Black Hairy Tongue Associated with Erlotinib Treatment in a Patient with Advanced Lung Cancer

Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor (EGFR). There have been many reports of the mucocutaneous side effects related to several EGFR inhibitors (EGFRIs). However, no case of black hairy tongue (BHT) associated with EGFRI has been reported. Herein, we report the first case of erlotinib-induced BHT in a 61-year-old man with advanced lung cancer. Considering recent use of EGFRIs worldwide, dermatologists should recognize the possible occurrence of BHT associated with EGFRIs such as erlotinib

Milia-like Idiopathic Calcinosis Cutis Occurring in a Toddler Born as a Premature Baby

Milia-like idiopathic calcinosis cutis (MICC) is characterized by smooth, firm, whitish papules resembling milia. Histologically, it appears as a well-defined, round, basophilic nodule within the upper dermis. Although the etiology and treatment remain unclear, it may resolve spontaneously. Some cases have been associated with Down syndrome, and the mean age of MICC patients was 9.9 years old. Herein, we report a rare case of MICC that was not associated with Down syndrome. Noticeably, the patient, a toddler, was born as a premature baby and had an ischemic injury on the right foot at birth. However, the lesions appeared on both feet, including the non-injured left foot. Otherwise he was healthy. After a 21-month follow-up period, the lesions had almost disappeared without any treatment

Erythematous Granuloma Annulare

Granuloma annulare (GA) is a common, benign, chronic inflammatory disorder, which is characterized by grouped papules in an enlarging annular shape. It has been described in several clinical subtypes, including localized, generalized, subcutaneous, perforating, and erythematous types. Even though generalized, subcutaneous, and perforating types of GA are unusual, there are several reports of those types. However, erythematous or patch GA, has not been reported yet in the Korean literature. Herein, we report a 42-year-old woman with pruritic erythematous patches, which occurred on the extremities without preceding event, and showed typical clinical and histopatologic findings of erythematous GA

Primary Localized Cutaneous Nodular Amyloidosis Following Local Trauma

Primary localized cutaneous nodular amyloidosis (nodular amyloidosis) is a rare and distinct type of amyloidosis, in which amyloid L deposition is limited to the skin and typically manifested as a tumefactive nodule on the acral sites. However, the definite cause of nodular amyloidosis is still unknown. Although it is relatively well known that the amyloid deposits in nodular amyloidosis originate from immunoglobulin light chains secreted by local plasma cells, traumatic injury to the skin has rarely been recognized as a triggering factor of nodular amyloidosis. Herein, we present a case of a 50-year-old male patient with primary localized cutaneous nodular amyloidosis, which occurred after local trauma, and discuss the relationship between traumatic damage and dermal amyloid L deposition

NPM1 as a potential therapeutic target for atypical teratoid/rhabdoid tumors

Background Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant brain tumors with inactivation of the SMARCB1 gene, which play a critical role in genomic transcriptional control. In this study, we analyzed the genomic and transcriptomic profiles of human AT/RTs to discover new druggable targets. Methods Multiplanar sequencing analyses, including whole exome sequencing (WES), single nucleotide polymorphism (SNP) arrays, array comparative genomic hybridization (aCGH), and whole transcriptome sequencing (RNA-Seq), were performed on 4 AT/RT tissues. Validation of a druggable target was conducted using AT/RT cell lines. Results WES revealed that the AT/RT genome is extremely stable except for the inactivation of SMARCB1. However, we identified 897 significantly upregulated genes and 523 significantly downregulated genes identified using RNA-Seq, indicating that the transcriptional profiles of the AT/RT tissues changed substantially. Gene set enrichment assays revealed genes related to the canonical pathways of cancers, and nucleophosmin (NPM1) was the most significantly upregulated gene in the AT/RT samples. An NPM1 inhibitor (NSC348884) effectively suppressed the viability of 7 AT/RT cell lines. Network analyses showed that genes associated with NPM1 are mainly involved in cell cycle regulation. Upon treatment with an NPM1 inhibitor, cell cycle arrest at G1 phase was observed in AT/RT cells. Conclusions We propose that NPM1 is a novel therapeutic target for AT/RTs.This research was supported by the Bio & Medical Technology Development Program (NRF-2018M3A9H3021707) and the Basic Science Research Program (NRF-2019R1A2C2005144) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT of Republic of Korea and a grant from the Samsung SDS. The funders collaboratively provided grants to complete the sequencing, data analysis, in vitro experiments, and publication

In vivo bioluminescence imaging for leptomeningeal dissemination of medulloblastoma in mouse models

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background The primary cause of treatment failure in medulloblastomas (MB) is the development of leptomeningeal dissemination (seeding). For translational research on MB seeding, one of the major challenges is the development of reliable experimental models that simulate the seeding and growth characteristics of MBs. To overcome this obstacle, we improved an experimental mouse model by intracisternal inoculation of human MB cells and monitoring with in vivo live images. Methods Human MB cells (UW426, D283 and MED8A) were transfected with a firefly luciferase gene and a Thy1.1 (CD90.1) marker linked with IRES under the control of the CMV promoter in a retroviral DNA backbone (effLuc). The MB-effLuc cells were injected into the cisterna magna using an intrathecal catheter, and bioluminescence images were captured. We performed histopathological analysis to confirm the extent of tumor seeding. Results The luciferase activity of MB-effLuc cells displayed a gradually increasing pattern, which correlated with a quantitative luminometric assay. Live imaging showed that the MB-effLuc cells were diffusely distributed in the cervical spinal cord and the lumbosacral area. All mice injected with UW426-effLuc, D283-effLuc and MED8A-effLuc died within 51 days. The median survival was 22, 41 and 12 days after injection of 1.2 × 106 UW426-effLuc, D283-effLuc and MED8A-effLuc cells, respectively. The histopathological studies revealed that the MB-effLuc cells spread extensively and diffusely along the leptomeninges of the brain and spinal cord, forming tumor cell-coated layers. The tumor cells in the subarachnoid space expressed a human nuclei marker and Ki-67. Compared with the intracerebellar injection method in which the subfrontal area and distal spinal cord were spared by tumor cell seeding in some mice, the intracisternal injection model more closely resembled the widespread leptomeningeal seeding observed in MB patients. Conclusion The results and described method are valuable resources for further translational research to overcome MB seeding

Subgroup-specific prognostic signaling and metabolic pathways in pediatric medulloblastoma

Background Using a pathway-focused approach, we aimed to provide a subgroup-specific basis for finding novel therapeutic strategies and further refinement of the risk stratification in pediatric medulloblastoma. Method Based on genome-wide Cox regression and Gene Set Enrichment Analysis, we investigated prognosis-related signaling pathways and core genes in pediatric medulloblastoma subgroups using 530 patient data from Medulloblastoma Advanced Genomic International Consortium (MAGIC) project. We further examined the relationship between expression of the prognostic core genes and frequent chromosome aberrations using broad range copy number change data. Results In SHH subgroup, relatively high expression of the core genes involved in p53, PLK1, FOXM1, and Aurora B signaling pathways are associated with poor prognosis, and their average expression synergistically increases with co-occurrence of losses of 17p, 14q, or 10q, or gain of 17q. In Group 3, in addition to high MYC expression, relatively elevated expression of PDGFRA, IGF1R, and FGF2 and their downstream genes in PI3K/AKT and MAPK/ERK pathways are related to poor survival outcome, and their average expression is increased with the presence of isochromosome 17q [i(17q)] and synergistically down-regulated with simultaneous losses of 16p, 8q, or 4q. In Group 4, up-regulation of the genes encoding various immune receptors and those involved in NOTCH, NF-κB, PI3K/AKT, or RHOA signaling pathways are associated with worse prognosis. Additionally, the expressions of Notch genes correlate with those of the prognostic immune receptors. Besides the Group 4 patients with previously known prognostic aberration, loss of chromosome 11, those with loss of 8q but without i(17q) show excellent survival outcomes and low average expression of the prognostic core genes whereas those harboring 10q loss, 1q gain, or 12q gain accompanied by i(17q) show bad outcomes. Finally, several metabolic pathways known to be reprogrammed in cancer cells are detected as prognostic pathways including glutamate metabolism in SHH subgroup, pentose phosphate pathway and TCA cycle in Group 3, and folate-mediated one carbon-metabolism in Group 4. Conclusions The results underscore several subgroup-specific pathways for potential therapeutic interventions: SHH-GLI-FOXM1 pathway in SHH subgroup, receptor tyrosine kinases and their downstream pathways in Group 3, and immune and inflammatory pathways in Group 4.This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1420020), Mid-career Researcher Program through the National Research Foundation (NRF) grant funded by the Korea government (Ministry of Science and ICT, 2017R1A2B2008422), and NRF grants funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2012R1A1A1042953 and 2015R1A4A1041219). The funding bodies had no role in the design of the study, collection, analysis, and interpretation of data nor in writing the manuscript

Cholestatic Hepatitis and Thrombocytosis in a Secondary Syphilis Patient

The incidence of acute hepatitis in syphilis patient is rare. First of all, our patient presented with hepatitis comorbid with thrombocytosis. To our knowledge, this is only the second report of syphilitic hepatitis with thrombocytosis. The 42-yr-old male complained of flulike symptoms and skin eruptions on his palms and soles. Laboratory findings suggested an acute hepatitis and thrombocytosis. Serologic test results were positive for VDRL. He recovered from his symptoms and elevated liver related enzymes with treatment. Because syphilitic hepatitis can present without any typical signs of accompanying syphilis, syphilis should be considered as a possible cause in acute hepatitis patients

Clinical practice guideline for the diagnosis and treatment of pediatric obesity: recommendations from the Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology Hepatology and Nutrition

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: (1) definition and diagnosis of overweight and obesity in children and adolescents; (2) principles of treatment of pediatric obesity; (3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; (4) pharmacotherapy; and (5) bariatric surgery