Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. @*Materials and Methods@#We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. @*Results@#Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. @*Conclusion@#Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. @*Materials and Methods@#To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. @*Results@#Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. @*Conclusion@#We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Encephalitis with Anti-SOX1 Antibodies Presenting with New-Onset Refractory Status Epilepticus

No abstract available.

Refractory Nonconvulsive Status Epilepticus with Favorable Outcome in a Patient with Marchiafava-Bignami Disease

No abstract available.

Improved Bulbar Function in Amyotrophic Lateral Sclerosis after Nuedexta (Dextromethorphan and Quinidine) Treatment

Nuedexta (dextromethorphan and quinidine) is an Food and Drug Administration approved medication for pseudobulbar affect. Interestingly, this drug was recently reported to improve speech, swallowing, and the ability to handle oral secretions along with emotional lability in amyotrophic lateral sclerosis (ALS) patients with bulbar symptoms. We report a Korean ALS patient whose bulbar function improved after administering Nuedexta for 6 months, extending therapeutic choice of approach in treating ALS patients.

Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress Glioblastoma Tumor Growth / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. MATERIALS AND METHODS: We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. RESULTS: By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. CONCLUSION: In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.

A Case of Persistent Cow's Milk Allergy Accompanying Atopic Dermatitis / 대한피부과학회지

No abstract available.

Fibro-Osseous Pseudotumor of the Digit Presenting as an Enlarging Erythematous Subungual Nodule

No abstract available.

Two Cases of Successful Treatment of Refractory Chronic Inflammatory Skin Disease, Atopic Dermatitis and Psoriasis with Oral Alitretinoin

No abstract available.

A Case of Eccrine Spiradenoma: A Rarely Seen Soft Tissue Tumor on the Extensor Surface of Arm

No abstract available.

Intense Pulsed Light and Q-Switched 1,064-nm Neodymium-Doped Yttrium Aluminum Garnet Laser Treatment for the Scarring Lesion of Discoid Lupus Erythematosus

Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus that can cause permanent scarring. Treatment of DLE includes protection from sunlight and artificial sources of ultraviolet light, as well as systemic and topical medications. The first-line standard therapies are antimalarials and topical steroids. Other systemic therapies include systemic steroid, azathioprine, dapsone, and immunosuppressive agents. Topical tacrolimus and pimecrolimus have also been evaluated. Recent studies reported that several treatments, including pulsed dye laser, CO₂ laser, intense pulsed light (IPL), and 1,064-nm long-pulse neodymium-doped yttrium aluminum (Nd:YAG) have been used for the cosmetic treatment of DLE. Here, we report a case of a DLE scar that was successfully treated with a combination therapy of IPL and Q-switched 1,064-nm Nd:YAG laser.

Prevalence of Pork Allergy in Korea / 대한피부과학회지

BACKGROUND: Pork is one of the most widely consumed meats in Korea. With increased consumption of pork, it has become one of the most common causes of food allergy in Korea. However, actual data on the prevalence of pork allergy in Korea are limited. OBJECTIVE: The aim of this study was to estimate the prevalence of pork allergy in Korea. METHODS: The outpatient attendees of the dermatology department of Kangnam Sacred Heart Hospital were randomly screened and assessed for a self-reported history of pork allergy through face-to-face interviews and self-administered questionnaires. Blood samples were taken from the patients to measure serum pork-specific IgE. Based on their history and laboratory results, patients were further examined by skin prick test (SPT) and open oral food challenge (OFC) tests. RESULTS: Five-hundred participants answered the screening questionnaire. Among all participants, nine (1.8%) participants claimed to have experienced adverse reactions to pork previously. Among 100 participants who underwent blood sampling, five (5%) participants had elevated level of serum IgE specific to pork. However, among nine participants with self-reported pork allergy, two participants (0.22%) showed a positive reaction on the open OFC test. CONCLUSION: Some participants claimed to have a history of adverse reaction related to pork intake; however, few of them showed positive results in allergy tests. We therefore conclude that the prevalence of pork allergy is extremely low in Korea.

Cutaneous Mixed Infection of Mycobacterium fortuitum and Mycobacterium intracellulare after a Fat Graft / 대한피부과학회지

Atypical mycobacteria, widely distributed in nature, are opportunistic infection strain, rare pathogen in immunocompetent patients. Recently, the increase of invasive cosmetic treatment and surgery has increased the infection of atypical mycobacteria. We report a case of cutaneous infection by Mycobacterium fortuitum and Mycobacterium intracellulare that occurred after a fat graft. A 62-year-old female patient presented painful, erythematous nodules and purulent discharge on her face after a fat graft. A skin biopsy and culture were performed. Polymerase chain reaction-hybridization to identify mycobacterium other than tuberculosis revealed M. fortuitum and M. intracellulare. The patient was treated with clarithromycin, rifampicin, and ethambutol for 1 month after excision and drainage of pus, after which the skin lesions improved. In cases of refractory cutaneous infection after an invasive cosmetic procedure, atypical mycobacterial infection should be suspected.

Herpes Zoster Duplex Unilateralis: Two Cases and Brief Literature Review

Cases involving dermatomal herpes zoster in two or more locations are rare, especially in immunocompetent patients. When two noncontiguous dermatomes are involved, if affected unilaterally, it is called herpes zoster duplex unilateralis; if bilaterally, bilateralis. Here, we report two cases of herpes zoster duplex unilateralis. A 66-year-old man presented with painful erythematous grouped vesicles on his left scalp, forehead, trunk, and back (left [Lt.] V1, Lt. T8). Histologic findings were consistent with herpetic infection. A 33-year-old woman presented with painful erythematous grouped vesicles and crust on her left forehead and neck (Lt. V1, Lt. C5). Both patients were treated with oral administration of famcyclovir 750 mg/day for seven days.

Effect of a Histamine-free Diet in Adult Patients with Atopic Dermatitis / 대한피부과학회지

BACKGROUND: For atopic dermatitis (AD), the causal relationship between food and exacerbation is relatively weak in adults compared to children. However, many adult patients report food-related aggravation of AD, and some may have histamine intolerance. OBJECTIVE: The aim of this study was to evaluate the role of ingested histamine and investigate the effect of a histamine-free diet in adult patients with AD. METHODS: Adult patients with AD and healthy controls were enrolled. Patients were prohibited from eating foods with high amounts of histamine for 4 weeks. There were no diet restrictions for the controls. The eczema area and severity index (EASI) and degree of pruritus using the visual analogue scale (VAS) were evaluated. Plasma histamine levels and diamine oxidase (DAO) activity were determined, and compared with those of the control group. RESULTS: Seventeen adult patients were recruited and of these, 12 completed the 4-week histamine-free diet. There was no significant difference in the basal plasma histamine levels between the patients and controls. Basal DAO activity was significantly higher in patients compared to the controls. There was no significant difference in plasma histamine levels after the histamine free-diet and DAO activity was not altered. Moreover, EASI and VAS were similar before and after the histamine-free diet. CONCLUSION: Ingested histamine might be unrelated with AD severity and a histamine-free diet is unhelpful for adult patients with AD.

Oral Allergy Syndrome to Hazelnuts / 대한피부과학회지

No abstract available.

Induction of a Hardening Phenomenon and Quantitative Changes of Ceramides in Stratum Corneum

BACKGROUND: Hardening phenomenon of human skin after repeated exposure to the irritants is well-known, but the precise mechanism remains elusive. OBJECTIVE: To modify the previous experimental model of hardening phenomenon by repeated applications of two different concentrations of sodium lauryl sulfate (SLS) solutions to Korean healthy volunteers and to investigate the quantitative changes of ceramides in stratum corneum before and after chronic repeated irritation. METHODS: Eight hundred microliters of distilled water containing 0.1% and 2% SLS was applied for 10 minutes on the forearm of 41 healthy volunteers for 3 weeks. After an intervening 3-week rest, 24-hour patch tests with 1% SLS were conducted on previously irritated sites. Transepidermal water loss (TEWL), erythema index and quantity of ceramide were measured in the stratum corneum before and after irritation. RESULTS: TEWL values on the sites preirritated with 2% SLS were lower than those with 0.1% SLS. Hardening phenomenon occurred in 24 volunteers at day 44. The changes in ceramide levels were not significantly higher in the hardened skin than in the non-hardened skin. CONCLUSION: Repetitive stimulation with a higher concentration of SLS can more easily trigger skin hardening.

Lack of Association of Plasma Histamine with Diamine Oxidase in Chronic Idiopathic Urticaria

BACKGROUND: Chronic idiopathic urticaria (CIU) is considered a complex and multifactorial disease. Excessive histamine intake may induce an attack of urticaria. The main enzyme for histamine metabolism is diamine oxidase (DAO). OBJECTIVE: Plasma histamine concentrations and DAO activities were evaluated to determine whether there are abnormalities in the histamine metabolism of CIU patients. METHODS: Seventy-five CIU patients and twenty-five healthy control subjects were included in the study. Blood was taken from all subjects to measure plasma levels of the histamine and DAO. RESULTS: Mean plasma histamine levels were significantly higher in CIU patients (11.59+/-10.98 nM) than in the control subjects (8.75+/-2.55 nM) (p=0.04). Mean DAO activities were lower in patients of CIU (80.86+/-26.81 histamine degrading unit [HDU]/ml) than in the controls (81.60+/-9.67 HDU/ml), but without significant difference. In 15 CIU patients with gastrointestinal symptoms, the mean histamine concentration was higher (12.43+/-7.97 nM) and DAO activity was lower (77.93+/-27.53 HDU/ml) than in the remaining 60 CIU patients without gastrointestinal symptoms (11.38+/-11.67 nM and 81.58+/-26.82 HDU/ml), without significant difference. The relationship between DAO activity and plasma histamine concentrations showed a significant negative linear value (p=0.001). There were no significant relationships between plasma histamine concentrations and symptom severity score. CONCLUSION: In CIU patients, a high plasma histamine concentration may not be explained by DAO activity. CIU patients with gastrointestinal (GI) symptoms showed no significantly lower DAO activity. Larger group studies are required to elucidate the relationship between plasma histamine concentrations and DAO activity, especially of CIU patients with GI symptomsto understand the difference in CIU patients with and without GI symptoms.

Food Hypersensitivity in Patients with Childhood Atopic Dermatitis in Korea

BACKGROUND: It is well known that atopic dermatitis (AD) is related to food hypersensitivity, although its prevalence varies among several studies according to age group, severity, country, survey time, and test method. OBJECTIVE: To examine the prevalence and status of food hypersensitivity among childhood AD patients in Korea. METHODS: A total of 95 patients were enrolled in the study. The history of food hypersensitivity was collected by interviews. The severity of AD was evaluated by eczema area and severity index (EASI). We took blood samples to measure serum total and food-specific immunoglobulin E (IgE) levels. Based on the histories and serum IgE levels, open oral food challenge (OFC) testing was performed to confirm food hypersensitivity. RESULTS: Forty-two (44.2%) of the 95 AD patients had histories of food hypersensitivity. They reported that the most common suspicious foods were egg (n=13, 13.7%), pork (n=9, 9.5%) and cow milk (n=8, 8.4%). The mean EASI score was 16.05+/-9.76. Thirty-nine (41.1%) of the 95 patients showed elevated serum food-specific IgE levels. The specific IgE levels were elevated for egg (n=17, 17.9%), milk (n=12, 12.6%), peanut (n=10, 10.5%) and wheat (n=8, 8.4%). Fifty-one (53.8%) of 95 patients underwent open OFC, and only 7 (13.7%) of these patients showed positive reactions. CONCLUSION: The overall prevalence of food hypersensitivity in patients with childhood AD in Korea was 8.3% (7/84). The most common foods causing food hypersensitivity were egg and milk. Among the foods causing hypersensitivity, AD patients in Korea often underestimated peanut, while they overestimated pork.

Tear Filim Changes and Ocular Surface Characteristics in Patients with Psoriasis Vulgaris / 대한피부과학회지

BACKGROUND: Psoriasis is associated with several extracutaneous manifestations. Signs and symptoms of eye may be subtle and overlooked. OBJECTIVE: Our purpose was to identify tear film functions and ocular surface characteristics associated psoriasis. METHODS: We examined 20 patients with psoriasis and 20 patients healthy volunteers. In addition to complete dermatological examination, tear film function, meibomian gland obstruction, Shirmer test, as well as conjunctival impression cytology grades and goblet cell density. RESULTS: Patients with psoriasis had tear film break-up time of 7.7+/-3.1 seconds. The grade of fluorescein test in patients with psoriasis was significantly higher than the grades in controls. And in impression cytology patients group showed the higher grade of epithelial metaplasia and lower density of goblet cells. But The significant differences were not found in Shirmer test and meibomian gland obstruction. CONCLUSION: Our findings showed that patients with psoriasis have high rate of dye eye disease. Dermatologists consider the possibility of ocular manifestations of patients with psoriasis and consultation with the ophthalmologists.