New genetic variant that might improve warfarin dose prediction in African Americans

AIMS

To raise hypotheses with regards to whether genetic variants in the VKORC1, CYP2C9, EPHX1, GGCX and ALB genes might influence warfarin dose in African Americans and Caucasians, independent of the effects of the VKORC1 1173C>T and CYP2C9*2 and *3 variants.

METHODS

From a prospective cohort study, we obtained additional DNA on 36 Caucasian and 22 African American warfarin users who reached maintenance dose and genotyped them for tagSNPs (r² < 0.8) in VKORC1, EPHX1, GGCX and ALB genes, and one exonic CYP2C9 SNP. Linear regression models were fitted to estimate the relationship (P value) between log-transformed maintenance dose and each SNP and the amount of the warfarin dose variability accounted for by each SNP (partial R²).

RESULTS

In African Americans, the VKORC1 rs17886199 A-allele was associated with a lower dose (GG = 46.3 mg and GA = 25.6 mg; P = 0.002), independent of the VKORC1 1173C>T and CYP2C9*2 and *3 variants. Even after applying Bonferroni correction, the P value would still be considered statistically significant. The VKORC1 rs17886199 variant was not found in Caucasians. In Caucasians, the EPHX1 rs1051741 T-allele was associated with a lower dose (CC = 41.3 mg and CT = 30.0 mg; P = 0.04). The latter was no longer statistically significant after applying Bonferroni correction.

CONCLUSIONS

Our pilot study suggests that the VKORC1 rs17886199 variant could influence warfarin maintenance dose among African Americans, even after accounting for the influence of the VKORC1 1173C>T variant. Future studies with a larger sample size will be needed to confirm our findings.     

P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells

p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53-like functions. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Here, we compared for the first time to our knowledge p73 and p63 activation in various breast cancer (BC) cell lines after Adriamycin (ADR) treatment, an agent considered as mandatory in breast cancer chemotherapy. Our study was carried out using 1 p53-proficient BC cell line (MCF7 cells) and 3 BC cell lines deficient in p53 response (MCF7/ADR(IGR), MDA-MB157 and T47D) after ADR-induced genotoxic stress. We report that in cells with no p53 response after ADR treatment, TAp73, but not TAp63 or DeltaN-p73/p63, may replace p53 in triggering not only apoptosis but also cell cycle arrest or DNA repair effectors such as p21, GADD45, 14-3-3sigma and p53R2. We also demonstrate that TAp73 siRNA inhibits the accumulation of TAp73 in response to ADR treatment in MDA-MB157 cells and confers protection against ADR. ADR-induced downregulation of the DeltaNp73 isoform in the T47D cell line with nonfunctional mutant p53 further supports anti-apoptotic function of the isoform antagonistic to both p53 and TA-p73/p63. Exogenous TAp73 and DeltaNp73 overexpression in p53-response-deficient cell lines further confirms these results. cDNA microarray techniques demonstrated that the cellular response induced by p73 during ADR treatment could involve specific genes.     

Primary plasmacytoma of the testis with no evidence of multiple myeloma: a new case report and literature review

Plasmacytomas of the testis are extremely rare tumours, especially when occurring in the absence of a previous or concurrent diagnosis of multiple myeloma. We report a new case of solitary testicular plasmacytoma, with immunohistochemical studies showing monoclonal cytoplasmic production of IgG lambda light chains, in a 51-year-old man who had no evidence of multiple myeloma 3 years after the orchiectomy.     

尤瑞克林通过提高ALDH2表达改善糖尿病合并脑缺血再灌注大鼠神经元损伤

目的 基于乙醛脱氢酶2(ALDH2)变化探讨尤瑞克林对糖尿病合并脑缺血再灌注大鼠神经元损伤的影响.方法 选取60只SPF级SD大鼠,使用体质量编号和随机数表法分为对照组、模型组、尤瑞克林组、尤瑞克林+氨基氰(Cya)组,使用无菌链脲佐菌素(STZ)联合Zea-Longa法制备糖尿病合并脑缺血再灌注大鼠模型,各组大鼠缺血...     

Utilisation des médecines complémentaires chez des patientes tunisiennes atteintes de cancer: enquête réalisée auprès de 150 patientes

Introduction

The aim of this study was to report the frequency and reasons for the use of complementary medicine in patients with cancer, treated in one Tunisian oncology department.

Patients and methods

A questionnaire was completed by a person not involved in the treatment, who questioned patients during follow-up or treatment in one oncology department. One hundred fifty questionnaires could be analysed.

Results

Forty-nine percent of patients were using complementary medicine. Traditional herbal medicines, a honey and black seed mixture and snake meat were the main substances used. The user profile type was young women, and their main reason for using complementary medicine was to cure cancer. Ninety percent of complementary medicine users did not reveal their habits to their oncologist. Most patients were using complementary medicine during their treatment.