Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

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

PURPOSE: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. MATERIALS AND METHODS: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. RESULTS: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). CONCLUSIONS: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.
Ascites ; Biomarkers ; Carcinoembryonic Antigen ; Carcinoma ; Cohort Studies ; Diagnosis ; Down-Regulation ; Exosomes ; Humans ; Liver ; MicroRNAs ; Prognosis ; RNA ; Stomach Neoplasms

BACKGROUND: Accurate volume measurement is important in the management of patients with congestive heart failure or renal insufficiency. A bioimpedance analyser can estimate total body water in litres and has been widely used in clinical practice due to its non-invasiveness and ease of results interpretation. To change impedance data to volumetric data, bioimpedance analysers use equations derived from data from healthy subjects, which may not apply to patients with other conditions. Bioelectrical impedance vector analysis (BIVA) was developed to overcome the dependence on those equations by constructing vector plots using raw impedance data. BIVA requires normal reference plots for the proper interpretation of individual vectors. The aim of this study was to construct normal reference vector plots of bioelectrical impedance for Koreans. METHODS: Bioelectrical impedance measurements were collected from apparently healthy subjects screened according to a comprehensive physical examination and medical history performed by trained physicians. Reference vector contours were plotted on the RXc graph using the probability density function of the bivariate normal distribution. We further compared them with those of other ethnic groups. RESULTS: A total of 242 healthy subjects aged 22 to 83 were recruited (137 men and 105 women) between December 2015 and November 2016. The centers of the tolerance ellipses were 306.3 Ω/m and 34.9 Ω/m for men and 425.6 Ω/m and 39.7 Ω/m for women. The ellipses were wider for women than for men. The confidence ellipses for Koreans were located between those for Americans and Spaniards without overlap for both genders. CONCLUSION: This study presented gender-specific normal reference BIVA plots and corresponding tolerance and confidence ellipses on the RXc graph, which is important for the interpretation of BIA-reported volume status in patients with congestive heart failure or renal insufficiency. There were noticeable differences in reference ellipses with regard to gender and ethnic groups.
Adult ; Blood Volume ; Body Fluid Compartments ; Body Water ; Electric Impedance ; Ethnic Groups ; Female ; Healthy Volunteers ; Heart Failure ; Humans ; Male ; Physical Examination ; Renal Insufficiency