[Show abstract][Hide abstract] ABSTRACT: Glioblastoma (GBM) heterogeneity in the genomic and phenotypic properties has potentiated personalized approach against specific therapeutic targets of each GBM patient. The Cancer Genome Atlas (TCGA) Research Network has been established the comprehensive genomic abnormalities of GBM, which sub-classified GBMs into 4 different molecular subtypes. The molecular subtypes could be utilized to develop personalized treatment strategy for each subtype. We applied a classifying method, NTP (Nearest Template Prediction) method to determine molecular subtype of each GBM patient and corresponding orthotopic xenograft animal model. The models were derived from GBM cells dissociated from patient's surgical sample. Specific drug candidates for each subtype were selected using an integrated pharmacological network database (PharmDB), which link drugs with subtype specific genes. Treatment effects of the drug candidates were determined by in vitro limiting dilution assay using patient-derived GBM cells primarily cultured from orthotopic xenograft tumors. The consistent identification of molecular subtype by the NTP method was validated using TCGA database. When subtypes were determined by the NTP method, orthotopic xenograft animal models faithfully maintained the molecular subtypes of parental tumors. Subtype specific drugs not only showed significant inhibition effects on the in vitro clonogenicity of patient-derived GBM cells but also synergistically reversed temozolomide resistance of MGMT-unmethylated patient-derived GBM cells. However, inhibitory effects on the clonogenicity were not totally subtype-specific. Personalized treatment approach based on genetic characteristics of each GBM could make better treatment outcomes of GBMs, although more sophisticated classifying techniques and subtype specific drugs need to be further elucidated.
PLoS ONE 08/2014; 9(8):e103327. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma multiforme (GBM), the most common and aggressive malignant brain tumor, almost always recurs despite aggressive treatments combining surgery, radiation, and chemotherapy. Thus, understanding how individual tumors evolve in response to the standard treatments is essential for improved patient care.
[Show abstract][Hide abstract] ABSTRACT: Hardening phenomenon of human skin after repeated exposure to the irritants is well-known, but the precise mechanism remains elusive.
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.
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.
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.
Repetitive stimulation with a higher concentration of SLS can more easily trigger skin hardening.
Annals of Dermatology 02/2014; 26(1):35-42. · 0.95 Impact Factor
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[Show abstract][Hide abstract] ABSTRACT: Due to innate high metastatic ability of renal cell carcinoma (RCC), many patients with RCC experience local or systemic relapses after surgical resection. A deeper understanding of the molecular pathogenesis underlying advanced RCC is essential for novel innovative therapeutics. Tumor Progression Locus 2 (Tpl2), upregulated in various tumor types, has been reported to be associated with oncogenesis and metastatic progression via activation of mitogen activated protein kinase (MAPK) pathways. Herein we aim to explore the relevance of Tpl2 in tumor growth and metastasis of RCC. Inspection of The Cancer Genome Atlas database indicated that Tpl2 overexpression was significantly related to presence of metastases and worse outcomes of clear cell RCC (ccRCC), which is the most aggressive subtype of RCC. Moreover, expression of Tpl2 and Chemokine Receptor type 4 (CXCR4) showed positive correlation. Depletion of Tpl2 activity with short hairpin (sh) RNAs or a Tpl2 kinase inhibitor in human ccRCC cells including Caki-1 remarkably suppressed MAPK pathways and impaired in vitro cell proliferation, clonogenicity, anoikis resistance, migration, and invasion capabilities. Consistent with the in vitro data, orthotopic xenograft growth and lung metastasis of Caki-1 cells were significantly inhibited by Tpl2 silencing. Furthermore, Tpl2 knockdown in Caki-1 cells reduced chemokine (C-X-C motif) ligand 12 (CXCL12) directed chemotaxis/chemoinvasion accompanied with impaired downstream signaling, indicating potential involvement of Tpl2 in CXCR4 mediated metastasis. Taken together, these data suggest that Tpl2 can be a novel potential therapeutic target linked to the disease progression of ccRCC.
Molecular Cancer Research 08/2013; · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
Plasma histamine concentrations and DAO activities were evaluated to determine whether there are abnormalities in the histamine metabolism of CIU patients.
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.
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.
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.
Annals of Dermatology 05/2013; 25(2):189-195. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
To examine the prevalence and status of food hypersensitivity among childhood AD patients in Korea.
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.
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.
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.
Annals of Dermatology 05/2013; 25(2):196-202. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fractional technology overcomes the problems of ablative lasers, such as inaccurate depth control and damage to the epidermis. Minimally invasive fractional radiofrequency microneedle devices allow for more-selective heating of the dermis.
To evaluate the clinical efficacy of fractional radiofrequency microneedle (ERM) treatment in acne scars and large facial pores.
Thirty patients with acne scars and large facial pores were enrolled. Bipolar radiofrequency energy was delivered to the skin through the electrodes of the FRM device. Skin lesions were evaluated according to grade of acne scars, Investigator Global Assessment of large pores, skin surface roughness, transepidermal water loss (TEWL), dermal density, microscopic and composite image, sebum measurement, and questionnaires regarding patient satisfaction.
The grade of acne scars and Investigator Global Assessment of large pores improved in more than 70% of all patients. Skin surface roughness, dermal density, and microscopic and composite images also improved, whereas TEWL and sebum measurement did not change.
Clinical improvement from FRM treatment appeared to be related to dermal matrix regeneration. FRM treatment may be effective in improving acne scars and facial pores.
Dermatologic Surgery 04/2012; 38(7 Pt 1):1017-24. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: People with sensitive skin (SS) are those who state their skin is more sensitive than that of average persons. The stratum corneum is responsible for maintaining skin barrier function. Ceramides, major constituents of stratum corneum lipids, have been shown to predominantly contribute to the role. It has been suggested that barrier function in SS is decreased. However, we could find very few reports about stratum corneum ceramides in SS. This study was done to find out differences in stratum corneum ceramides between SS and non-SS groups. Fifty individuals (20 with SS and 30 with non-SS) were recruited. Lactic acid sting test (LAST) was performed on the left cheek. On six sites including the right cheek, arm, thigh, leg, back and palm, transepidermal water loss (TEWL) and erythema index (EI) were measured. On the above six sites, stratum corneum sheets were obtained by stripping with cyanoacrylate resin and stratum corneum lipids were extracted, then, analyzed by high-performance liquid chromatography electrospray ionization mass spectrometry. LAST scores were higher in the SS group, but not statistically significant. There were no differences in TEWL and EI values between the two groups. The mean value of the quantity of stratum corneum ceramides on the face was significantly lower in the SS group. On other sites, mean values were also lower in the SS group, but not statistically significant. The quantity of ceramides was significantly decreased in the face of the SS group compared to that of the non-SS group. These results suggest that the decrease in stratum corneum ceramides on facial skin could be related to SS development.
The Journal of Dermatology 03/2012; 39(3):295-300. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although much research has been conducted into the origin of syringoma, the histogenesis and differentiation of it remains controversial. The published studies examined various antibodies, and our study is an additional immunohistochemical work-up.
We attempted to identify the cell that acts as the precise origin of a syringoma, based on a comparative analysis of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratin (CK) 5 through immunohistochemical staining in the solid strand of basophilic epithelial cells of syringoma.
A total of 31 patients with biopsy-confirmed syringoma were included in this study. Each sample was analyzed with antibodies to CEA, EMA, and CK5. These markers were indicating each part of the normal sweat gland structure: CEA stains the luminal surface of sweat ductal structures; EMA stains the peripheral cells of normal dermal ducts and the intraepidermal duct; CK5 stains the outer cells of the dermal duct and lower intraepidermal duct but does not stain the intraepidermal duct located in the upper epidermis.
We were able to confirm that the solid strands stained for EMA and CK5, as did the outer cells of the ductal structure. However, the solid strands did not stain with CEA.
The results indicated that solid strands observed in syringomas originate from the outer cells of the two layers of cells that compose the lower epidermal duct or the transitional portion between the intraepidermal duct and dermal duct in the normal eccrine or apocrine structure. Thus, we surmise that a syringoma is developed by the proliferation of these cells.
International journal of dermatology 11/2011; 51(7):817-22. · 1.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A cutaneous metaplastic synovial cyst (CMSC) is a cyst lined with metaplastic synovial tissue, which includes the formation of an intracystic villous structure resembling hyperplastic synovial villi. Clinically, the lesion is a tender, subcutaneous nodule that usually occurs at the site of previous surgical trauma and is frequently misdiagnosed as a suture granuloma. The actual cause remains unclear; however, trauma is presumed to be a precipitating factor, as most reported cases have demonstrated a history of antecedent cutaneous injury. Here, we present a case of CMSC in a 51-year-old woman who presented with a cystic mass localized in the left sole. She had no history of previous trauma or surgical procedures performed in the area. Although the case explained in this report is a spontaneous case of CMSC that occurred without a history of trauma, it is believed to have been caused by constant and chronic pressure since CMSC occurred in the first metatarsal head area, a part of the sole where heavy pressure is consistently applied.
Annals of Dermatology 10/2011; 23(Suppl 2):S165-8. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign cephalic histiocytosis (BCH) is a rare non-Langerhans cell histiocytosis of unknown etiology. Clinically, lesions are characterized by small, red-to-yellow papules distributed mainly on the head, face, neck, and shoulders of infants and children. Histopathological specimens show massive histiocytic infiltration of the superficial dermis. Immunohistochemically, they are positive for CD68, but negative for CD1a and S-100. Two cases have been reported so far in the relevant work published in Korean literature. Herein, we report on an additional case of BCH.
[Show abstract][Hide abstract] ABSTRACT: This report presents a case of nodular colloid degeneration in a 76-year-old man with a solitary facial lesion. The skin lesion was a yellowish indurated plaque on the left mandibular area. Histopathologic examination revealed the amorphous colloid material in the upper dermis. The Congo red stain was negative, no birefringence was observed under polarized light, and elastic stain showed positivity in both the colloid and the surrounding fibers. To the best of our knowledge, nodular colloid degeneration is a rare entity and has only been reported in published literature a few times in the last 8 decades.
The American Journal of dermatopathology 10/2010; 33(4):388-91. · 1.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psoriasis is a chronic skin disease that appears to be autoimmune in nature. Recently, it is thought that microbial pathogens of skin can affect the pathogenesis of psoriasis by inducing autoimmunity. Heat-shock proteins (HSPs) are known to play an important role in immune and inflammatory responses of the skin including psoriasis. Recent studies have suggested that Toll-like receptors (TLR) 2, 4 and gammadelta T-cell receptors (TCR-gammadelta) may recognize HSP60 as a ligand and consequently activate the immune system.
The biopsy specimens of 12 of guttate psoriasis, 12 of plaque psoriasis and five of normal skin were studied using immunohistochemical staining. The expressions of HSP60, TLR2 and TLR4 were evaluated using an immunostaining-intensity-distribution (IID) index and TCR-gammadelta positive cells were counted.
The expression of HSP60 was significantly higher in guttate and plaque psoriasis than in normal skin. The expression of TLR4 was higher in guttate psoriasis than in plaque psoriasis and normal skin. The expression of TCR-gammadelta was higher in guttate and plaque psoriasis than in normal skin, but there was no correlation found between the expression of HSP60 and TLRs 2 and 4, or between that of HSP60 and TCR-gammadelta.
HSP60 may be related to the pathogenesis of both guttate and plaque psoriasis and TLR4 may be related to the pathogenesis of guttate psoriasis.
Journal of Cutaneous Pathology 01/2008; 34(12):903-11. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was aimed to alert the hazard of accidental adverse reactions of photochemotherapy (Psoralen-UVA or PUVA) that has been used in the treatment for some skin diseases and commercially for cosmetic tanning. Aside from the predictable side effects of PUVA such as erythema and itching, the accidental adverse reactions such as extensive burns could occasionally occur. Our observations indicated that six cases resulted from mistakes of medical personnel, and six other cases resulted from unsupervised mistakes of patients. The conditions that needed photochemotherapy were seven cases of vitiligo, three cases of psoriasis and two cases of tanning. The accidental overdose of UV radiation was about 3-10 times the empirically normal dose. Five of our patients were supposed to undergo topical PUVA, but they were irradiated at the dose of oral PUVA. One patient applied 8-methoxypsoralen (8-MOP) cream together with taking 5-methoxypsoralen (5-MOP) tablets for oral PUVA. Three other patients enjoyed sunbathing 1-3h shortly after finishing PUVA. A young couple chose 5-MOP to enhance tanning and sunbathed about 1h later. When another patient resumed PUVA in a 6-month cessation, he was exposed at a previous dose instead of a starting dose. Erythema and blisters of second degree burns developed in all our cases, 36-72h after PUVA, with 5-25% of body surface involved. Among the 12 patients, 3 were admitted and 9 were treated on an outpatient basis. All patients recovered in 1-3 weeks with no skin graft or no significant sequelae except post-inflammatory hyperpigmentation.
[Show abstract][Hide abstract] ABSTRACT: Using 1H-MRS, we evaluated the effects of growth hormone (GH) as a caspase inhibitor on hypoxic-ischemic injury in neonatal rat brains. The right common carotid arteries of rats were ligated, allowed to recover for 3 hr, and exposed to 8% oxygen for 2 hr. GH was given just prior to HI insult and animals were divided into four groups: control, intracerebroventricular (ICV), intracerebroventricular/intraperitoneal (ICV/IP), and intraperitoneal (IP). Localized in vivo 1H-MRS and TUNEL staining were performed 24 hr after HI injury. Lipid/N-acetyl aspartate (NAA) and lipid/creatine (Cr) ratios were used as apoptotic markers. Gross morphologic changes at 2 weeks were used to evaluate the effects of GH. The lipid/NAA ratio was lower in the ICV and ICV/IP groups than in the control, and the lipid/Cr ratio was lower in the ICV group than in the control. The number of TUNEL positive cells was decreased in the ICV and ICV/IP groups, and the degree of morphologic change indicative of brain injury was lower in the ICV group and somewhat lower in the ICV/IP group. The degree of morphologic change correlated with the lipid/NAA and lipid/Cr ratios. These findings suggest that GH exerts neuroprotective effects in cerebral hypoxic-ischemic injury.
Journal of Korean Medical Science 03/2007; 22(1):122-6. · 1.25 Impact Factor