Associations between genetic polymorphisms of membrane transporter genes and prognosis after chemotherapy: meta-analysis and finding from Seoul Breast Cancer Study (SEBCS).

Membrane transporters can be major determinants of the pharmacokinetic profiles of anticancer drugs. The associations between genetic variations of ATP-binding cassette (ABC) and solute carrier (SLC) genes and cancer survival were investigated through a meta-analysis and an association study in the Seoul Breast Cancer Study (SEBCS). Including the SEBCS, the meta-analysis was conducted among 38 studies of genetic variations of transporters on various cancer survivors. The population of SEBCS consisted of 1338 breast cancer patients who had been treated with adjuvant chemotherapy. A total of 7750 SNPs were selected from 453 ABC and/or SLC genes typed by an Affymetrix 6.0 chip. ABCB1 rs1045642 was associated with poor progression-free survival in a meta-analysis (HR = 1.33, 95% CI: 1.07-1.64). ABCB1, SLC8A1, and SLC12A8 were associated with breast cancer survival in SEBCS (Pgene < 0.05). ABCB1 rs1202172 was differentially associated with survival depending on the chemotherapy (Pinteraction = 0.035). Our finding provides suggestive associations of membrane transporters on cancer survival.

Melanogenesis inhibition of ß-lapachone, a natural product from Tabebuia avellanedae, with effective in vivo lightening potency.

ß-Lapachone is an ortho naphthoquinone obtained from the bark of the lapacho tree (Tabebuia avellanedae), which has been used medicinally for centuries. The purpose of this study was to investigate the effects of ß-lapachone on inhibitory mechanism of melanogenesis. ß-Lapachone inhibited melanin synthesis and tyrosinase activity at 0.8 µM in melan-a cells. Also, ß-lapachone reduced the expression of tyrosinase and tyrosinase-related protein-1 at transcriptional and translational levels. The decreased expression of tyrosinase and tyrosinase-related protein-1 might result from the reduced microphthalmia-associated transcription factor (MITF) level which regulates major melanogenic proteins. The reduced level of MITF was associated with delayed ERK activation by ß-lapachone. Furthermore, ß-lapachone reduced melanogenesis in the human 3D skin tissue culture; besides, it dramatically inhibited body pigmentation of zebrafish and decreased melanin content and tyrosinase activity. These results show that ß-lapachone may be useful as a potential depigmentation agent for various hyperpigmentation disorders.

Diversity of rotavirus strain circulated in gwangju, republic of Korea.

OBJECTIVES: The introduction of new rotavirus vaccines into the public sphere makes it necessary to maintain constant surveillance and to heighten public awareness of the appearance of new rotavirus strains. We describe the molecular epidemiology of circulating rotavirus strains after vaccine introduction. METHODS: We collected a total of 1070 stool samples from children with gastroenteritis from January 2013 to June 2013. The antigenic prevalence of rotavirus group A was distinguished using enzyme immunoassay. The G and P genotypes of enzyme immunoassay-positive samples were determined with reverse transcription-polymerase chain reaction and nucleotide sequencing analysis. RESULTS: Of the 1070 samples collected, 277 (25.9%) tested positive for rotaviruses by enzyme-linked immunoabsorbent assay. The most prevalent circulating genotype G was G1 (51.3%), followed by G2 (34.7%) and G9 (10.8%). The predominant type of genotype P was P[8] (66.1%), followed by P[4] (31.4%). In this study, nine genotypes were found. G1P[8] was the most prevalent (51.8%), followed by G2P[4] (30.5%), G9P[8] (9.9%), and G2P[8] (4.0%). Several unusual combinations (G1P[4], G3P[9], G3P[8], G4P[6], and G9P[4]) were also identified. CONCLUSION: Molecular epidemiological knowledge of rotaviruses is critical for the development of effective preventive measures, including vaccines. These data will help us monitor the effectiveness of current rotavirus vaccines.

Impact on inflammation and recovery of skin barrier by nordihydroguaiaretic Acid as a protease-activated receptor 2 antagonist.

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-NH2. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular Ca(2+) in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.