Inhibition of TNFα-interacting protein α (Tipα)-associated gastric carcinogenesis by BTG2(/TIS21) via downregulating cytoplasmic nucleolin expression

To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2(/TIS21)), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach. Expression was increased in the mucous epithelium following H. pylori infection in contrast to its loss in human gastric adenocarcinoma. Indeed, adenoviral transduction of BTG2(/TIS21) significantly inhibited Tipα activity in MKN-1 and MGT-40, human and mouse gastric cancer cells, respectively, thereby downregulating tumor necrosis factor-α (TNFα) expression and Erk1/2 phosphorylation by reducing expression of nucleolin, a Tipα receptor. Chromatin immunoprecipitation proved that BTG2(/TIS21) inhibited Sp1 expression and its binding to the promoter of the nucleolin gene. In addition, BTG2(/TIS21) expression significantly reduced membrane-localized nucleolin expression in cancer cells, and the loss of BTG2(/TIS21) expression induced cytoplasmic nucleolin availability in gastric cancer tissues, as evidenced by immunoblotting and immunohistochemistry. Higher expression of BTG2 and lower expression of nucleolin were accompanied with better overall survival of poorly differentiated gastric cancer patients. This is the first report showing that BTG2(/TIS21) inhibits nucleolin expression via Sp1 binding, which might be associated with the inhibition of H. pylori-induced carcinogenesis. We suggest that BTG2(/TIS21) is a potential inhibitor of nucleolin in the cytoplasm, leading to inhibition of carcinogenesis after H. pylori infection.

Compound K, a Metabolite of Ginsenosides, Attenuates Collagen-induced Arthritis in Mice

OBJECTIVE: Although several ginsenosides have been reported to have anti-arthritic activity, few in vivo studies of the anti-arthritic effects of compound K (CK), a major metabolite of ginsenosides, have been conducted. Therefore, we investigated the preventative and therapeutic effects of CK on collagen-induced arthritis (CIA). METHODS: CK was administered to CIA mice preventively and therapeutically and post-treatment bone microarchitectural characteristics, histopathological changes, and serum levels of anti-collagen antibodies, tumor necrosis factor-alpha, and interleukin (IL)-17 were investigated. We also examined cytokine production by type II collagen (CII)-stimulated splenocytes and mRNA expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase (TIMP)-1, receptor activator of nuclear factor-kappaB ligand (RANKL), and osteoprotegerin (OPG) in the joint tissues. RESULTS: CK reduced the severity of CIA preventively and therapeutically (all p<0.05). Additionally, CK dose-dependently decreased histopathological signs of arthritis and improved microarchitectural characteristics (all p<0.05) at 10 to 20 mg/kg/d in CIA mice. CK treatment significantly decreased the serum levels of anti-CII immunoglobulin G (p<0.01) and the secretion of interferon-gamma and IL-2 from stimulated splenocytes (all p<0.05). Furthermore, MMP-3/TIMP-1 and RANKL/OPG ratios were suppressed in CK treated mice (all p<0.01). CONCLUSION: CK attenuated CIA via suppression of the humoral immune response and modulation of joint-destructive mediators. These results suggest that CK has therapeutic potential in rheumatoid arthritis.

A Case of Epithelioid Blue Nevus

No abstract available.

Spontaneous Regression of Merkel Cell Carcinoma / 대한피부과학회지

Merkel cell carcinoma is a malignant neuroendocrine tumor with a high rate of recurrence and metastasis. However, approximately 23 cases of spontaneous regression have been reported. We report a case of Merkel cell carcinoma which showed spontaneous regression. The patient was an 84-year-old male with a large red-colored, hemispheric tumor on the left inner thigh which had been presented for a year. We planned to perform surgery, but the tumor suddenly started to regress spontaneously. The size of the tumor decreased, the surface was flattened, and the color changed from red to brown. The lesion finally appeared as a brownish flat plaque. Excision of the regressed tumor was performed; immunohistopathological analysis showed CD3+ T cells infiltrating around the regressed merkel cell carcinoma.

Extramammary Paget Disease: Minimal Surgical Therapy

BACKGROUND: Extramammary Paget disease (EMPD) is an uncommon malignant neoplasm affecting apocrine gland-bearing skin which usually occurs in the anogenital area of patients older than 50 years. Although Mohs micrographic surgery (MMS) is recommended for the treatment of EMPD, wide local excision has also been performed by many other surgeons including dermatosurgeons. However, the extent of an adequate resection margin is still under debate. OBJECTIVE: The efficacy of minimal surgical therapy consisting of a wide excision combined with preoperative multiple scouting biopsies and postoperative topical imiquimod was investigated for the treatment of EMPD in Korean patients. METHODS: Between 2006 and 2012, 10 patients with primary EMPD were treated with wide surgical excision, with a surgical margin of less than 2.5 cm. Multiple preoperative scouting biopsies and postoperative topical imiquimod were also performed to delineate the lesional boundaries and to reduce the recurrence rate. RESULTS: During the 6-year follow-up period, complications and recurrences were not observed. CONCLUSION: Minimal surgical therapy may be an effective alternative when MMS is unavailable.

Papular Elastorrhexis in Down's Syndrome / 대한피부과학회지

No abstract available.

Necrobiotic Xanthogranuloma with Monoclonal Gammopathy / 대한피부과학회지

Necrobiotic xanthogranuloma (NXG) is a rare, progressive, histiocytic disease characterized by destructive cutaneous lesions, a close association with paraproteinemia, multiple myeloma, hypertension, and multiple extracutaneous manifestations. Multiple indurated yellow-red plaques or nodules are commonly present in this disorder. The pathogenesis of NXG is poorly understood. Histopathologically, NXG features with hyaline necrosis or necrobiosis are present. We describe a patient with typical cutaneous and histologic findings of NXG with an associated monoclonal gammopathy.

Immunohistochemical Study on the Expression of Desmocollin 1 during Skin Development / 대한피부과학회지

BACKGROUND: Desmocollins (Dsc) are calcium-dependent transmembrane glycoproteins of desmosomes that are important in the junction complex of epidermis and maintain structural integrity of the skin from external stressors. Among three Dscs (Dsc 1, 2, 3), Dsc 1 and 3 are distributed on skin. OBJECTIVE: The purpose of this study was to observe the Dsc 1 distribution pattern on the skin and oral mucosa during fetal development. METHODS: Skin was obtained from the sole and scalp of 33 fetuses, ranging from 10 to 37 weeks of gestational age. Immunohistochemical staining was performed on the paraffin-embedded tissue using a Dsc 1 monoclonal antibody. RESULTS: Dsc 1 was expressed in the suprabasal layer but not in the basal layer of the epidermis of the sole at the 10th week of gestation. Thereafter, Dsc 1 expression further increased in the suprabasal layer with initiation of stratification and increased gradually in the granular layers of the sole and scalp epidermis. Dsc 1 was strongly expressed in the superficial layer of the infundibulum and inner root sheath of the hair follicle but was not expressed in the sebaceous cells or other hair components. The eccrine duct epithelium was focally and weakly positive for Dsc 1 expression. Furthermore, Dsc 1 was not expressed in oral mucosa, although the oro-cutaneous portion was strongly expressed in the superficial layer. CONCLUSION: Dsc 1 was strongly expressed in the suprabasal cells of the epidermis during fetal skin development, and expression increased gradually in the granular layer and inner root sheath of the hair follicle. However, Dsc 1 was not expressed in basal cells or in oral mucosa. Dsc 1 may play a role in the maintenance of epithelial integrity as part of desmosomes.

Inhibitory Effect of Vitamin U (S-Methylmethionine Sulfonium Chloride) on Differentiation in 3T3-L1 Pre-adipocyte Cell Lines

BACKGROUND: S-methylmethionine sulfonium chloride was originally called vitamin U because of its inhibition of ulceration in the digestive system. Vitamin U is ubiquitously expressed in the tissues of flowering plants, and while there have been reports on its hypolipidemic effect, its precise function remains unknown. OBJECTIVE: This study was designed to evaluate the anti-obesity effect of vitamin U in 3T3-L1 pre-adipocyte cell lines. METHODS: We cultured the pre-adipocyte cell line 3T3L1 to overconfluency and then added fat differentiation-inducing media (dexamethasone, IBMX [isobutylmethylxanthine], insulin, indomethacin) and different concentrations (10, 50, 70, 90, 100 mM) of vitamin U. Then, we evaluated changes in the levels of triglycerides (TGs), glycerol-3-phosphate dehydrogenase (G3PDH), AMP-activated protein kinase (AMPK), adipocyte-specific markers (peroxisome proliferator-activated receptor gamma [PPAR-gamma], CCAAT/enhancer-binding protein alpha [C/EBP-alpha], adipocyte differentiation and determination factor 1 [ADD-1], adipsin, fatty acid synthase, lipoprotein lipase) and apoptosis-related signals (Bcl-2, Bax). RESULTS: There was a gradual decrease in the level of TGs, C/EBP-alpha, PPAR-gamma, adipsin, ADD-1 and GPDH activity with increasing concentrations of vitamin U. In contrast, we observed a significant increase in AMPK activity with increasing levels of vitamin U. The decrease in bcl-2 and increase in Bax observed with increasing concentrations of vitamin U in the media were not statistically significant. CONCLUSION: This study suggests that vitamin U inhibits adipocyte differentiation via down-regulation of adipogenic factors and up-regulation of AMPK activity.

Expression of Desmoglein-1 in Fetal Skin Development / 대한피부과학회지

BACKGROUND: Desmosomes are cell-cell adhesion complexes that provide mechanical integrity to keratinocytes by linking them to keratin intermediate filaments. Desmosomes are composed of two major transmembrane proteins, desmoglein and desmocollin. In humans, four desmoglein isoforms have been identified: Dsg1, Dsg2, Dsg3, and Dsg4. Desmogleins are Ca2+-dependent adhesion molecules and play important parts in the formation and maintenance of desmosomes. Desmoglein-1 is the main skin-associated desmosomal cadherin. It is expressed throughout the epidermis, but most prominently in the differentiated layers. OBJECTIVE: The purpose of this study was to observe the distribution pattern of desmoglein-1 in the skin and oral mucosa during fetal development. METHODS: Skin was obtained from the sole and scalp of 35 fetuses, ranging from 10 to 37 weeks of gestational age. Immunohistochemical staining was performed on paraffin embedded tissue using anti-human monoclonal antibody against desmoglein-1. RESULTS: Expression of desmoglein-1 in the epidermis appeared in the upper layer of the sole, but the basal layer was negative at the 10th gestational age. Thereafter, stratification began with stronger expression in the middle layer than in the basal layer of the sole and scalp epidermis. Expression in the middle spinous layer is stronger in the fetal period than in other layers of the epidermis. Expression in the superficial layer seemed to increase in later stages. Expression of desmoglein-1 in hair was strong in the infundibulum, inner root sheath, sebaceous glandular epithelium, and eccrine duct epithelium. Expression of desmoglein-1 in oral lip mucosa was very weak or negative in the upper half of the mucosal epithelium, though the lower half was strongly positive, while the skin side of the mucosa was similar with the sole skin. CONCLUSION: Desmoglein-1 may play a complementary role in the maintenance of epithelial integrity along with other desmogleins, because desmoglein-1 distribution is slightly different from that of desmoglein-3 in epidermis, hair and mucosa in fetal skin development.

Primary Cutaneous Mucinous Carcinoma on the Abdomen / 대한피부과학회지

Primary cutaneous mucinous carcinoma is a rare epithelial neoplasm that arises from the deepest portion of the eccrine duct. It most commonly occurs on the scalp and face with a preference for on the eyelids. The histopathologic characteristics are large mucinous pools with fibrous septae and clusters of tumor cells. We report here on a case of mucinous carcinoma that developed on the abdomen of a 47-year-old woman.

Primary Cutaneous Mucinous Carcinoma on the Abdomen / 대한피부과학회지

Primary cutaneous mucinous carcinoma is a rare epithelial neoplasm that arises from the deepest portion of the eccrine duct. It most commonly occurs on the scalp and face with a preference for on the eyelids. The histopathologic characteristics are large mucinous pools with fibrous septae and clusters of tumor cells. We report here on a case of mucinous carcinoma that developed on the abdomen of a 47-year-old woman.

A Case of Cutaneous Bronchogenic Cyst Presenting with Lymphoid Follicles

Cutaneous bronchogenic cysts are rare, and stem from developmental abnormalities of the tracheobronchial tree. The condition is often misdiagnosed clinically, with the correct diagnosis usually established by histopathologic examination. Published reports of bronchogenic or branchial anomalies are increasing, and the traditional defining characteristics of location and histopathology are proving to be less reliable for the identification of cutaneous bronchogenic cysts. In this report, we describe a case of a cutaneous bronchogenic cyst that presented with unusual histologic features, and was associated with several lymphoid follicles.

Scleromyxedema with Monoclonal Gammopathy / 대한피부과학회지

Scleromyxedema is a rare disorder characterized by generalized papular and sclerodermoid eruption, increased fibroblast proliferation, mucin deposition, and monoclonal gammopathy in the absence of thyroid disease. It is a generalized subtype of lichen myxedematosus. A paraproteinemia, typically an IgG lambda, is observed in more than 80% of patients with scleromyxedema. Here, we report a 38-year-old woman with a 1-year history of a progressively spreading of eruption of small papules on the entire body, including the face, neck, arms, legs, and trunk. Laboratory tests were within normal limits, except lambda light chain monoclonal gammopathy. We administered oral retinoid and topical steroid with slight clinical improvement. To our knowledge, this is the first reported case of scleromyxedema in Korea.

Protective effect of 4,4'-diaminodiphenylsulfone against paraquat-induced mouse lung injury

Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and transforming growth factor-beta (TGF-beta). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cmicro (PKCmicro). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.

A Case of Mycosis Fungoides Concurrent with Lymphomatoid Papulosis / 대한피부과학회지

Mycosis fungoides (MF) is the most frequent cutaneous T cell lymphoma (CTCL). Since the major tumor cell of MF is the helper T cell, positive markers are usually CD3, CD4 and CD45RO. Some MFs show CD30 positivity and the major differential diagnosis for MF with CD30 positivity includes transformed MF and MF concurrent with primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis. As each disease shows a different prognosis, an exact diagnosis is crucial for proper treatment. We now report a case of 44-year-old male patient with mycosis fungoides which developed several papules on preexisting MF patches. On biopsy of the newly formed papules, CD 30 positive cells were observed and the histologic features were consistent with lymphomatoid papulosis. Both the lesions of lymphomatoid papulosis and MF responded well to narrow band ultraviolet B phototherapy.

Lymphoepithelioma-like Carcinoma of the Upper Eyelid / 대한피부과학회지

Lymphoepithelioma-like carcinoma is a neoplasm at extranasal sites with striking histological similarity to lymphoepithelioma arising in the nasopharynx. The tumor is composed of islands of pleomorphic cells with a lymphocytic infiltrate. The head and neck are the principal locations for this tumor, which occurs in the skin. Differential diagnoses include squamous cell carcinoma, Merkel cell tumor, lymphoma, cutaneous lymphadenoma, malignant melanoma, and metastatic lymphoepithelioma. Here, we report a case of lymphoepithelioma-like carcinoma of the skin in a 78 year-old male who had a firm nodule on the right upper eyelid. He was treated with wide excision and local flap coverage. The patient had been disease-free for more than 1 year.

A Case of Lymphomatoid Keratosis

Lymphomatoid keratosis (LK) is considered to be a rare variant of cutaneous lymphoid hyperplasia, with epidermotropism. We herein report a case of LK which developed on the abdomen of an elderly Korean woman. A 60-year-old woman presented with a 10-year history of a pruritic, solitary, brown to black plaque on the abdomen. Histopathologically, the specimen showed hyperkeratosis, parakeratosis, acanthosis and Pautrier's micro-abscess in the epidermis, and a lichenoid infiltration of lymphocytes in the dermis, which expressed both B cell and T cell lineage on the immune-histochemical staining. Based on these clinical and histopathological findings, our case was diagnosed as LK. To our knowledge, this is the first case report of LK in the Korean dermatologic literature.

Differential alternative splicing of human transglutaminase 4 in benign prostate hyperplasia and prostate cancer

Transglutaminase 4 is a member of enzyme family that catalyzes calcium-dependent posttranslational modification of proteins. Although transglutaminase 4 has been shown to have prostate-restricted expression pattern, little is known about the biological function of transglutaminase 4 in human. To gain insight into its role in prostate, we analyzed the expression status of human transglutaminase 4 in benign prostate hyperplasia (BPH) and prostate cancer (PCa). Unexpectedly, RT-PCR and nucleotide sequence analysis showed four alternative splicing variants of transglutaminase 4: transglutaminase 4-L, -M (-M1 and -M2) and -S. The difference between transglutaminase 4-M1 and -M2 is attributed to splicing sites, but not nucleotide size. The deduced amino acid sequences showed that transglutaminase 4-L, -M1 and -M2 have correct open reading frames, whereas transglutaminase 4-S has a truncated reading frame. RT-PCR analysis of clinical samples revealed that transglutaminase 4-M and -S were detected in all tested prostate tissue (80 BPH and 48 PCa). Interestingly, transglutaminase 4-L was found in 56% of BPH (45 out of 80) and only in 15% of PCa (7 out of 48). However, transglutaminase 4-L expression did not correlate with serum prostate-specific antigen (PSA) level, prostate volumes or PSA densities. These results will provide a clue to future investigation aiming at delineating physiological and pathological roles of human transglutaminase 4.

Langerhans Cell Histiocytosis That Improved with Oral Isotretinoin Therapy / 대한피부과학회지

Langerhans cell histiocytosis (LCH) is a reactive disease in which abnormal Langerhans cells accumulate in various body sites. We report here on a 51-year-old male patient with LCH that was classified as single-system disease (restricted LCH). The skin lesions were a small, deep ulcer in the right inguinal area and multiple erythematous papules scattered on the lower abdomen, and the patient had these lesions for 1 year. The histopathologic examination revealed a dense histiocytic infiltration in the dermis, and most of the cells showed the characteristics of "LCH" cells. The immunohistochemistry for S-100 protein and CD1a complex all showed positive results. The patient was much improved after surgical excision of the inguinal ulcer and administering oral isotretinoin (20 mg daily) for 8 months, and there was no recurrence. We think retinoid is an effective treatment option for LCH, especially for single system disease.