High plasma fibrinogen is correlated with poor response to trastuzumab treatment in HER2 positive breast cancer.

Some of HER-2 positive breast cancer patients failed to trastuzumab treatment. Recent reports have indicated the correlation between plasma coagulation parameters and clinical characteristics in breast cancer. The aim of this study was to analyze the role of coagulation parameters in trastuzumab treated patients. Coagulation parameters from trastuzumab treated breast cancer patients were retrospectively studied from 2006 to 2010. The correlation between routine coagulation levels and clinical characteristics were analyzed, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib) and D-dimer (DD). The Kaplan-Meier analysis and Cox regression hazard model were applied to assess their effect on prognosis. Totally 102 hospitalized breast cancer patients who received trastuzumab were collected and followed-up. All patients were HER-2 positive advanced breast cancer, with a median age of 45 years old. Extended PT, APTT, and TT were found in trastuzumab treatment non-effective group, as well as increased Fib and DD. But significant increase was only found in Fib. High Fib status (Fib > 2.88 g/L) was correlated with clinical characteristics, such as pathological grade, and reversely correlated with PTEN expression. More importantly, poor disease-free survival (DFS) and overall survival (OS) to trastuzumab treatment were found in high Fib breast cancer patients. This retrospective study suggests high Fib status was correlated with poor treatment response to trastuzumab. Our findings indicated that Fib > 2.88 should alert physicians to consider a pretreatment for reducing Fib levels before trastuzumab treatment in HER-2 positive breast cancer patients.

DNA Methylation in Genomes of Several Annual Herbaceous and Woody Perennial Plants of Varying Ploidy as Detected by MSAP.

Polyploidization is known to accompany altered DNA methylation in higher plants, which plays an important role in gene expression regulation and maintaining genome stability. While the characteristics of DNA methylation in different polyploid plants are still to be elucidated; here, status of genomic DNA methylation in a series of diploid, triploid, and tetraploid annual herbaceous plants (watermelon and Salvia) and woody perennials (pear, Poplar, and loquat) were explored by methylation-specific amplified polymorphism analysis. The results indicated that levels of DNA methylation in triploid watermelon and Salvia were lower than their diploid parents. In triploid Poplar and pear, higher levels of DNA methylation were detected, and no significant difference was observed between triploid and tetraploid in all tested materials. Further data analysis suggested that about half of the total detected sites underwent changes of DNA methylation patterns in triploid watermelons and Salvia, as well as an obvious trend towards demethylation. However, the changes of DNA methylation patterns in three triploid woody perennials were only 17.54-33.40%. This implied that the characteristics of DNA methylation are significantly different during the polyploidization of different plant species. Furthermore, the results suggested that the level of DNA methylation was nonlinearly related to the ploidy level, and triploid plants displayed more interesting DNA methylation status. The characteristics and possible functions of DNA methylation in different ploidy series are further discussed.

TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3) TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.