Cytotoxic ergosterols from Paecilomyces sp. J300

Seven ergosterol derivatives (1-7) were isolated from silkworm larvae infected with Paecilomyces sp. J300. On the basis of spectroscopic means, their structures have been elucidated as 3beta,5alpha-dihydroxy-ergosta-7,22-diene (1), 5alpha,6alpha-epoxy-(22E,24R)-ergosta-8(14), 22-diene-3beta, 7alpha-diol (2), 5alpha,6alpha-epoxy-(22E,24R)-ergosta-8,22-diene-3beta,7alpha-diol (3), ergosta-4,6,8(14),22-tetraene-3-one (4), ergosterol (5), ergosterol endoperoxide (6), 3beta,5alpha-dihydroxy-6beta-methoxyergosta-7,22-diene (7). Compounds 3-7 showed moderate cytotoxicity against five tumor cells.     

Review of pharmacoeconomic evaluation of genotype-guided antiplatelet therapy

Introduction: Clopidogrel is an antiplatelet agent widely prescribed for acute coronary syndrome (ACS), and it is activated by the CYP enzyme system to active metabolite. CYP2C19 loss-of-function (LOF) allele(s) affect the responsiveness of clopidogrel, but not the new antiplatelet agents (prasugrel and ticagrelor). We reviewed the pharmacoeconomic studies on genotype-guided use of new antiplatelet agents.

Areas covered: A literature search was conducted between the period of 2000 and 2014. Seven studies including cost-effectiveness and risk-benefit analyses of CYP2C19 genotype-guided antiplatelet therapy in ACS patients were reviewed. Genotype-guided prasugrel was found to be cost-effective when compared with universal antiplatelet therapy in four studies. Three studies showed genotype-guided ticagrelor to be cost-effective in ACS patients with percutaneous coronary intervention (PCI), and universal ticagrelor to be cost-effective in ACS patients. Drug cost of antiplatelet agents and relative risk of the new antiplatelet versus clopidogrel for clinical events were common influential factors of cost-effectiveness analyses.

Expert opinion: All studies in the present review focused on selecting antiplatelet agents for carriers of CYP2C19 LOF allele(s). Cost-effectiveness of genotype-guided use of antiplatelets was demonstrated in high-risk ACS patients.     

Combined Skin Moisturization of Liposomal Serine Incorporated in Hydrogels Prepared with Carbopol ETD 2020, Rhesperse RM 100 and Hyaluronic Acid

We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water-in-oil (W/O) cream); their moisturizing abilities were then assessed using a Corneometer®. The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products.     

Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their Whitening Activities

The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects against melanogenesis and tyrosinase activities. By bioassay-guided isolation, ten phenolic compounds were isolated by column chromatography from SPEE. The whitening effect of the isolated compounds from SPEE were tested for the inhibitory activities against melanogenesis using B16 melanoma cells, in vitro inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA) auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid and quercetin revealed significant inhibitory activities against melanogenesis compared to arbutin. In particular, quercetin exhibited similar inhibitory activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These results suggested that SPE could be used as a potential source of natural skin-whitening material in cosmetics as well as in food products.     

Breast cancer subtypes and survival in patients with brain metastases

Introduction

Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated.

Methods

Retrospective survival analyses were performed in 126 BM patients from 805 MBC patients treated at the National Cancer Center between August 2001 and April 2006, according to clinical characteristics, breast cancer subtypes, and receipt of trastuzumab. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were tested by immunohistochemical (IHC) staining, and HER2 FISH analysis conducted for IHC 2+.

Results

The proportion of HER2+/ER- (29% vs 16%) and triple-negative (37% vs 25%) tumors was higher in the 126 BM patients than those without BM. While median survival after recurrence was longer in patients with luminal A disease (median survival of luminal A vs luminal B vs HER2+/ER- vs triple-negative: p = 0.0246; 39.6 vs 27.4 vs 20.9 vs 15.5 months), survival was shorter from BM to death in luminal A and triple negatives (median survival: p = 0.0113; 4.0 vs 9.2 vs 5.0 vs 3.4 months). Receipt of trastuzumab after BM was a significant variable for survival in HER2+ patients. Multivariate analyses identified ER-negative, HER2-negative, or triple-negative, as well as older age, presence of leptomeningeal disease, and three or more extracranial disease sites, as poor prognostic factors for survival after BM.

Conclusion

MBC patients who developed BM had higher proportions of triple-negative and HER2+/ER- tumor status. Triple receptor status is a useful prognostic marker for predicting survival after BM in metastatic breast cancer patients.     

Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with germline mutations in the VHL gene. VHL disease, as well as several other cancer syndromes, has been associated with an increased risk of pheochromocytomas, which are catecholamine-secreting tumors of the adrenal gland. VHL disease genotype-phenotype correlations have been well established based on the type of mutations in the VHL gene. However, although many groups have reported VHL germline mutations in different countries, no previous report has described VHL gene mutations in VHL disease and/or pheochromocytoma patients in Korea. In this study, we used direct sequencing to investigate VHL germline mutations in Korean patients with VHL disease or pheochromocytomas (11 VHL patients and 3 additional members from 7 families, 2 patients from 1 family with familial pheochromocytoma, and 2 cases of isolated pheochromocytoma). We found a total of 7 VHL germline mutations (6 missense and 1 frameshift), 3 of which were novel (323_324delGC, 355T>C and 361G>A). No VHL germline mutation was found in the 2 patients with isolated pheochromocytomas and paragangliomas. This study provides informative data for VHL germline mutations and VHL-related phenotypes in Korea.     

Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer

Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2′-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression. The same AREG gene-body methylation was also found in human colorectal cancer samples and is independent of KRAS and NRAS mutations. Methylation is specifically decreased in the tumor epithelial compartment as compared to stromal tissue and normal epithelium. Investigation of a promoter/enhancer function of the AREG exon 2 region revealed a potential promoter function in reverse orientation. Retrospective comparison of the predictive power of AREG gene-body methylation versus AREG gene expression using samples from colorectal cancer patients treated with anti-EGFR inhibitors with complete clinical follow-up revealed that AREG expression is superior to AREG gene methylation. AREG and EREG genes undergo a complex regulation involving both intragenic methylation and promoter-dependent control.     

Outer photoreceptor layer thickness mapping in normal eyes and eyes with various macular diseases using spectral domain optical coherence tomography: A pilot study

Background

To obtain a de novo map of outer photoreceptor layer (OPRL) thickness using a semiautomatic segmentation method for commercial spectral-domain optical coherence tomography (SD-OCT) and analyze the features of the resulting OPRL map in normal eyes and eyes with various inactive macular diseases.

Methods

Forty normal eyes and 50 eyes with various inactive macular diseases such as resolved central serous chorioretinopathy (20 eyes), surgically-repaired macular hole (10 eyes), epiretinal membrane (10 eyes), and reattached rhegmatogenous retinal detachment (10 eyes) were screened. All subjects underwent a 12 radial scan protocol in SD-OCT. The segmentation lines defining the OPRL were modified using built-in software. The diseased eyes were subdivided into two groups (good vision, or intermediate to poor vision) based on a visual acuity better or worse than 20/40. The map of the OPRL thickness was obtained automatically by the embedded software and was presented as the Early Treatment Diabetic Retinopathy Study (ETDRS) style.

Results

The mean OPRL thickness in normal eyes in all subfields was 40.37?±?4.35 μm. The central subfield area showed the greatest mean OPRL thickness in normal eyes. The mean OPRL thickness of diseased eyes with good vision in the central subfield was greater than that of eyes with intermediate to poor vision. The OPRL thickness map showed various patterns according to the type of macular diseases.

Conclusions

We suggest that our semiautomated segmentation method using a 12 radial scan protocol is simple, fast, and suitable for producing a reliable OPRL map with ETDRS. This quantitative data could be useful in clinical practice or research of various macular diseases.     

果糖二磷酸钠对动物急性脑缺血的保护作用

目的：研究口服果糖二磷酸钠（ＦＤＰ）对动物缺氧及急性脑缺血的保护作用。方法：采用常压密闭、断头、结扎双侧带迷走神经颈总脉态等方法,观察ＦＤＰ对缺氧及急性脑缺血小鼠死亡时间的影响;采用结扎双侧颈总动脉的方法,观察ＤＦＰ对急性脑缺血大鼠的影响。结果：ＤＦＰ可明显延长常压密闭、断头、结扎双侧带迷走神经颈总动脉后小鼠的死亡时间,可明显降低结扎双侧颈总动脉造成的大鼠脑指数、脑含水量和血清磷酸肌酸激酶的增高,