Publications by authors named "Seok Gu Kang"

We used deep learning methods to develop an AI model capable of autonomously delineating cancerous regions in digital pathology images (H&E-stained images). By using a transgenic brain tumor model derived from the TS13-64 brain tumor cell line, we digitized a total of 187 H&E-stained images and annotated the cancerous regions in these images to compile a dataset. A deep learning approach was executed through DEEP:PHI, which abstracts Python coding complexities, thereby simplifying the execution of AI training protocols for users.

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Background: Despite available treatment approaches, including surgical resection along with chemotherapy and radiotherapy, glioblastoma (GBM), the most prevalent primary brain tumor, remains associated with a grim prognosis. Although radiotherapy is central to GBM treatment, its combination with bioenergetics regulators has not been validated in clinical practice. Here, we hypothesized that bioenergetics regulators can enhance the radio-sensitivity of GBM tumorspheres (TSs).

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Purpose: To identify a specific subgroup of patients among elderly glioblastoma patients aged 70 years or older with unmethylated MGMT promoters (eGBM-unmethylated) who would significantly benefit from the addition of temozolomide (TMZ) to radiotherapy (RT).

Materials And Methods: Newly diagnosed patients with IDH wild-type eGBM-unmethylated treated with RT were included in this multicenter analysis (n=182). RT dose was 45 Gy in 15 fractions (62.

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Background: Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs).

Methods: The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis.

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Purpose: Severe lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram.

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Article Synopsis
  • Current glioblastoma (GBM) research lacks standardized in vitro cell culture models, mainly using traditional 2D methods, but glioblastoma tumorspheres (TSs) show promise as a model for drug testing and understanding GBM features.* -
  • The study isolated GBM TSs and extracellular matrices from newly diagnosed patients and tested them on five different culture platforms, finding that the liquid media (LM) method matched the transcriptional characteristics of the original tumors most closely.* -
  • The LM platform is easier and more cost-effective for culturing GBM TSs, retaining tumor characteristics, and has potential for further applications in drug screening and personalized medicine.*
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Purpose: Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN).

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  • Reactive astrogliosis, a response to brain pathologies, is influenced by metabolites, particularly acetate from glioblastoma cells, highlighting its role in the surrounding microenvironment.
  • The study utilized in vitro, mouse, and human tissue experiments to link elevated 11C-acetate uptake to reactive astrogliosis, indicating that glioblastoma cell metabolism significantly impacts neighboring astrocytes.
  • Findings suggest that higher volumes of 11C-acetate uptake correlate with worse prognoses, emphasizing 11C-acetate PET’s potential as a diagnostic tool for assessing reactive astrogliosis in glioblastoma patients.
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Purpose: 11 C-acetate (ACE) PET/CT visualizes reactive astrogliosis in tumor microenvironment. This study compared 11 C-ACE and 11 C-methionine (MET) PET/CT for glioma classification and predicting patient survival.

Patients And Methods: In this prospective study, a total of 142 patients with cerebral gliomas underwent preoperative MRI, 11 C-MET PET/CT, and 11 C-ACE PET/CT.

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Background: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM.

Methods: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases.

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Purpose: To develop and validate a dynamic contrast-enhanced (DCE) MRI-based radiomics model to predict epidermal growth factor receptor (EGFR) amplification in patients with glioblastoma, isocitrate dehydrogenase (IDH) wildtype.

Methods: Patients with pathologically confirmed glioblastoma, IDH wildtype, from January 2015 to December 2020, with an EGFR amplification status, were included. Patients who did not undergo DCE or conventional brain MRI were excluded.

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Objectives: Extent of resection (EOR) of contrast-enhancing (CE) and non-enhancing (NE) tumors may have different impacts on survival according to types of adult-type diffuse gliomas in the molecular era. This study aimed to evaluate the impact of EOR of CE and NE tumors in glioma according to the 2021 World Health Organization classification.

Methods: This retrospective study included 1193 adult-type diffuse glioma patients diagnosed between 2001 and 2021 (183 oligodendroglioma, 211 isocitrate dehydrogenase [IDH]-mutant astrocytoma, and 799 IDH-wildtype glioblastoma patients) from a single institution.

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Article Synopsis
  • Identified transcription factors (TFs) that control invasion-related genes in glioblastoma (GBM), highlighting their role in tumor invasiveness.
  • Conducted experiments using 3D invasion assays and transcriptome analyses to assess TF activities, confirming the findings with proteome imaging and mouse models.
  • Discovered that PCBP1 is linked to low invasion, while STAT3 and SRF are associated with high invasion; targeting these TFs could improve treatment outcomes and potentially enhance survival for GBM patients.
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Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period.

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Article Synopsis
  • The Korean Society for Neuro-Oncology (KSNO) developed treatment guidelines for brain tumor patients during the COVID-19 pandemic to address medical resource limitations and ensure proper care during crises.* -
  • A group of 22 neuro-oncology experts used the Delphi method to reach a consensus on recommendations, prioritizing surgeries and therapies based on the urgency of patient needs during a crisis.* -
  • The guidelines emphasize maintaining adequate care for brain tumor patients and suggest utilizing telemedicine as a vital management tool in future health crises.*
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Background: There has been no known serum biomarker to predict the prognosis of atypical meningioma.

Objective: To investigate the prognostic impact of serum biomarkers in patients newly diagnosed with resected intracranial atypical meningiomas.

Methods: This study enrolled 523 patients with atypical meningioma who underwent surgical resection between 1998 and 2018 from 5 Asian institutions.

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Purpose: To comprehensively investigate prognostic factors, including clinical and molecular factors and treatment modalities, in adult glioma patients with leptomeningeal metastases (LM).

Methods: Total 226 patients with LM (from 2001 to 2021 among 1495 grade 2 to 4 glioma patients, 88.5% of LM patients being IDH-wildtype) with complete information on IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status were enrolled.

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Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM patient-derived cells.

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Phenotypic heterogeneity of glioblastomas is a leading determinant of therapeutic resistance and treatment failure. However, functional assessment of the heterogeneity of glioblastomas is lacking. We developed a self-assembly-based assessment system that predicts inter/intracellular heterogeneity and phenotype associations, such as cell proliferation, invasiveness, drug responses, and gene expression profiles.

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Article Synopsis
  • Limited treatment options for glioblastoma (GBM) highlight the potential for targeting cancer-specific metabolic pathways by inhibiting key enzymes CPT1A and G6PD, which are vital for fatty acid oxidation and the pentose phosphate pathway.
  • Experiments demonstrated that knocking down CPT1A and G6PD reduced GBM tumor cell viability and growth, supported by transcriptome analysis and metabolite profiling indicating disrupted metabolic pathways.
  • The combination therapy using etomoxir and DHEA not only inhibited tumor growth in cell cultures but also extended survival in mice models, suggesting a promising therapeutic strategy for GBM.
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Gliomas are the most common primary tumors in the brain and spinal cord. In previous GWASs, SNPs in epidermal growth factor receptor (EGFR) have been reported as risk loci for gliomas. However, EGFR variants associated with gliomas in the Korean population remain unstudied.

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Article Synopsis
  • The study found that leptomeningeal metastases (LMs) occur more frequently in glioma patients than previously thought, with an incidence of 16.2% identified through advanced postcontrast FLAIR imaging.
  • Key molecular predictors for LMs include IDH-wildtype status and unmethylated MGMT promoter, along with clinical factors like WHO grade 4 and nonlobar tumor location at diagnosis.
  • Patients with LMs experienced significantly worse overall survival compared to those without, highlighting the need for better diagnostic methods and the influence of molecular markers on patient outcomes.
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Introduction: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM.

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Purpose: Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model.

Methods: PDT was performed using a 635 nm light-emitting diode (LED).

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