BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Brain ; Central Nervous System ; Chemoradiotherapy ; Diagnosis ; Drug Therapy ; Glioblastoma ; Humans ; Korea ; Radiotherapy

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult ; Astrocytoma ; Brain ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Follow-Up Studies ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Oligodendroglioma ; Radiotherapy ; World Health Organization

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult ; Astrocytoma ; Brain ; Brain Neoplasms ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Lomustine ; Oligodendroglioma ; Radiotherapy ; World Health Organization

A myxoma is a benign tumor found in the heart and in various soft tissues; however, a corneal myxoma is rare. A mucinous mass of unknown etiology was observed on the left cornea of a 32-year-old male patient. We performed deep anterior lamellar keratoplasty using acellular corneal tissue and concurrent amniotic membrane transplantation. Hematoxylin and eosin staining revealed vacuolation of the parenchyma and myxoid change in the corneal tissue that occurred in the anterior half of the corneal parenchyma. We identified a myxoid stroma by Alcian blue staining and observed collagen fibers with denatured stroma by Masson trichrome staining. The patient's visual acuity improved from light perception to 20 / 200, and the intraocular pressure remained within the normal range for one year after surgery. The transplanted cornea survived successfully with well-maintained transparency, and recurrence was not observed one year after surgery.
Adult ; *Cornea ; Corneal Stroma/cytology/*transplantation ; Corneal Transplantation/*methods ; Eye Neoplasms/diagnosis/*surgery ; Humans ; Male ; Myxoma/diagnosis/*surgery

A myxoma is a benign tumor found in the heart and in various soft tissues; however, a corneal myxoma is rare. A mucinous mass of unknown etiology was observed on the left cornea of a 32-year-old male patient. We performed deep anterior lamellar keratoplasty using acellular corneal tissue and concurrent amniotic membrane transplantation. Hematoxylin and eosin staining revealed vacuolation of the parenchyma and myxoid change in the corneal tissue that occurred in the anterior half of the corneal parenchyma. We identified a myxoid stroma by Alcian blue staining and observed collagen fibers with denatured stroma by Masson trichrome staining. The patient's visual acuity improved from light perception to 20 / 200, and the intraocular pressure remained within the normal range for one year after surgery. The transplanted cornea survived successfully with well-maintained transparency, and recurrence was not observed one year after surgery.
Adult ; *Cornea ; Corneal Stroma/cytology/*transplantation ; Corneal Transplantation/*methods ; Eye Neoplasms/diagnosis/*surgery ; Humans ; Male ; Myxoma/diagnosis/*surgery

PURPOSE: Small size of recombinant scFv antibody has many advantages such as rapid blood clearances and improved targeting antibodies to tumor region. On the other hand owing to small size, number of amino group is insufficient in conjugation with chelator and fluorescence labeling. This study is to introduce poly lysine tag to the C-terminal end of scFv lym-1 sequence for fluorescence chelator conjugation. MATERIALS AND METHODS: Poly lysine scFv lym-1 gene, cloned into pET-22b (+) vector, was expressed in E. coli BL21 (DE3) strain. Antibody purification was performed with Ni-NTA column and then size exclusion column chromatography. Expression and purification levels of poly lysine tagged scFv lym-1 antibody were confirmed by western blot analysis. I-124, I-125, I-131 and Tc-99m were used for radiolabeling of purified poly lysine scFv lym-1. Flow cytometry analysis of FITC conjugated poly lysine scFv lym-1 was performed for confirmation of immunoreactivity of human Burkitt`s lymphoma cells. RESULTS: Poly lysine scFv lym-1 antibody was purified through two steps and identified as molecular weight of 48 KDa. Radiolabeling yields of I-124, I-125, I-131 and Tc-99m into poly lysine scFv lym-1 were >99%, >99%, >95% and >99%, respectively. Flow cytometry analysis of poly lysine scFv and scFv lym-1 was showed similar immunoreactivity to human Burkitt`s lymphoma cells. CONCLUSION: Poly lysine tag was useful for the sufficient number of amino groups to scFv lym-1 antibody for chelator conjugation with minimizing loss of immunoreactivity.
Antibodies ; Blotting, Western ; Chromatography ; Clone Cells ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; Fluorescence ; Hand ; Humans ; Lymphoma ; Lysine ; Molecular Weight ; Sprains and Strains

PURPOSE: Hydrodynamic-based procedure is a simple and effective gene delivery method to lead a high gene expression in liver tissue. Non-invasive imaging reporter gene system has been used widely with herpes simplex virus type 1 thymidine kinase (HSV1-tk) and its various substrates. In the present study, we investigated to image the expression of HSV1-tk gene with 5-(2-iodovinyl)-2'-deoxyuridine (IVDU) in mouse liver by the hydrodynamicbased procedure. MATERIALS AND METHODS: HSV1-tk or enhanced green fluorescence protein (EGFP) encoded plasmid DNA was transferred into the mouse liver by hydrodynaminc injection. At 24 h post-injection, RT-PCR, biodistribution, fluorescence imaging, nuclear imaging and digital wholebody autoradiography (DWBA) were performed to confirm transferred gene expression. RESULTS: In RT-PCR assay using mRNA from the mouse liver, specific bands of HSV1-tk and EGFP gene were observed in HSV1-tk and EGFP expressing plasmid injected mouse, respectively. Higher uptake of radiolabeled IVDU was exhibited in liver of HSV1-tk gene transferred mouse by biodistribution study. In fluorescence imaging, the liver showed specific fluorescence signal in EGFP gene transferred mouse. Gamma-camera image and DWBA results showed that radiolabeled IVDU was accumulated in the liver of HSV1-tk gene transferred mouse. CONCLUSION: In this study, hydrodynamic-based procedure was effective in liver-specific gene delivery and it could be quantified with molecular imaging methods. Therefore, co-expression of HSV1-tk reporter gene and target gene by hydrodynamic-based procedure is expected to be a useful method for the evaluation of the target gene expression level with radiolabeled IVDU.
Animals ; Autoradiography ; DNA ; Fluorescence ; Gene Expression ; Genes, Reporter ; Herpes Simplex ; Herpesvirus 1, Human ; Idoxuridine ; Liver ; Methylmethacrylates ; Mice ; Molecular Imaging ; Optical Imaging ; Plasmids ; Polystyrenes ; RNA, Messenger ; Simplexvirus ; Thymidine Kinase

PURPOSE: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [18F]FDG small animal PET and clinical CT. MATERIALS AND METHODS: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 degrees C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [18F]FDG and compared pattern of [18F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [18F]FDG image was obtained and fused with anatomical clinical CT image. RESULTS: Average blood glucose concentration in normal mice were 128.0+/-23.87 and 86.0+/-21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6+/-0.48 and 12.1+/-0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [18F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [18F]FDG small animal PET image was confirmed by fusion image using clinical CT. CONCLUSION: Tumor imaging in small animal lung region with [18F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [18F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.
Anesthesia ; Animals ; Animals* ; Blood Glucose ; Fasting ; Glucose ; Injections, Intravenous ; Isoflurane ; Lung* ; Melanoma ; Mice* ; Neoplasm Metastasis*

PURPOSE: Recombinant ScFv lym-1 was produced, using pET vector system for large scale production. METHODS: ScFv lym-1 gene inserted pET-22b (+) vector, was expressed in E.coli BL-21 strain. ScFv lym-1 antibody extracted from periplasm, was purified with His-Taq column. To evaluated immunoreactivity with Raji cell, ScFv lym-1 was labeled with I-125 and I-125 ScFv lym-1 was purified with desalting column. Raji cell was injected into the C57BR/cdJ SCID mice. Gamma camera imaging were taken time point at 1, 8, 24, and 48 hr with 8 mm pinhole collimator. RESULTS: An active scFv lym-1 could be produced in E.coli with soluble from using pET vector system. Immunoreactivity and affinity constant of IgG lym-1 were 54% and 1.83 x 10(9) M(-1), respectively, and those of scFv lym-1 were 53.7% and 1.46 x 10(9) M(-1), respectively. Biodistribution of I-125 scFv lym-1 antibody showed faster clearance in blood, spleen, kidney and than I-125 IgG lym-1 antibody. Gamma camera image of I-125 scFv lym-1 antibody showed faster clearance and tumor targeting liver than I-125 IgG lym-1 antibody. CONCLUSIONS: In vitro properties of scFv lym-1 were similar to those of IgG lym-1. ScFv lym-1 showed faster blood clearance than IgG lym-1. These results suggest that scFv lym-1 antibody can be useful for tumor imaging agent.
Animals ; Gamma Cameras ; Immunoglobulin G ; Kidney ; Liver ; Lymphoma* ; Mice ; Mice, SCID ; Periplasm ; Radionuclide Imaging ; Spleen

PURPOSE: Ethylenediamine-tetramethylenephosphonic acid (EDTMP) has widely used chelator for the labeling of bone seeking radiopharmaceuticals complexed with radiometals. 153Sm can be produced by the HANARO reactor at the Korea Atomic Energy Research Institute, Taejon, Korea. 153Sm has favourable radiation characteristics T1/2=46.7 h, beta max=0.81 MeV (20%), 0.71 MeV (49%), 0.64 MeV (30%) and gamma=103 keV (30%) emission which is suitable for imaging purposes during therapy. We investigated the labeling condition of 153Sm-EDTMP and imaging of 153Sm-EDTMP in normal rats. MATERIALS AND METHODS: EDTMP 20 mg was solved in 0.1 mL 2 M NaOH. 153SmCl3 was added to EDTMP solution and pH of the reaction mixtures was adjusted to 8 and 12, respectively. Radiochemical purity was determined with paper chromatography. After 30 min. reaction, reaction mixtures were neutralized to pH 7.4, and the stability was estimated upto 120 hrs. Imaging studies of each reaction were perfomed in normal rats (37 MBq/0.1 mL). RESULTS: The labeling yield of 153Sm-EDTMP was 99%. The stability of pH 8 reaction at 60, 96 and 120 hr was 99%, 95%, 89% and that of pH 12 at 36, 60, 96 and 120 hr was 99%, 95%, 88%, 66%, respectively. The 153Sm-EDTMP showed constantly higher bone uptake from 2 to 48 hr after injection. CONCLUSION: 153Sm-EDTMP, labeled at pH 8 reaction condition, has been stably maintained. Image of 153Sm-EDTMP at 2, 24, 48 hr after injection, demonstrate that 153Sm-EDTMP is a good bone seeking radiopharmaceuticals.
Academies and Institutes ; Animals* ; Chromatography, Paper ; Daejeon ; Hydrogen-Ion Concentration ; Korea ; Nuclear Energy ; Radiopharmaceuticals ; Rats