons) was more effective in the 2nd passage cells. Taken together, early stage BMSC would be a valuable cell source for various in vitro applications, as well as cell therapy.

Animals↗

PubMed2006

Combined direct anastomosis and encephaloduroarteriogaleosynangiosis using inverted superficial temporal artery-galeal flap and superficial temporal artery-galeal pedicle in adult moyamoya disease.

BACKGROUND: We evaluated the efficacy of combined STA-MCA anastomosis and EDAGS using inverted STAGF and STAGP for the treatment of adult MMD. METHODS: This study included 8 patients with nonhemorrhagic MMD. There were 6 women and 2 men who were between 23 and 62 years old (mean = 37.8 years) in the sample. The combined surgery was performed on 12 sides in the 8 patients. The surgical results were assessed for clinical outcome, angiographic revascularization, and hemodynamic change on HMPAO brain SPECT. The follow-up period ranged from 6 to 62 months (mean = 27 months). RESULTS: Clinical symptoms and signs were improved or stabilized, and the extent of revascularization evident on external carotid angiograms was excellent in all 8 patients. The CBF on HMPAO SPECT also improved in all 12 sides that were operated on with the combined surgery, except for the preexisting infarcted area, on the basal as well as Diamox stimulation studies. One patient had a transient speech disturbance after surgery, and another patient had delayed wound healing. CONCLUSIONS: The combined STA-MCA anastomosis and EDAGS using inverted STAGF/P seems to be one of the most effective surgical modalities for the treatment of nonhemorrhagic MMD in adults.

Adult↗

PubMed2006

Coexisting intracranial meningeal melanocytoma, dermoid tumor, and Dandy-Walker cyst in a patient with neurocutaneous melanosis. Case report.

Neurocutaneous melanosis (NCM) associated with Dandy-Walker malformation is a very rare congenital neurodysplasia with the same origin. Primary intracranial melanocytic and dermoid tumors are also benign congenital lesions that usually arise from the leptomeninges and are formed by the inclusion of cutaneous ectoderm at the time of neural tube closure. The authors describe a patient with coexisting intracranial meningeal melanocytoma, NCM with Dandy-Walker malformation, and intraventricular dermoid tumor.

Adult↗

PubMed2006

Diagnostic method for differentiating external hydrocephalus from simple subdural hygroma.

OBJECT: The various terms used to describe subdural fluid collection--"external hydrocephalus", "subdural hygroma", "subdural effusion", "benign subdural collection", and "extraventricular obstructive hydrocephalus"-reflect the confusion surrounding the diagnoses of these diseases. Differentiating external hydrocephalus from simple subdural hygroma may be difficult, but the former appears to be a distinct clinical entity separate from the latter. In this report, the authors present a diagnostic method for differentiating external hydrocephalus from simple subdural hygroma, based on their clinical experience in treating subdural fluid collection after mild head trauma. METHODS: Twenty patients with subdural fluid collection after mild head trauma were included in this study. Ventricle size was measured using a modified frontal horn index (mFHI); that is, the largest width of the frontal horns divided by the bicortical distance in the same plane, instead of the inner table distance. Bur hole trephination was performed on the appearance of a subdural fluid collection thicker than 15 mm on computed tomography (CT), persistent (longer than 4 weeks) or increasing in size, and accompanied by neurological symptoms (confusion or memory impairment). During the procedure, subdural pressure was measured using a manometer before opening the dura mater. Subdural pressure varied among the patients, ranging from 3 to 27.5 cm H2O. Four patients with a subdural pressure greater than 15 cm H2O had hydrocephalus after surgery (p < 0.05). Hydrocephalus developed in a pediatric patient (2 years old) with a subdural pressure of 12 cm H2O. All of the patients in whom hydrocephalus developed after bur hole trephination had had enlarged ventricles (mFHI > 33%) on preoperative CT scans. CONCLUSIONS: Monitoring subdural pressure may be a valuable tool for differentiating subdural hygroma from external hydrocephalus in patients with mild head trauma. Additionally, the mFHI reflects the nature of the subdural collection more accurately than the standard frontal horn index.

Adolescent↗

PubMed2006

Combination celecoxib and temozolomide in C6 rat glioma orthotopic model.

The purpose of this study was to determine whether a combination treatment of temozolomide with celecoxib is effective in the rat orthotopic glioma model. After stereotactic injection of C6/LacZ rat glioma cells into the Sprague Dawley rat brain, the rats were randomly assigned to four treatment groups [group 1, control treatment; group 2, celecoxib (25 mg/kg p.o. everyday) alone; group 3, temozolomide (7.5 mg/kg i.p. for 5 days at 2nd week) alone; group 4, a combination of celecoxib and temozolomide]. Rats were sacrificed 18 days after treatment, and the body weight, tumor volume, tumor cell proliferation, microvessel densities, and apoptosis were evaluated. There was a significant reduction of tumor volume in combination group compared to control or single-agent therapy. The median tumor volume was estimated to be 111.5 mm(3) (control), 65.0 mm(3) (celecoxib), 71.8 mm(3) (temozolomide) and 18.7 mm(3) (combination). In the combination group, there was increased tumor cell apoptosis as well as decreased microvessel density and tumor cell proliferation relative to the control and single-agent therapy (P<0.05). Collectively, the data suggest that the combination celecoxib and temozolomide may provide a novel and effective approach to the treatment of glioblastoma.

Animals↗

PubMed2005

Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein.

Numerous studies have suggested that the NF2 protein merlin is involved in the regulation of abnormal cell growth and proliferation. In this study, to better understand the merlin's mechanisms that contribute to the inhibition of tumorigenesis, we examined the potential action of merlin on the cell proliferative signaling pathways in response to growth hormone (GH). Merlin effectively attenuated the GH-induced serum response element (SRE) and Elk-1-mediated transcriptional activation, as well as the endogenous SRE-regulated gene c-fos expression in NIH3T3 cells. In addition, merlin prevented the Raf-1 complex activation process, which resulted in the suppression of MAP kinase/ERK, extracellular signal-regulated kinase (ERKs), and Elk-1 phosphorylation, which are the downstream signals of Raf-1. Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression. These results suggest that merlin contributes, via its protein-to-protein interaction with Grb2 and consequent inhibition of the MAPK pathways, to the regulation of the abnormal cell proliferation, and this provides a further mechanism underlying the tumor suppressor function of merlin.

Animals↗

PubMed2005

Cytotoxicity of rat marrow stromal cells against malignant glioma cells.

OBJECTS: Marrow stromal cells (MSCs) have been shown to have the capacity of orthodox and unorthodox plasticity. In this study, the authors tried to access in vitro cytotoxicity of MSCs from rat and also to differentiate MSCs into immune effector cell. METHODS: Rat MSCs (rMSCs) were isolated by standard methodology and were activated by interleukin-2 (IL-2), interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor, and combinations, which were effector cells. Cytotoxicity of rMSCs and activated rMSCs against the target cells (9L rat glioma cell line) was estimated using visual survival cell assay. Phenotypes of these various activated cells were determined using flow cytometry. The secreted protein from effector cells was estimated by enzyme-linked immunosorbent assay. The expression of immune response-related genes in activated cells was measured. RESULTS: There was a significant cytotoxicity of rMSCs activated with various cytokine combinations. After various cytokine activations of rMSCs, the population of immune effector cells (CD8, CD161a) and immune reaction-related proteins (IL-4, gamma-INF) might increase. Apoptosis may be one of the lysis mechanisms of target cells by activated rMSCs. The contributing genes could be gamma-INF, FasL, and perforin. CONCLUSION: This study suggests that rMSC may be used as adoptive transfer therapy in patients suffering from malignant brain tumor, but we have to investigate orthotopic animal study for the proper translation.

Animals↗

PubMed2005

Clinical and radiological prognostic factors of anaplastic oligodendroglioma treated by combined therapy.

The clinical and radiological prognostic factors were investigated in 32 patients with newly diagnosed anaplastic oligodendroglioma treated by combined therapy using surgery, postoperative radiation therapy, and adjuvant chemotherapy between September 1994 and December 2002. Surgery aimed at total removal was followed by radiotherapy, and 3 weeks later by adjuvant chemotherapy repeated at 6- to 7-week intervals. Survival analysis showed that younger age, absence of preoperative headache, good postoperative Karnofsky Performance Status (KPS) score (>or=80), and relatively small tumor volume (<50 cm3) were predictors for longer survival in univariate analysis (p<0.05). Age and good postoperative KPS score were independent prognostic factors in multivariate analysis (p<0.05). Median survival was 58 months after diagnosis, and the 5-year survival rate was 49%.

Adult↗

PubMed2004

Lymphokine activated killer cells from umbilical cord blood show higher antitumor effect against anaplastic astrocytoma cell line (U87) and medulloblastoma cell line (TE671) than lymphokine activated killer cells from peripheral blood.

OBJECTS: The aims of this study were to assess the cytotoxic capability of lymphokine-activated killer (LAK) cells from umbilical cord blood (UCB), to compare them with those of peripheral blood (PB)-derived cells against anaplastic astrocytoma cell line (U87) and medulloblastoma cell line (TE671), and to identify which mechanism and genes were involved in cytotoxicity. METHODS: The effector cells were generated by interleukin-2 from UCB and PB. The antitumor property of effector cells against the target cells (U87, TE671) were estimated using a visual survival cell assay. The mixed target and effector (UCB) cells were analyzed for whether DNA fragmentation was present or not. Reverse transcription polymerase chain reaction analysis was then performed to estimate the statement of the perforin and FasL genes in activated and inactivated cells from UCB. RESULTS: The higher in vitro antitumor properties of the LAK cells from UCB were observed in comparison to the LAK cells from PB against the U87 and the TE671 ( p<0.05). Apoptosis may be one of the lysis mechanisms of target cells by the LAK cells from UCB. The contributing genes could be FasL and perforin. CONCLUSIONS: This study suggests that UCB may be used as a source of LAK cells in adults and children suffering from anaplastic astrocytoma or medulloblastoma.

Adult↗