J.H. Lee

Genetic analysis of the LKB1/STK11 gene in hepatocellular carcinomas

The tumour suppressor gene, LKB1/STK11, has been mapped to chromosome 19p13, a region showing frequent allelic loss in various human cancers, including hepatocellular carcinoma (HCC). Additionally, LKB1 physically associates with p53 and regulates p53-dependent apoptotic pathways. To investigate whether genetic alterations of LKB1 could be involved in the tumorigenesis of HCC, we analysed the genetic alterations of the LKB1 and p53 genes in seven dysplastic nodules and 80 HCCs. We found one LKB1 missense mutation, CCG-->CTG (Pro-->Leu) at codon 281 within the kinase domain. We also found allelic loss in six of 27 (22%) informative HCC cases and all of them were HBV-positive cases. In addition, we detected seven missense, one nonsense and one silent mutations (nine of 80, 11%) of p53 in HCCs only. These results suggest that genetic alterations of the LKB1 or p53 genes may play an important role in tumour development or progression of a sub-set of HCCs, and may also provide alternative mechanisms to protect the HCC cell from p53-dependent apoptosis.

p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and multiple mutations

We analyzed the p53 protein expression and gene mutations to evaluate the role of ultraviolet radiation or other carcinogens, and possible racial differences in 17 samples from 12 Korean patients with Bowens disease. A simple microdissection technique was used to collect the tumor cells selectively. p53 protein expression was found in eight of 17 (47%) samples. Abnormalities in polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were observed in 16 (94%) samples. A total of 14 missense mutations were detected in eight (47%) samples; 11 were clustered in exon 5 and the remaining three were located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but no CC to TT transitions, UV-fingerprint mutations were observed. Multiple mutations were present in two cases and double mutation in a single case. Each lesion in multiple Bowens disease showed different mutations and was suggested to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected in four out of 15 (27%) informative samples. Clustering of mutations in exon 5 suggests the role of another carcinogen in Koreans or Asians other than the UVR. Microdissection would increase the detection rate of the p53 gene mutations and LOH not only in skin cancer but also in precancerous lesions.

Generalized atrophic benign epidermolysis bullosa – poor prognosis associated with chronic renal failure

Generalized atrophic benign epidermolysis bullosa (GABEB) is an autosomal recessive form of junctional epidermolysis bullosa, with milder clinical features than the Herlitz subtype. A 25‐year‐old man presented with the clinical and histological findings of GABEB. At the initial visit, laboratory tests revealed that he also had chronic renal failure (CRF). Usually, GABEB has a good prognosis. However, in this case, the patient had CRF as an associated complication. He died of an intracranial haemorrhage combined with sepsis after 3u2003weeks of hospitalization. This case suggests that renal complications can occur in this relatively mild form of epidermolysis bullosa, and may contribute to morbidity and premature mortality.

Incidence, prevalence, and mortality of Adamantiades‐Behçet's disease in Korea: a nationwide, population‐based study (2006–2015)

The epidemiology of Adamantiades‐Behçets disease varies among ethnic populations worldwide. Trends in the incidence of Adamantiades‐Behçets disease have not been investigated based on the Korean National Health Insurance database.

201 Transcriptome analysis of CD133-positive stem cells and prognostic value of survivin in colorectal cancer

BACKGROUND/AIMnCD133 is an important, but not exclusive, biomarker of colorectal cancer (CRC) stem cells.nnnMATERIALS AND METHODSnIn order to identify other CRC stem cell-specific genes, we performed a comparative expression profiling of CD133(+) and CD133(-) cell populations in primary and metastatic tumors from four patients with CRC. CD133(+) and CD133(-) CRC cells were isolated using MagSweeper and used for whole-transcriptome analysis with RNA-Seq.nnnRESULTSnWe found that in CD133(+) cells, 17 genes (RNASE2, PRB2, IL4, MGC27382, CLEC4C, SALL3, GIMAP1, ISG15, LOC728875, ZIK1, ICAM2, CCDC7, CDYL2, LRRC2, ZEB1, OSTF1 and CCDC144B) were significantly up-regulated compared to CD133(-) CRC cells. Among them, IL4 has been known as an inducer of survivin implicated in the survival and proliferation of cancer cells. However, the prognostic value of survivin in CRC is controversial. We evaluated survivin expression in formalin-fixed paraffin-embedded tumor samples of 188 patients with CRC by immunohistochemistry. Survivin over-expression was detected in 85 patients (45.2%) and was significantly associated with primary tumor sites (p=0.028), lymph node metastasis (p=0.029) and advanced III/IV CRC stages (AJCC 7; p=0.001). Furthermore, survivin up-regulation correlated with reduced disease-free survival (DFS; p=0.021) and overall survival (OS; p<0.000) and was proved to be an independent prognostic factor for both DFS and OS in multivariate analysis.nnnCONCLUSIONnOur data suggest that CD133(+) CRC stem cells have a distinct expression pattern and that survivin, up-regulated by differentially expressed IL-4, is a candidate biomarker for the prediction of recurrence and survival in CRC.

Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population‐based study

The prevalence of hidradenitis suppurativa (HS) in Asia is unknown. The associations between HS and other autoimmune disorders have rarely been reported.

A hyaluronic acid-based microneedle patch to treat psoriatic plaques: A pilot open trial.

DEAR EDITOR, Psoriasis is a common, chronic, relapsing, inflammatory skin disease characterized by multiple erythematous papules and plaques with silvery scales. It affects 0 5–3% of the world’s population. Recently, great advances have been made in the treatment of psoriasis, including the introduction of targeted biological agents. However, topical treatment remains important; most patients have mild disease affecting < 2% of the body surface area. Unfortunately, topical treatment is oily and sticky, and it takes time to reach full therapeutic effect, which results in poor patient compliance and consequently low therapeutic efficacy. The microneedle patch is a new drug delivery method that can effectively improve transdermal drug delivery. In this present study, we assessed whether a novel hyaluronic acid (HA)-based microneedle patch enhanced the therapeutic effects of topical agents in psoriasis. Ten patients with psoriatic plaques resistant to topical calcipotriol–betamethasone ointment (Daivobet ; LEO Pharma, Ballerup, Denmark) therapy for at least 4 weeks were enrolled from 1 May to 31 July 2016. One or more resistant psoriatic plaques were selected, and microneedle patches were placed over the thickest areas of the plaques after application of topical calcipotriol–betamethasone ointment. The patches were applied once daily at night for 1 week and removed the following morning. The patches were 26 9 26-mm-sized HA-

Impact of paraaortic lymphadenectomy for endometrial cancer with positive pelvic lymph nodes: A Korean Radiation Oncology Group study (KROG 13-17)

AIMnWe investigated the role of paraaortic lymph node dissection (PALND) in patients with stage IIIC1 endometrial carcinoma after surgery followed by adjuvant radiotherapy (RT) alone or chemoradiotherapy (CTRT).nnnMETHODSnWe performed a subgroup analysis in 151 patients treated with adjuvant pelvic RT. Paraaortic-recurrence free survival, disease-free survival (DFS) and overall survival (OS) were analyzed.nnnRESULTSnIn adjuvant RT alone, PALND was significantly related to reduced risk of paraaortic recurrence (0% vs. 17.1%) and distant metastasis (4.5% vs. 19.5%) compared with the no PALND group. PALND affected 5-year DFS (90.2% vs. 58.9%, pxa0=xa00.016) and OS (100% vs. 83.1%, pxa0=xa00.022). For the CTRT group, the paraaortic recurrence rate was 19.5% for the no PALND group and 12.8% for the PALND group (pxa0=xa00.682). Of patients who underwent PALND in the CTRT group, less extensive PALND was significantly related to increased paraaortic recurrence (≤10 vs. >10 dissected LNs, 17.1% vs. 0%). In the no PALND group (nxa0=xa082), 5-year paraaortic-recurrence free survival was 79.4% for the CTRT group and 76.2% for the RT alone group (pxa0=xa00.941). In multivariate analysis, PALND was significantly associated with reduced risk of disease-specific death (HR, 0.50; 95% CI, 0.26-0.96; pxa0=xa00.037).nnnCONCLUSIONnPALND provided excellent paraaortic control and improved outcome in stage IIIC1 endometrial cancer with favorable tumor features treated with adjuvant RT alone. Less extensive PALND was associated with significantly increased paraaortic recurrence in patients with advanced tumor features treated with adjuvant CTRT. Combined CTRT did not affect disease control in the paraaortic region compared with RT alone.

Expression of YAP and TAZ in molluscum contagiosum virus infected skin

The Hippo signaling pathway, which is highly conserved in organisms ranging from Drosophila to mammals, plays a key role in organ size control, cellular proliferation, survival and tumorigenesis1 Yes-associated protein (YAP) is the major downstream effector of Hippo signaling pathway and transcriptional co-activator with PDZ-binding motif (TAZ) is a YAP paralog. Recently, Zhang etxa0al. found that YAP/TAZ acts as natural inhibitors of TANK binding kinase 1 (TBK1), which is a key component for cytosolic nucleic acid sensing antiviral defense and antiviral physiology2 This article is protected by copyright. All rights reserved.

Prevalence and incidence of chronic spontaneous urticaria in the entire Korean adult population

Ethnic differences and temporal trends in the epidemiology of chronic spontaneous urticaria (CSU) are not well understood, especially in East Asia.1-3 The aim of our study was to investigate trends in the prevalence and incidence of CSU among adult Korean subjects from 2006 to 2014 using a nationwide, population-based study. n nThis article is protected by copyright. All rights reserved.