ABSTRACT
The Korean Society of Radiology and Medical Guidelines Committee amended the existing 2016 guidelines to publish the “Korean Clinical Practice Guidelines for Adverse Reactions to Iodide Contrast for Injection and Gadolinium Contrast for MRI: The Revised Clinical Consensus and Recommendations (2022 Third Edition).” Expert members recommended and approved by the Korean Society of Radiology, the Korean Academy of Asthma, Allergy and Clinical Immunology, and the Korean Nephrology Society participated together. According to the expert consensus or systematic literature review, the description of the autoinjector and connection line for the infection control while using contrast medium, the acute adverse reaction, and renal toxicity to iodized contrast medium were modified and added. We would like to introduce the revised contents.
ABSTRACT
Lewy bodies (LBs) and Lewy neurites (LNs) are pathological hallmarks of Parkinson’s disease (PD) or dementia with LBs (DLB). Incidental Lewy body disease (iLBD) is defined when LBs and LNs are found in the brain of normal elderly individuals. A 65-year-old man presented with autopsy-proven Lewy body pathology (LBP). He had never complained of cognitive impairments or parkinsonian motor symptoms, and he had always maintained independence in activities of daily living. Hypopigmentations in the locus coeruleus and substantia nigra were discovered during the autopsy. The patient showed severe-to-extremely severe LBs in the neocortex and limbic areas, except in the nucleus basalis of Meynert, amygdala, and brainstem, according to microscopic findings. Hence, using several of the previously known staging systems, it was difficult to classify the patient’s LBP type. Furthermore, these findings were unique because they had never been observed before in iLBD.
ABSTRACT
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Despite biochemically classified as 4R tauopathies, tufted astrocytes of PSP and astrocytic plaque of CBD show pathologically important differences. Herein, we report a 68-year-old man with pathologically confirmed CBD. He was clinically suspected to have PSP because of progressive gait disturbances, frequent falls, and vertical saccade limitation. Neurological examination performed at age 71 revealed symmetrical bradykinesia, axial rigidity, and postural instability with worsening of early existing symptoms. Magnetic resonance imaging of the brain taken at age 70 detected midbrain and left frontotemporal atrophy and right middle cerebral artery infarction. Left frontotemporoparietal hypometabolism and asymmetrically decreased fluoro-propyl-carbomethoxy-iodophenyl-tropane uptake in the basal ganglia were observed. The autopsy was performed at the time of his death (at age 72), which revealed severe pallor of the substantia nigra and mildly hypopigmented locus ceruleus.AT8 immunohistochemistry and Gallyas staining revealed tau-positive neuronal and glial inclusions, astrocytic plaques, ballooned neurons, and numerous threads in both gray and white matter. No abnormal inclusions were revealed by beta-amyloid, α-synuclein and TDP-43 immunohistochemistry. In our case, cerebral infarction, periventricular and deep white matter ischemic changes, and midbrain atrophy were likely to produce PSP–CBD overlapping symptoms. However, our patient was finally confirmed to have CBD based on pathological findings such as astrocytic plaques.
ABSTRACT
Background/Aims@#The effect of peroral endoscopic myotomy (POEM) on esophageal body movement in achalasia is poorly understood. This study aims to evaluate morphological changes in esophageal body movement after POEM in type III achalasia by analyzing intraluminal ultrasound (US) images in comparison to type I and II achalasia. @*Methods@#Intraluminal US images and impedance values of the distal esophagus from 47 achalasia patients who underwent POEM or pneumatic dilatation (PD) (30 patients in the POEM group and 17 patients in the PD group) with pre- and post-procedural high-resolution impedance manometry and intraluminal US examinations were analyzed. The muscle thickness (MT), muscle cross-sectional area, lumen cross-sectional area (LCSA), contractility and distensibility indices, swallow-to-distension interval, and distension duration during each bolus transport were analyzed. @*Results@#The MT increased and LCSA decreased significantly (P < 0.001), but the contractility index was not improved after POEM or PD in type I achalasia. Baseline MT increased and LCSA decreased significantly after POEM and PD in type II achalasia (P < 0.001). In contrast, MT and the swallow-to-distension interval decreased and the distension LCSA/duration and contractility index increased after POEM in type III achalasia (P < 0.001). In contrast to type I and II achalasia, in type III achalasia, these effects were unique to the POEM group. @*Conclusions@#POEM decreased the esophageal LCSA by decreasing intrabolus pressure without improving contractility in type I and II achalasia. In contrast, POEM increased esophageal body distension and contractility and improved the inhibitory process during bolus transport in type III achalasia.
ABSTRACT
Background@#Treatment protocols for light chain (AL) amyloidosis have been derived from myeloma treatment. Bortezomib is a key drug used for the treatment of myeloma and AL amyloidosis. We retrospectively investigated the efficacy and toxicity of bortezomib-based chemotherapy in patients with newly diagnosed AL amyloidosis. @*Methods@#We reviewed the outcomes of newly diagnosed autologous stem cell transplantation (auto-SCT)-ineligible AL amyloidosis patients who received bortezomib-based chemotherapy at a referral center between 2011 and 2017. @*Results@#Of 63 patients who received bortezomib-based chemotherapy, 32 were male, and the median age was 66 years (range, 42‒82 yr). The hematologic overall response rate (ORR) was 65.1%, and the chemotherapy regimen with the best hematologic response was VMP (75.7%, 28/37). Sixty patients had significant organ (heart or kidney) involvement; 28.3% of patients (N=17) had major organ responses after chemotherapy. With a median follow-up of 34 months, there was no significant difference in progression-free survival (P =0.49) or overall survival (P =0.67) according to regimen. Most hematologic and non-hematologic problems were manageable. @*Conclusion@#Various chemotherapy combinations based on bortezomib are currently employed in the clinical setting, but no difference was found in terms of efficacy or toxicity.
ABSTRACT
Background@#To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. @*Methods@#Data on 3,298 women, aged 40–80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. @*Results@#In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. @*Conclusion@#Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.
ABSTRACT
The reproductive tracts have an intimate relationship with reproduction because there are bacterial communities that can affect reproductive health. The differences in the bacterial community of periparturient dairy cows were investigated. Vaginal and fecal samples were collected seven days before and after calving, and DNA was extracted to sequence the V3-V4 regions of the 16S rRNA genes. In the postpartum vaginas, operational taxonomic units, Chao1, Shannon, and Simpson were decreased, and phyla Fusobacteria and Bacteroidetes were increased. In summary, bacterial abundance can affect the periparturient biological differences in dairy cows, suggesting a susceptibility to infection within one week after calving.
ABSTRACT
Background@#Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. @*Objectives@#To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. @*Methods@#Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive ( IDO, PTGS2, and PTGES ), inflammatory (IL6 and IL10 ), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. @*Results@#cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. @*Conclusions@#The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.
ABSTRACT
Background@#To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. @*Methods@#Data on 3,298 women, aged 40–80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. @*Results@#In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. @*Conclusion@#Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.
ABSTRACT
The reproductive tracts have an intimate relationship with reproduction because there are bacterial communities that can affect reproductive health. The differences in the bacterial community of periparturient dairy cows were investigated. Vaginal and fecal samples were collected seven days before and after calving, and DNA was extracted to sequence the V3-V4 regions of the 16S rRNA genes. In the postpartum vaginas, operational taxonomic units, Chao1, Shannon, and Simpson were decreased, and phyla Fusobacteria and Bacteroidetes were increased. In summary, bacterial abundance can affect the periparturient biological differences in dairy cows, suggesting a susceptibility to infection within one week after calving.
ABSTRACT
Background@#Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable. @*Objectives@#To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient in vitro. @*Methods@#Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization. For major DLA genotyping (DQA1, DQB1, and DRB1), peripheral blood mononuclear cells (PBMCs) from two dogs (Dogs 1 and 2) were analyzed by direct sequencing of polymerase chain reaction (PCR) products. The cA-MSCs were co-cultured at a 1:10 ratio with activated PBMCs (DLA matching or mismatching) for 3 days and analyzed for immunosuppressive ( IDO, PTGS2, and PTGES ), inflammatory (IL6 and IL10 ), and apoptotic genes (CASP8, BAX, TP53, and BCL2) by quantitative real-time reverse transcriptase-PCR. @*Results@#cA-MSCs were expressed cell surface markers such as CD90+/44+/29+/45- and differentiated into osteocytes, chondrocytes, and adipocytes in vitro. According to the Immuno Polymorphism Database, DLA genotyping comparisons of Dogs 1 and 2 revealed complete differences in genes DQA1, DQB1, and DRB1. In the co-culturing of cA-MSCs and PBMCs, DLA mismatch between the two cell types induced a significant increase in the expression of immunosuppressive (IDO/PTGS2) and apoptotic (CASP8/BAX) genes. @*Conclusions@#The administration of cA-MSCs matching the recipient DLA type can alleviate the need to regulate excessive immunosuppressive responses associated with genes, such as IDO and PTGES. Furthermore, easy and reliable DLA genotyping technology is required because of the high degree of genetic polymorphisms of DQA1, DQB1, and DRB1 and the low readability of DLA 88.
ABSTRACT
Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.
ABSTRACT
Vasomotor symptoms (VMS), such as hot flashes and night sweating, are classic menopausal symptoms experienced by a majority of perimenopausal and postmenopausal women. VMS have received a great deal of attention due to their relationship with cardiometabolic risk. Further, accumulating evidence indicates that VMS are associated with an increased risk of several chronic diseases, including metabolic syndrome, type 2 diabetes mellitus, nonalcoholic fatty liver diseases, and osteoporosis in perimenopausal and postmenopausal women. These findings suggest VMS as biomarkers of impaired cardiometabolic conditions rather than just temporary symptoms in menopausal women, warranting further studies to confirm the casual relationship of VMS with these diseases and the exact underlying mechanism in this context.
ABSTRACT
Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
ABSTRACT
Over-expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) isoform enzymes was recently reported in various cancers including Burkitt’s lymphoma (BL). However, the functions of Nox isoform enzymes in BL remain poorly understood. In this study, Nox isoform expression and the effects of a Nox-specific inhibitor were evaluated in Epstein-Barr virus (EBV)-positive Raji BL cells in comparison with EBV-negative Ramos BL cells. To evaluate Nox enzyme expression in Raji and Ramos BL cells, polymerase chain reaction (PCR) and western blot analysis were performed. To verify the intracellular signaling mechanism of the Nox inhibitor-induced apoptosis of Raji cells, WST-1 assay, trypan blue exclusion method, flow cytometry, PCR, western blotting, and bromodeoxyuridine staining were conducted. Experiments using the pan-caspase inhibitor z-VAD, reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), and Bim inhibitor 1 were performed. PCR and western blot results showed that Nox isoform enzymes were highly expressed in EBV-positive BL Raji cells compared with EBV-negative BL Ramos cells. The Nox2 inhibitor induced apoptosis of Raji cells in time- and dosedependent manners. The Nox2 inhibitor also caused up-regulation of Bim and Noxa, down-regulation of Mcl-1, translocation of Bax, release of cytochrome c, and caspase cascade activation, resulting in apoptosis. Furthermore, z-VAD, NAC, and BI-1 effectively blocked the Nox2 inhibitor-induced apoptosis of Raji cells. Taken together, these results provide a novel insight into the mechanism of Nox inhibitor-induced apoptosis and evidence for Nox as a therapeutic target to treat EBV-positive malignancies.
ABSTRACT
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
ABSTRACT
Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.
ABSTRACT
Vasomotor symptoms (VMS), such as hot flashes and night sweating, are classic menopausal symptoms experienced by a majority of perimenopausal and postmenopausal women. VMS have received a great deal of attention due to their relationship with cardiometabolic risk. Further, accumulating evidence indicates that VMS are associated with an increased risk of several chronic diseases, including metabolic syndrome, type 2 diabetes mellitus, nonalcoholic fatty liver diseases, and osteoporosis in perimenopausal and postmenopausal women. These findings suggest VMS as biomarkers of impaired cardiometabolic conditions rather than just temporary symptoms in menopausal women, warranting further studies to confirm the casual relationship of VMS with these diseases and the exact underlying mechanism in this context.
ABSTRACT
Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment.Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39+ cells among CD8+T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39+ CD8+ T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
ABSTRACT
Over-expression of nicotinamide adenine dinucleotide phosphate oxidase (Nox) isoform enzymes was recently reported in various cancers including Burkitt’s lymphoma (BL). However, the functions of Nox isoform enzymes in BL remain poorly understood. In this study, Nox isoform expression and the effects of a Nox-specific inhibitor were evaluated in Epstein-Barr virus (EBV)-positive Raji BL cells in comparison with EBV-negative Ramos BL cells. To evaluate Nox enzyme expression in Raji and Ramos BL cells, polymerase chain reaction (PCR) and western blot analysis were performed. To verify the intracellular signaling mechanism of the Nox inhibitor-induced apoptosis of Raji cells, WST-1 assay, trypan blue exclusion method, flow cytometry, PCR, western blotting, and bromodeoxyuridine staining were conducted. Experiments using the pan-caspase inhibitor z-VAD, reactive oxygen species scavenger N-acetyl-L-cysteine (NAC), and Bim inhibitor 1 were performed. PCR and western blot results showed that Nox isoform enzymes were highly expressed in EBV-positive BL Raji cells compared with EBV-negative BL Ramos cells. The Nox2 inhibitor induced apoptosis of Raji cells in time- and dosedependent manners. The Nox2 inhibitor also caused up-regulation of Bim and Noxa, down-regulation of Mcl-1, translocation of Bax, release of cytochrome c, and caspase cascade activation, resulting in apoptosis. Furthermore, z-VAD, NAC, and BI-1 effectively blocked the Nox2 inhibitor-induced apoptosis of Raji cells. Taken together, these results provide a novel insight into the mechanism of Nox inhibitor-induced apoptosis and evidence for Nox as a therapeutic target to treat EBV-positive malignancies.