Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers.

Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were administered a single dose of gefitinib and the blood samples were used for quantifying the concentration of gefitinib and genotyping fifteen single-nucleotide polymorphisms of cytochrome P450 enzymes (CYP3A4, CYP3A5, CYP2D6, CYP2C9 and CYP2C19) and drug transporters (ABCB1 and ABCG2).CYP3A5*3 (rs776746) polymorphism showed a significant influence, with higher gefitinib AUC0-t in carrier of CC genotype than in CT/TT genotype (BH-adjusted p value <0.05). For CYP2C9*3 (rs1057910), significant differences in pharmacokinetics of gefitinib were detected between carriers of AA and AC genotypes, with higher AUC0-t, AUC0-∞ and Cmax in carrier of AC genotype than in AA gen-otype (BH-adjusted p value <0.05). No associations were found between SNPs in CYP3A4, CYP2D6, CYP2C19, ABCB1, ABCG2 and the pharmacokinetics of gefitinib.The SNPs in CYP3A5*3 (rs776746) and CYP2C9*3 (rs1057910) were found to be associated with altered gefitinib pharmacokinetics in healthy Chinese volunteers.

Tail regeneration after autotomy revives survival: a case from a long-term monitored lizard population under avian predation.

Caudal autotomy in lizards has intrigued scientists for more than 100 years. Because of the relative lack of literature under natural conditions, the complicated association among field autotomy rate, real predation pressure, the long-term cost of tail loss, and the benefit of regeneration remains equivocal. In this study, we conducted a 7-year capture-mark-recapture (CMR) programme with a wild population of a sexually dichromatic lizard, Takydromus viridipunctatus We used autotomy indexes and a contemporary bird census mega-dataset of four predatory birds as predictors to examine the association between tail loss and predation pressure. We further estimated the survival cost of tail loss and alleviation by regeneration under natural conditions through CMR modelling. We found that large and small avian predators affect lizard survival through the following two routes: the larger-sized cattle egret causes direct mortality while the smaller shrikes and kestrels are the major causes of autotomy. Following autotomy, the survival rate of tailless individuals over the next month was significantly lower than that of tailed individuals, especially males during the breeding season, which showed a decline of greater than 30%. This sex-related difference further demonstrated the importance of reproductive costs for males in this sexually dichromatic species. However, the risk of mortality returned to baseline after the tails were fully grown. This study indicates the benefit of tail regeneration under natural conditions, which increases our understanding of the cost-benefit dynamics of caudal autotomy and further explains the maintenance of this trait as an evolutionarily beneficial adaption to long-term predator-prey interactions.

Strict consistency between genetic and topographic landscapes of the brown tree frog (Buergeria robusta) in Taiwan.

Taiwan presents an excellent opportunity to build a phylogeographic paradigm for fine-scaled differentiation occurring within short distances on an single island. Due to the limitation of habitat availability on the island, demographic histories of species in Taiwan were strongly influenced by glacial-interglacial cycles. Nevertheless, there are relatively few studies demonstrating such phylogeographic patterns for islands, especially in subtropical Asia. In this study, we aim to construct the genetic landscape of a philopatric stream frog Buergeria robusta by an intense and fine-scaled collection throughout the island. The deduced genetic landscape of B. robusta presented extremely high congruence with the actual topography of Taiwan. Two major lineages were found on the eastern and the western sides of Taiwan with a non-overlapping distribution, indicating the importance of the Central Mountain Range as the major biogeographic barrier. Both clades showed a strong and congruent tendency of demographic or distributional expansion in recent history based on different analyses. Population expansion of such a subtropical lowland species might be a result from a release of available habitat in post-glacial periods.

The Influence of Green Brand Affect on Green Purchase Intentions: The Mediation Effects of Green Brand Associations and Green Brand Attitude.

This study investigates the impact of green brand affect on green purchase intentions and explores the mediation effects of green brand attitude and green brand associations by means of the structural equation model (SEM). There is no previous literature discussing the relationship between brand affect and purchase intentions from the perspective of green marketing. Therefore, this article establishes a green purchase intention framework to fill in the research gap. The research object of this study focuses on Taiwanese consumers who have the purchase experience of information and electronics products in Taiwan. A total of 1000 consumers were randomly selected and 365 valid responses were received. In addition, this research conducted an empirical study using a questionnaire survey and structural equation model (SEM) to verify the research framework. The results show that green brand affect has no direct influence on green purchase intentions. Besides, this study indicates that green brand associations and green brand attitude fully mediate the relationship between green brand affect and green purchase intentions. It implies that green brand affect indirectly influences green purchase intentions via green brand attitude and green brand associations. While companies tend to raise their customers' green purchase intentions, they need to increase their green brand affect, green brand associations, and green brand attitude.

Long-term monitoring reveals invariant clutch size and unequal reproductive costs between sexes in a subtropical lacertid lizard.

Based on 20,000 records representing c. 11,000 individuals from an 8-year capture-mark-recapture (CMR) study, we tested and confirmed a new case of invariant clutch size (ICS) in a sexually dichromatic lacertid lizard, Takydromus viridipunctatus. In the grassland habitat of the early succession stage, females showed strictly low and invariant clutch size, multiple clutches in a breeding season, high reproductive potential, and annual breeding cycles that correspond to the emergence of male courtship coloration. The hatchlings mature quickly, and join the adult cohort for breeding within a few months, whereas adults show low survival rates and a short lifespan, such that most die within one year. Mortality increased in both sexes during the breeding season, especially in females, indicating an unequal cost of reproduction in survival. These life history characters may be explained by two non-exclusive hypotheses of ICS-arboreal hypothesis and predation hypothesis-within the ecological context of their habitat. Our study highlights a confirmed case of ICS, which adapts well to this r-selected grassland habitat that experiences seasonal fluctuation and frequent disturbance.

Deregulation of miR-126-3p in basal-like breast cancers stroma and its clinical significance.

INTRODUCTION: The aim of this study was to investigate miR-126-3p expression in stroma and tumor cells of basal-like breast cancer tissues, in an effort to elucidate the potential effect of miR-126-3p on tumor microenvironment and progress of basal-like breast cancer. METHODS: Expression levels of miR-126-3p in 33 paired basal-like breast cancer tissues were assayed by real-time quantitative PCR. Tumor cells and normal epithelial cell were isolated from ten paired basal-like breast cancer tissues and matched adjacent tissues, separately, using laser capture microdissect(LCM)-based PCR method. Further validated in larger sets were assayed by tissue microarrays (TMA)-based ISH method. RESULTS: MiR-126-3p expression level had no significant differences between basal-like breast cancer subtypes and matched adjacent tissues. However, a decreasing trend of miR-126-3p expression can be found in tumor cells of basal-like subtype, compared with matched adjacent tissues, using LCM-based PCR. Using TMA method, miR-126-3p expression level was the lowest in stroma of basal-like breast cancers among four subtypes (χ2=10.55, P=0.01), and was increasing in stroma of breast cancers compared with fibroadenomas. Furthermore, strong miR-126-3p expression in stroma is significantly associated with HER-2 expression (χ2=4.70, P=0.03) and Ki-67 index. (χ2=4.84, P=0.03), which suggested a potential prognostic value of miR-126-3p in stroma of breast cancer. However, miR-126-3p expression in tumor cells derived from different subtypes hadn't significant clinical values in this study. CONCLUSIONS: the miR-126-3p expression level in breast cancer stroma was associated with different intrinsic subtypes and its correlation with hormone receptor and Ki-67 index shed light on the potential clinical prognostic value of miR-126-3p, in the field of specific breast cancer subtypes.

DIP2C expression in breast cancer and its clinical significance.

INTRODUCTION: The aim of this study was to investigate DIP2C expression in different subtypes of breast cancer tissues and cell lines and its correlation with clinicopathologic and histopathological features, in an effort to elucidate the DIP2C expression profile in breast cancer and its clinical significance. METHODS: Hereby, we investigated the DIP2C expression in breast cancer tissues using TMA-IHC method and the DIP2C expression in breast cell lines using quantitative RT-PCR. RESULTS: DIP2C displayed universal expression, being present in all the breast cancer subtypes. There were more cases that staining weakly in breast cancer tissues (n=79/150, 52.7%) than that in fibroadenomas tissues (n=2/18, 11.1%) and normal tissues (n=2/20, 10.0%) (χ2=21.84, P <0.001). Within different intrinsic subtypes of breast cancer assayed by IHC expression profiles, there were less cases of the strongly staining group in basal-like subtype (n=38/86, 44.2%) and HER-2 subtype (n=6/24, 25.0%) than that in luminal A (14/20, 70%) and luminal B (13/20, 65%) subtypes (χ2=11.77, p=0.008). Furthermore, DIP2C expression was positive correlated with ER (χ2=8.90, p=0.003) and PR expression (χ2=10.94, p=0.001), while negative correlated with EGFR expression (χ2=9.27, p=0.002), in accordance with the results of cell lines with different subtypes. Oncomine database also confirmed that, DIP2C was expressed lower in breast cancer tissues, and could indicate prognosis. CONCLUSION: our data revealed DIP2C expression level decreased in breast cancer, especially in basal-like and HER-2 subtypes, and could be a valuable target for diagnosis on specific subtype of breast cancer.