Analysis of microsatellite instability in Korean patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a dangerous malignancy with a high mortality rate. Diagnosing PC at an early stage is difficult, and approximately 5% of the patients survive for 5 years. Microsatellite instability (MSI) plays an important role in colorectal cancer (CRC) for prognosis and immunotherapy. Evaluation of MSI status is important as it is recognized biomarker for the positive response of immune checkpoint blockade therapy in cancer. To our knowledge, there is no report yet on the prevalence of MSI in Korean PC patients. Studies have reported conflicting prevalence of MSI in PC. METHODS: Therefore, to improve the likelihood of MSI identification in PC, we included 133 patients with PC; paired tumor and normal tissue DNA were isolated and MSI was analyzed using Promega panel and immunohistochemistry (IHC) was also performed. RESULTS: Our results from the Promega panel indicated that one (0.7%) tumor was MSI-high (MSI-H), 13 (9.8%) were MSI-low (MSI-L), and 119 (89.5%) were microsatellite stable (MSS). IHC result also confirmed dMMR in only one sample. CONCLUSIONS: The finding of low incidence of MSI-H observed by the Promega panel also matched IHC results, so this study suggested that in Korean PC patients, MSI prevalence is infrequent.

Insulin-Like Growth Factor-1 Increases the Expression of Inflammatory Biomarkers and Sebum Production in Cultured Sebocytes.

BACKGROUND: Acne vulgaris has been linked to the Western diet. Hyperglycemic diet increases insulin and insulin-like growth factor (IGF)-1. Deeper insights into IGF-1-mediated signal pathway are critical importance to understand the impact of Western diet. OBJECTIVE: We investigated the effect of IGF-1 on the expression of inflammatory biomarkers and sebum production in cultured sebocytes. METHODS: Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure changes in the expression of inflammatory biomarkers including interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), IGF1R, IGFBP2, sterol response element-binding protein (SREBP), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) after the treatment of cultured sebocytes with 10-7 M or 10-5 M IGF-1. Sebum production was evaluated after the treatment of cultured sebocytes with 10-7 M or 10-5 M IGF-1 using lipid analysis. RESULTS: The expression levels of IL-1ß, IL-6, IL-8, and TNF-α in cultured sebocytes after treatment with 10-7 M or 10-5 M IGF-1 were increased. Increased gene expression levels of NF-κB in cultured sebocytes were also shown after 10-7 M or 10-5 M IGF-1 treatments. Gene expression of these inflammatory biomarkers was decreased after 10-7 M or 10-5 M IGF-1 treatment in the presence of 100 nM NF-κB inhibitor. Treatment with 10-7 M or 10-5 M IGF-1 increased the gene expression levels of IGF1R, IGFBP2, SREBP and PI3KCA in cultured sebocytes. Sebum production from cultured sebocytes treated with 10-7 M or 10-5 M IGF-1 was also increased. CONCLUSION: It is suggestive that IGF-1 might be involved in the pathogenesis of acne by increasing both expression of inflammatory biomarkers and also sebum production in sebocytes.

Ultraviolet B irradiation increases the expression of inflammatory cytokines in cultured sebocytes.

Sebaceous gland hyperplasia and increased sebum secretion after irradiation of ultraviolet (UV)-B has been widely accepted. This study was performed to clarify expression of inflammatory cytokines after irradiating UV-B in cultured sebocytes. Reverse transcription polymerase chain reaction was performed to measure gene expression of inflammatory cytokines, including interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α, in cultured sebocytes after exposure to 40 and 70 mJ/cm(2) UV-B. Protein expression of inflammatory cytokines and lipid production in cultured sebocytes after exposure to UV-B were measured using enzyme-linked immunoassay and lipid analysis kit. The expression of inflammatory cytokines, especially IL-1ß and IL-8, was significantly increased in cultured sebocytes after treatment with UV-B. Many more studies on the effect of UV-B on sebaceous glands should be performed to reveal the pathogenic mechanism of acne.

Expression of Inflammatory Biomarkers from Cultured Sebocytes was Influenced by Treatment with Vitamin D.

BACKGROUND: Inflammatory cytokines are the key factor in the pathophysiology of acne. It is well known that keratinocytes synthesize many kinds of inflammatory cytokines. In addition, it is reported that inflammatory cytokines are also expressed from sebocytes, which originate from the same stem cells with keratinocytes. AIM: To clarify changes in the expression of inflammatory biomarkers from cultured sebocytes after treatment with vitamin D. MATERIALS AND METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was done to measure changes in the expression of inflammatory biomarkers, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor-α (TNF-α), and several subtypes of matrix metalloproteinases (MMPs) after treatment of a group of cultured sebocytes with vitamin D. Vitamin D receptor (VDR) small interfering RNA (siRNA) was added in the other group of cultured sebocytes to assure the role of vitamin D on the expression of inflammatory biomarkers. Enzyme-linked immunosorbent assay (ELISA) was also performed in the vitamin D-treated sebocytes. RESULTS: Cultured sebocytes showed non-significant changes in the gene expression of inflammatory biomarkers after treatment with vitamin D. In cultured sebocytes treated with a VDR siRNA, the expression of inflammatory biomarkers was not blocked after treatment with vitamin D. ELISA showed a significant decrease in the expression of IL-6, IL-8, and MMP-9, but a significant increase in the expression of MMP-1 and MMP-3, after treatment with vitamin D (10(-6) M). CONCLUSION: Expression of inflammatory biomarkers is influenced by treatment with vitamin D in cultured sebocytes, but not through VDR.

Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and Down-regulate Their TLR-2 and TLR-4 Expression.

BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS: There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.

Ear keloids as a primary candidate for the application of mitomycin C after shave excision: in vivo and in vitro study.

BACKGROUND: Although many methods have been developed to treat ear keloids, new therapeutic options are still needed. OBJECTIVE: To determine the effects of topical mitomycin C (MC) on shave-removed wounds and fibroblasts of ear keloids. METHODS: Fourteen ear keloids in 12 patients were shaved, and MC (1 mg/mL) was applied to the resected bed for 5 minutes. The application was repeated 3 weeks later. All patients were assessed 2, 4, and 6 months after the procedure to evaluate the cosmetic results, recurrence, and postsurgical complications. An in vitro study to determine the effects of MC on fibroblasts of the excised keloids was conducted using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the measurement of total cell counts, and immunoassay of DNA synthesis. RESULTS: Only one recurrence occurred (on the ear helix), and the patients were satisfied with the cosmetic outcomes. The results of the MTT assay, total cell counts, and DNA synthesis immunoassay confirmed the suppressive effects of MC on the keloid fibroblasts. CONCLUSION: The application of topical MC to the resected bed of shave-removed ear keloids was successful in preventing recurrences and providing an acceptable cosmetic outcome.