Background: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. Methods: The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). Results: The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. Conclusion This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

Sociability is the disposition to interact with one another. Rodents have a rich repertoire of social behaviors and demonstrate strong sociability. Various methods have been established to measure the sociability of rodents in simple and direct ways, which includes reciprocal social interaction, juvenile social play, and three-chamber social tests. There are possible confounding factors while performing some of these tasks, such as aggression, avoidance of interaction by the stimulus mouse, exposure to a new environment, and lengthy procedures. The present study devised a method to complement these shortcomings and measure sociability as a group in the home cage setting, which prevents group-housed mice from isolation or exposure to a new environment. The home cage social test can allow high-throughput screening of social behaviors in a short amount of time. We developed two types of home cage setup: a home cage social target interaction test that measures sociability by putting the wire cage in the center area of the cage and a home cage two-choice sociability and social preference test that measures both sociability or social preference by putting cage racks at opposite sides of the cage. Interestingly, our results showed that the two types of home cage setup that we used in this study can extract abnormal social behaviors in various animal models, similar to the three-chamber assay. Thus, this study establishes a new and effective method to measure sociability or social preference that could be a complementary assay to evaluate the social behavior of mice in various setup conditions.
Aggression ; Animals ; Complement System Proteins ; Interpersonal Relations ; Mass Screening ; Methods ; Mice ; Models, Animal ; Rodentia ; Social Behavior

Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.
Adult ; Animals ; Autistic Disorder ; Blood-Brain Barrier ; Cell Death ; Cerebrospinal Fluid ; Grooming ; Humans ; Injections, Intraperitoneal ; Mass Screening ; Mice ; Mice, Inbred ICR ; N-Methylaspartate ; Neurons ; Nociception ; Pathology ; Synaptic Transmission ; Tail

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence-associated β-galactosidase (SA-β-gal) activity. Tenovin-1-treated astrocytes showed increased SA-β-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-1β, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.
Aging ; Animals ; Astrocytes ; Blood-Brain Barrier ; Brain ; Cell Aging ; Cell Count ; Cell Cycle Checkpoints ; Interleukin-6 ; Language ; Memory ; Neurodegenerative Diseases ; Neurons ; Permeability ; Phenotype ; Rats ; Wound Healing

Brain aging is an inevitable process characterized by structural and functional changes and is a major risk factor for neurodegenerative diseases. Most brain aging studies are focused on neurons and less on astrocytes which are the most abundant cells in the brain known to be in charge of various functions including the maintenance of brain physical formation, ion homeostasis, and secretion of various extracellular matrix proteins. Altered mitochondrial dynamics, defective mitophagy or mitochondrial damages are causative factors of mitochondrial dysfunction, which is linked to age-related disorders. Etoposide is an anti-cancer reagent which can induce DNA stress and cellular senescence of cancer cell lines. In this study, we investigated whether etoposide induces senescence and functional alterations in cultured rat astrocytes. Senescence-associated β-galactosidase (SA-β-gal) activity was used as a cellular senescence marker. The results indicated that etoposide-treated astrocytes showed cellular senescence phenotypes including increased SA-β-gal-positive cells number, increased nuclear size and increased senescence-associated secretory phenotypes (SASP) such as IL-6. We also observed a decreased expression of cell cycle markers, including Phospho-Histone H3/Histone H3 and CDK2, and dysregulation of cellular functions based on wound-healing, neuronal protection, and phagocytosis assays. Finally, mitochondrial dysfunction was noted through the determination of mitochondrial membrane potential using tetramethylrhodamine methyl ester (TMRM) and the measurement of mitochondrial oxygen consumption rate (OCR). These data suggest that etoposide can induce cellular senescence and mitochondrial dysfunction in astrocytes which may have implications in brain aging and neurodegenerative conditions.
Aging ; Animals ; Astrocytes ; Brain ; Cell Aging ; Cell Cycle ; Cell Line ; DNA ; Etoposide ; Extracellular Matrix Proteins ; Homeostasis ; Interleukin-6 ; Membrane Potential, Mitochondrial ; Mitochondria ; Mitochondrial Degradation ; Mitochondrial Dynamics ; Neurodegenerative Diseases ; Neurons ; Neuroprotection ; Oxygen Consumption ; Phagocytosis ; Phenotype ; Rats ; Risk Factors ; Wound Healing

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hypo-osmotic hyponatremia. There are several etiologies of SIADH including neuroendocrine tumor, pulmonary disease, infection, trauma, and medications. Here, we report a case of SIADH associated with a schwannoma involving the mediastinum in a 75-year-old woman who presented with nausea, vomiting, and general weakness. Laboratory testing showed hypo-osmolar hyponatremia, with a serum sodium level of 102mmol/L, serum osmolality of 221mOsm/kg, urine osmolality of 382mOsm/kg, urine sodium of 55 mmol/L, and plasma antidiuretic hormone (ADH) of 4.40 pg/mL. Chest computed tomography identified a 1.5-cm-sized solid enhancing nodule in the right lower paratracheal area. A biopsy specimen was obtained by video-assisted thoracoscopic surgery, which was diagnosed on pathology as a schwannoma. The hyponatremia was completely resolved after schwannoma resection and plasma ADH level decreased from 4.40 pg/mL to 0.86 pg/mL. This case highlights the importance of suspecting and identifying the underlying cause of SIADH when faced with refractory or recurrent hyponatremia, and that on possibility is mediastinal schwannoma
Aged ; Biopsy ; Female ; Humans ; Hyponatremia ; Inappropriate ADH Syndrome ; Lung Diseases ; Mediastinum ; Nausea ; Neurilemmoma* ; Neuroendocrine Tumors ; Osmolar Concentration ; Pathology ; Plasma ; Sodium ; Thoracic Surgery, Video-Assisted ; Thorax ; Vomiting

BACKGROUND/AIMS: During endoscopic retrograde cholangiopancreatography (ERCP), all efforts should be made to be aware of radiation hazards and to reduce radiation exposure. The aim of this study was to investigate the status of radiation protective equipment and the awareness of radiation exposure in health care providers performing ERCP in Korean hospitals. METHODS: A survey with a total of 42 questions was sent to each respondent via mail or e-mail between October 2010 and March 2011. The survey targeted nurses and radiation technicians who participated in ERCP in secondary or tertiary referral centers. RESULTS: A total of 78 providers from 38 hospitals responded to the surveys (response rate, 52%). The preparation and actual utilization rates of protective equipment were 55.3% and 61.9% for lead shields, 100% and 98.7% for lead aprons, 47.4% and 37.8% for lead glasses, 97.4% and 94.7% for thyroid shields, and 57.7% and 68.9% for radiation dosimeters, respectively. The common reason for not wearing protective equipment was that the equipment was bothersome, according to 45.7% of the respondents. CONCLUSIONS: More protective equipment, such as lead shields and lead glasses, should be provided to health care providers involved in ERCP. In particular, the actual utilization rate for lead glasses was very low.
Cholangiopancreatography, Endoscopic Retrograde ; Data Collection ; Delivery of Health Care ; Electronic Mail ; Eyeglasses ; Glass ; Health Personnel ; Humans ; Korea ; Postal Service ; Referral and Consultation ; Thyroid Gland

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma.
Antimetabolites, Antineoplastic/therapeutic use ; Azacitidine/analogs & derivatives/therapeutic use ; Carcinoma, Hepatocellular/drug therapy/*genetics ; Cell Line, Tumor ; CpG Islands ; *DNA Methylation ; GPI-Linked Proteins/genetics ; Gene Expression Profiling ; Homeodomain Proteins/genetics ; Humans ; Interferon Regulatory Factors/genetics ; Liver Neoplasms/drug therapy/*genetics ; Neuropeptide Y/genetics ; Oligonucleotide Array Sequence Analysis ; Promoter Regions, Genetic ; Tumor Necrosis Factor Decoy Receptors/genetics

BACKGROUND: The incidence of atherosclerosis is well correlated with the progression of type 2 diabetes mellitus. High plasma glucose in uncontrolled diabetic patients evokes many vascular complications such as atherosclerosis. Specifically, high glucose was reported to induce thrombospondin-1 (TSP-1), which activates matrix metalloproteinase-2 (MMP-2) and leads to the invasion of vascular smooth muscle cells (VSMCs) into the intima. Catechins with antioxidant effects are known to inhibit MMP-2 activity. Therefore, this study was aimed at revealing the effect of epicatechin, one of catechins, on high glucose-induced TSP-1 and the invasiveness of VSMCs. METHODS: VSMCs were primarily isolated from Sprague-Dawley rat aorta. The VSMCs were incubated with different doses (30, 100 and 300 micrometer) of epicatechin under high glucose concentration (30 mM). The TSP-1 protein and mRNA expressions were analyzed by performing Western blotting and Northern blot analyses, respectively. RT-PCR was performed to observe the MMP-2 mRNA expression. Gelatin zymography was performed for the measurement of MMP-2 activity. Invasion assays were performed to evaluate the invasiveness of VSMCs. RESULTS: Epicatechin inhibited the high glucose-induced TSP-1 expression and the MMP-2 activity in a dose-dependent manner. Also, epicatechin inhibited the high glucose-induced invasiveness of VSMCs across the matrix barrier in a dose-dependent fashion. CONCLUSION: Collectively, epicatechin may prevent the high glucose-induced proliferation and invasion of VSMCs by inhibiting the TSP-1 expression and the MMP-2 activity. Therefore, epicatechin appears to play a protective role in the development of atherosclerosis.
Animals ; Antioxidants ; Aorta ; Atherosclerosis ; Blood Glucose ; Blotting, Northern ; Blotting, Western ; Catechin* ; Diabetes Mellitus, Type 2 ; Gelatin ; Glucose ; Humans ; Incidence ; Matrix Metalloproteinase 2 ; Muscle, Smooth, Vascular* ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Thrombospondin 1*

BACKGROUND: The incidence of atherosclerosis is well correlated with the progression of type 2 diabetes mellitus. High plasma glucose in uncontrolled diabetic patients evokes many vascular complications such as atherosclerosis. Specifically, high glucose was reported to induce thrombospondin-1 (TSP-1), which activates matrix metalloproteinase-2 (MMP-2) and leads to the invasion of vascular smooth muscle cells (VSMCs) into the intima. Catechins with antioxidant effects are known to inhibit MMP-2 activity. Therefore, this study was aimed at revealing the effect of epicatechin, one of catechins, on high glucose-induced TSP-1 and the invasiveness of VSMCs. METHODS: VSMCs were primarily isolated from Sprague-Dawley rat aorta. The VSMCs were incubated with different doses (30, 100 and 300 micrometer) of epicatechin under high glucose concentration (30 mM). The TSP-1 protein and mRNA expressions were analyzed by performing Western blotting and Northern blot analyses, respectively. RT-PCR was performed to observe the MMP-2 mRNA expression. Gelatin zymography was performed for the measurement of MMP-2 activity. Invasion assays were performed to evaluate the invasiveness of VSMCs. RESULTS: Epicatechin inhibited the high glucose-induced TSP-1 expression and the MMP-2 activity in a dose-dependent manner. Also, epicatechin inhibited the high glucose-induced invasiveness of VSMCs across the matrix barrier in a dose-dependent fashion. CONCLUSION: Collectively, epicatechin may prevent the high glucose-induced proliferation and invasion of VSMCs by inhibiting the TSP-1 expression and the MMP-2 activity. Therefore, epicatechin appears to play a protective role in the development of atherosclerosis.
Animals ; Antioxidants ; Aorta ; Atherosclerosis ; Blood Glucose ; Blotting, Northern ; Blotting, Western ; Catechin* ; Diabetes Mellitus, Type 2 ; Gelatin ; Glucose ; Humans ; Incidence ; Matrix Metalloproteinase 2 ; Muscle, Smooth, Vascular* ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger ; Thrombospondin 1*