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Mount Sinai, United States

Akbari M.R.,University of Toronto | Donenberg T.,University of Miami | Lunn J.,Doctors Hospital | Curling D.,Princess Margaret Hospital | And 5 more authors.
Clinical Genetics | Year: 2014

We sought to identify the full range of founder mutations in BRCA1 and BRCA2 in the Bahamas and to estimate the proportion of all BRCA1 and BRCA2 mutations that are accounted for by founder mutations. We studied 214 Bahamian women with invasive breast cancer, unselected for age or family history. A founder mutation had previously been identified in 49 patients. We conducted full sequencing of the BRCA1 and BRCA2 genes and multiplex ligation-dependent probe amplification (MLPA) for 156 patients. A novel founder mutation in BRCA2 (exon 17 818delA) was seen in four different patients and five other unique mutations in BRCA1 and BRCA2, including a large deletion (exons 8-9) in BRCA1. In total, a mutation was seen in 58 of the 214 patients (27%); 92% of carriers carried one of the seven founder mutations. Approximately 27% of unselected cases of breast cancer in the Bahamian population are attributable to a mutation in BRCA1 or BRCA2, a prevalence which far exceeds that of any other country. The majority of women who carry a mutation in the Bahamas, carry one of the seven founder mutations, making it possible to offer genetic testing to all women at risk for breast cancer in the Bahamas. © 2013 John Wiley & Sons A/S.

Donenberg T.,University of Miami | Lunn J.,Doctors Hospital | Curling D.,Princess Margaret Hospital | Turnquest T.,Princess Margaret Hospital | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2011

The Bahamas is a group of islands in the Caribbean with a high incidence of early onset breast cancer. In isolated populations, the identification of founder mutations in cancer predisposing genes may facilitate genetic testing and counseling. To date, six distinct BRCA1 mutations have been found in patients from cancer families from the Bahamas. The frequencies of these mutant alleles have not been measured in a large series of unselected breast cancer patients from Bahamas. We studied 214 Bahamian women with invasive breast cancer, unselected for age or family history of cancer. All patients were screened for six mutations in the BRCA1 gene that have previously been reported in cancer patients from the Bahamas. A mutation was identified in 49 of the 214 breast cancer patients (23%). The mutation frequency was particularly high in women diagnosed before age 50 (33%) in women with a first-degree relative with breast or ovarian cancer (41%) and in women with bilateral breast cancer (58%). Approximately 23% of unselected cases of breast cancer in the Bahamian population are attributable to a founder mutation in the BRCA1 gene-this is the highest reported mutation prevalence for any country studied to date. Genetic testing for these mutations is advisable for all women diagnosed with breast cancer in the Bahamas. © 2010 Springer Science+Business Media, LLC.

Chistiakov D.A.,Mount Sinai Comprehensive Cancer Center | Chistiakov D.A.,Research Center for Childrens Health | Orekhov A.N.,Russian Academy of Sciences | Bobryshev Y.V.,University of New South Wales | Bobryshev Y.V.,University of Western Sydney
Cellular and Molecular Life Sciences | Year: 2015

Circulating extracellular vesicles (EVs) comprise a heterogeneous population of vesicular structures. According to the current paradigm, there are three types of EVs, including exosomes, microvesicles and apoptotic bodies, that are differentiated in their size, formation, and release mechanisms. EVs were shown to act as a 'post service' that serves a long-distance delivery of complex cellular messages. The cargo of EVs consists of a variety of biomolecules including proteins, DNA, mRNA, and non-coding RNA. In normal or pathological conditions, EVs deliver various molecules to the recipient cells. Those molecules greatly vary depending on the microenvironmental stimuli. In proinflammatory conditions such as atherosclerosis and other cardiovascular diseases, EVs derived from vascular endothelial cells, vascular smooth muscle cells, macrophages, and other circulating immune cells mainly possess proinflammatory properties. However, the capacity of circulating EVs to stably maintain and deliver a variety of biomolecules makes these microparticles to be a promising therapeutic tool for treatment of cardiovascular pathology. To date, circulating EVs were evaluated to be as a source of valuable diagnostic and prognostic biomarkers such as microRNA. Circulating EVs keep a great therapeutic potential to serve as vehicles for targeted therapy of cardiovascular diseases. © 2015 Springer Basel.

Soares H.P.,Mount Sinai Medical Center | Lutzky J.,Mount Sinai Comprehensive Cancer Center
Expert Opinion on Biological Therapy | Year: 2010

Importance of the field: Immunotherapy for cancer has been investigated for several decades, achieving limited success. The development of effective new immunotherapeutic agents has reignited interest in the filed. Intralesional injection of plasmids in order to transfect genes capable of stimulating or augmenting immune recognition and destruction of tumors is a relatively new approach. Areas covered in this review: Our objective is to discuss the role velimogene aliplasmid (Allovectin-7®, Vical Incorporated), a plasmidlipid complex containing the DNA sequences encoding HLA-B7 and β2 microglobulin, as an immunotherapeutic agent. What the reader will gain: Intralesional velimogene aliplasmid induces anti-tumor responses in a proportion of melanoma patients with locoregional and limited distant metastases. Preclinical data and the results of Phase I, II and III clinical trials with this drug are reviewed. The limited data in other malignancies is also reviewed. Velimogene aliplasmid in humans appears safe, with minimal drug-related adverse events. Take home message: Velimogene aliplasmid has activity in melanoma with local and limited distant disease associated with an excellent safety profile. The activity of this approach is also being investigated in other malignancies. © 2010 Informa UK Ltd.

Bobryshev Y.V.,University of New South Wales | Orekhov A.N.,Russian Academy of Sciences | Chistiakov D.A.,Mount Sinai Comprehensive Cancer Center
Cell and Tissue Research | Year: 2015

Stem/progenitor cells residing in the vascular wall of post-natal vessels play a crucial role in angiogenesis and vascular regeneration after damage. There are four major populations of vascular-resident stem/progenitor cells with differentiated clonogenic and proliferative potential, namely mesenchymal stem cells, pericytes, endothelial progenitor cells, and smooth muscle progenitor cells. These progenitors reside in vascular stem cell niches, which are more likely to be in the adventitia, a vascular wall layer in which increased concentration of stem cell surface markers has been shown. Indeed, vascular resident progenitors are not uniformly distributed across the vessel wall and the circulatory system. The heterogeneity of such a distribution could contribute to the differentiated susceptibility of various vessel regions to chronic vascular diseases such as atherosclerosis. In cardiovascular pathology, adult vascular resident progenitors could play either a negative or a positive role. © 2015, Springer-Verlag Berlin Heidelberg.

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