Comparison of capecitabine and tegafur/gimeracil/oteracil (S-1) in the treatment of advanced breast carcinoma in the elderly

Purpose: To analyse and compare the clinical effects and safety of capecitabine and tegafur/gimeracil/oteracil (S-1) in the treatment of advanced breast carcinoma.Methods: Eighty-four metastatic breast cancer elderly patients for whom first or second-line treatment had failed, were selected from among those admitted to the oncology ward of Binjiang People’s Hospital, China between January 2014 and June 2015. They were randomly divided into S-1 group (n =41) and capecitabine group (n = 41) and received varying doses of those drugs  according to body surface area. Clinical effects, progression-free survival, and incidence of adverse reactions were compared for the two groups following treatment.Results: Disease control rate (CR) in S-1 group was 55.6 %, much higher than 35.1 % observed for capecitabine group (p < 0.05). The disease control rate for the S-1 group was 93.7 %, also much higher than the 70.6 % found in capecitabine group. Survival analysis showed that the median survival times of the two groups did not differ significantly (p > 0.05). Furthermore, some adverse reactions such as myelosuppression and lack of strength, did not differ significantly between the two groups (p > 0.05), whereas others, including leukopenia, nausea and vomiting and hand-foot syndrome were more serious and frequent in capecitabine group than in S-1 group (p < 0.05).Conclusion: Monotherapy with S-1 is more effective than that with capecitabine. Adverse reactions are minimal for both drugs.Keywords: Breast carcinoma, Capecitabine, S-1, Adverse reactions,  Myelosuppression, Leukopenia, Hand-foot syndrom

Qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt

Purpose: To perform a qualitative and quantitative analysis of catechin and quercetin in flavonoids extracted from Rosa roxburghii Tratt.Methods: Total flavonoids were determined using ultraviolet spectrophotometry (UV) at 500 nm. The optimal gradient program started with 15 % methanol and was kept within a period of 0 – 20 min, while 25 % methanol was kept within 20 – 33 min. Subsequently, the concentration of methanol was reduced to 15 % and was held for 10 min until the next injection. Mass spectrometry spray voltage was 4,000 V, ionization temperature 350 °C, atomizer pressure 35 psi, nitrogen flow rate 8 L/min, and mass scan range 200 – 800 m/z. The detection wavelength used for catechin and quercetin was 270 and 368 nm, respectively.Results: Based on the UV results, Rosa roxburghii Tratt content was 73.85 %, which is in agreement with the national standard. Liquid chromatography-mass spectrometry (LC-MS) results indicate that Rosa roxburghii Tratt flavonoids contained quercetin, 34.26 %, with relative standard deviation (RSD) of 2.88 % and catechin content of 2.97 % with RSD of 1.49 %.Conclusion: The proposed measurement method for determining the content of flavonoids in Rosa roxburghii Tratt has the advantage of simplicity, feasibility, good repeatability, and rapid and accurate analysis.Keywords: Rosa roxburghii Tratt, Flavonoids, Catechin, Querceti

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

BACKGROUND: Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear. METHODS: In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients’ survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis. CONCLUSIONS: Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB

Reconsideration of In-Silico siRNA Design Based on Feature Selection: A Cross-Platform Data Integration Perspective

RNA interference via exogenous short interference RNAs (siRNA) is increasingly more widely employed as a tool in gene function studies, drug target discovery and disease treatment. Currently there is a strong need for rational siRNA design to achieve more reliable and specific gene silencing; and to keep up with the increasing needs for a wider range of applications. While progress has been made in the ability to design siRNAs with specific targets, we are clearly at an infancy stage towards achieving rational design of siRNAs with high efficacy. Among the many obstacles to overcome, lack of general understanding of what sequence features of siRNAs may affect their silencing efficacy and of large-scale homogeneous data needed to carry out such association analyses represents two challenges. To address these issues, we investigated a feature-selection based in-silico siRNA design from a novel cross-platform data integration perspective. An integration analysis of 4,482 siRNAs from ten meta-datasets was conducted for ranking siRNA features, according to their possible importance to the silencing efficacy of siRNAs across heterogeneous data sources. Our ranking analysis revealed for the first time the most relevant features based on cross-platform experiments, which compares favorably with the traditional in-silico siRNA feature screening based on the small samples of individual platform data. We believe that our feature ranking analysis can offer more creditable suggestions to help improving the design of siRNA with specific silencing targets. Data and scripts are available at http://csbl.bmb.uga.edu/publications/materials/qiliu/siRNA.html

Paternal Origins and Migratory Episodes of Domestic Sheep

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution