Daniel P.B.,University of Otago |
Morgan T.,University of Otago |
Alanay Y.,Hacettepe University |
Bijlsma E.,Leiden University |
And 22 more authors.
Human Mutation | Year: 2012
Dominant missense mutations in FLNB, encoding the actin-cross linking protein filamin B (FLNB), cause a broad range of skeletal dysplasias with varying severity by an unknown mechanism. Here these FLNB mutations are shown to cluster in exons encoding the actin-binding domain (ABD) and filamin repeats surrounding the flexible hinge 1 region of the FLNB rod domain. Despite being positioned in domains that bind actin, it is unknown if these mutations perturb cytoskeletal structure. Expression of several full-length FLNB constructs containing ABD mutations resulted in the appearance of actin-containing cytoplasmic focal accumulations of the substituted protein to a degree that was correlated with the severity of the associated phenotypes. In contrast, study of mutations leading to substitutions in the FLNB rod domain that result in the same phenotypes as ABD mutations demonstrated that with only one exception disease-associated substitutions, surrounding hinge 1 demonstrated no tendency to form actin-filamin foci. The exception, a substitution in filamin repeat 6, lies within a region previously implicated in filamin-actin binding. These data are consistent with mutations in the ABD conferring enhanced actin-binding activity but suggest that substitutions affecting repeats near the flexible hinge region of FLNB precipitate the same phenotypes through a different mechanism. © 2012 Wiley Periodicals, Inc.
Hajikhan Mirzaei M.,Sarem Womens Hospital |
Hajikhan Mirzaei M.,Razi University |
Noruzinia M.,Sarem Womens Hospital |
Noruzinia M.,Tarbiat Modares University |
And 5 more authors.
Cell Journal | Year: 2012
Objective: Breast cancer is one of the most common malignancies in women worldwide. It is caused by a number of genetic and epigenetic factors. Aberrant hypermethylation of the promoter regions in specific genes is a key event in the formation and progression of breast cancers as well as the DBC2 gene, as a tumor suppressor gene. Different studies show that the DBC2 gene is inactivated through epigenetic mechanisms such as methylation in its promoter region. In this study, authors have tried to analyze methylation status in the promoter region of DBC2 gene in affected women and healthy controls. Materials and Methods: In this experimental study, we evaluated the methylation status of DBC2 gene with nested methylation-specific PCR (MSPCR) using specific methylated and unmethylated primer sets, in three separate PCR reactions. We used 50 tissue and blood samples of patients with breast cancer, 5 normal tissues and also 30 normal blood samples. Results were evaluated by the Mann-Whitney test, SPSS 16.0 statistical software. Results: Nested MSPCR results demonstrated that the frequency of the DBC2 promoter region methylation status in tumor and blood samples of the affected patients was significantly higher than that of the corresponding normal controls. Conclusion: DBC2 gene inactivation by methylation of CpG islands in the promoter region probably is a crucial step in the process of cell proliferation and susceptibility to different cancers, including breast cancer. Our study provides new evidence that aberrant methylation of the DBC2 gene is involved in the tumorigenesis of breast cancer. DNA methylation in this gene is proven to be a potential marker for tumor diagnosis and prognosis, as well as a novel therapeutic target.
Saremi A.,Sarem Womens Hospital |
Saremi A.,Sarem Cell Research Center |
Bahrami H.,Sarem Womens Hospital |
Bahrami H.,Sarem Cell Research Center |
And 5 more authors.
Reproductive BioMedicine Online | Year: 2014
The advised treatment for severe adenomyosis is hysterectomy, but for patients wishing to preserve their uterus, novel conservative surgery, adenomyomectomy, can be performed. The technique needs to be developed to reduce spontaneous uterine rupture, adhesion and recurrence rates. This study aimed to investigate the safety and therapeutic outcomes of adenomyomectomy. Prospectively, 103 Iranian patients with documented severe adenomyosis were candidates for adenomyomectomy over a period of 7 years (from April 2004 to March 2011). The surgical procedure involved resection of adenomatosis lesions with a thin (≤0.5 cm) margin (wedge-shaped removal) after sagittal incision in the uterine body. Reconstruction of the layers was performed and inverted sutures were used for the serosal layer ends. Of 103 patients, 55.34% presented with infertility, 16.50% with IVF failure, 8.74% with recurrent abortion and 19.42% with abnormal uterine bleeding. Of 70 patients who attempted pregnancy, naturally (n = 21) or by assisted reproduction treatment (n = 49), 30% achieved a clinical pregnancy, and 16 resulted in a full-term live birth. Dysmenorrhoea and hypermenorrhoea were reduced post surgery. Only one patient had relapsed adenomyosis. Adenomyomectomy is a conservative and effective treatment for adenomyosis. This study describes an efficient procedure to treat severe adenomyosis. Adenomyosis is uterine thickening that occurs when endometrial tissue, which normally lines the uterus, moves into the outer muscular walls of the uterus. The advised treatment for the severe forms of adenomyosis is hysterectomy (removal of the patient's uterus), but for the patient who wishes to preserve her uterus, a novel conservative surgery referred to as 'adenomyomectomy' (removal of the abnormal tissues) can be performed. This technique must be developed for reduction of spontaneous uterine rupture, adhesions and recurrence rate. This study aims to investigate the safety and therapeutic outcomes of adenomyomectomy. Prospectively, 103 Iranian patients with documented severe adenomyosis were candidates for adenomyomectomy over a period of 7 years (from April 2004 to March 2011). The surgical procedure was resection of adenomatosis lesions with a thin margin. Of 103 patients, 55.34% presented with infertility, 16.50% with IVF failure, 8.74% with recurrent abortion and 19.42% with abnormal uterus bleeding. Of 70 patients who attempted pregnancy either naturally (n = 21) or using assisted reproduction technology (n = 49), 30% became pregnant, and 16 pregnancies reached full term. There was a significant reduction in dysmenorrhoea and hypermenorrhoea. Only one patient had relapsed adenomyosis. Based on these results, we conclude that adenomyomectomy is the conservative and effective option to treat adenomyosis with preservation of the uterus. The procedure described in this study can be an efficient procedure to treat severe adenomyosis. © 2014, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.