Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results.

Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells.

Safety and efficacy of human embryonic stem cell-derived astrocytes following intrathecal transplantation in SOD1 and NSG animal models.

Background: Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease characterized by the loss of MNs in the central nervous system. As MNs die, patients progressively lose their ability to control voluntary movements, become paralyzed and eventually die from respiratory/deglutition failure. Despite the selective MN death in ALS, there is growing evidence that malfunctional astrocytes play a crucial role in disease progression.

Mutation screening using fluorescence multiplex denaturing gradient gel electrophoresis (FMD): detecting mutations in the BRCA1 gene.

Fluorescent multiplex denaturing gradient gel electrophoresis (FMD) is a mutation screening technique designed to detect unknown as well as previously identified mutations. FMD constitutes a recent modification of the standard denaturing gradient gel electrophoresis (DGGE) technique, which combines multiplex PCR amplification of target DNA using fluorescently labeled primers with DGGE separation of the amplicon mixture, allowing immediate identification of sequence variants by wet gel scanning. FMD permits the simultaneous detection of small insertions, deletions and single nucleotide substitutions among multiple DNA fragments (up to 480 fragments) from 96 samples in parallel for each run.

A fluorescent multiplex-DGGE screening test for mutations in the BRCA1 gene.

Screening for mutations in the BRCA1 gene is challenging because of the wide spectrum of mutations found in this large gene. As the extensive exon 11 is commonly screened by the protein truncation test (PTT), here a fluorescent multiplex denaturing gradient gel electrophoresis (FMD) mutation screening technique was developed to test the remaining numerous small exons and splice sites of the gene. The method is based upon the use of an efficient multiplex polymerase chain reaction (PCR) amplification of the target regions, followed by denaturing gradient gel electrophoresis (DGGE) separation of the amplicon mixture, and the immediate achievement of results by wet gel scanning.

Cancer incidence in a population of Jewish women at risk of ovarian cancer.

Purpose: To evaluate the incidence and clinical characteristics of ovarian and other cancers in a cohort of women at risk of developing ovarian cancer.

Patients And Methods: The Gilda Radner Ovarian Cancer Detection Program in Los Angeles, CA, was established in 1991 to study the efficacy of screening in the early detection of ovarian cancer. We present findings from a historical cohort of 290 Jewish women who were offered BRCA testing for three common founder mutations (BRCA1 185delAG and 5382insC and BRCA2 6174delT).

A genetic epidemiological study of carcinoma of the fallopian tube.

Objective: The goal of this work was to evaluate the importance of genetic factors in the etiology of fallopian tube cancer.

Methods: All pathologically confirmed cases of fallopian tube cancer diagnosed in Ontario from 1990 to 1998 were identified from the records of the Ontario Cancer Registry. Living patients were approached to provide information about their family history and to provide a blood sample for testing for mutations in BRCA1 and BRCA2.

Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer.

A population-based series of 649 unselected incident cases of ovarian cancer diagnosed in Ontario, Canada, during 1995-96 was screened for germline mutations in BRCA1 and BRCA2. We specifically tested for 11 of the most commonly reported mutations in the two genes. Then, cases were assessed with the protein-truncation test (PTT) for exon 11 of BRCA1, with denaturing gradient gel electrophoresis for the remainder of BRCA1, and with PTT for exons 10 and 11 of BRCA2.

Primary node negative breast cancer in BRCA1 mutation carriers has a poor outcome.

Background: The association between BRCA1 germ-line mutations and breast cancer prognosis is controversial. A historical cohort study was designed to determine the prognosis for women with axillary lymph node negative hereditary breast cancer.

Patients And Methods: We tested pathology blocks from 118 Ashkenazi Jewish women with axillary lymph node negative breast cancer for the presence of the two common BRCA1 founder mutations, 185delAG and 5382insC.

A rapid fluorescent multiplexed-PCR analysis (FMPA) for founder mutations in the BRCA1 and BRCA2 genes.

Mutations of the BRCA1 and BRCA2 genes account for approximately 80% of hereditary breast/ovarian cancer families, but the size of these two genes makes mutation analysis time-consuming and technically challenging. In some populations such as the Ashkenazi Jewish and the French-Canadian, a small number of recurrent founder mutations account for the majority of mutations in cancer families. We have therefore developed two rapid genetic screening tests, which allow us to detect three frequent frameshift mutations in the Ashkenazi Jewish population and five frameshift mutations in the French-Canadian population.

Could the 185delAG BRCA1 mutation be an ancient Jewish mutation?

A predominant mutation within the BRCA1 predisposition gene, 185delAG, has been detected in about 1% of the Ashkenazi population, considered a high-risk group for breast and ovarian cancers. We examined 639 unrelated healthy Jews of Iraqi extraction, a presumed low-risk group, for the existence of this mutation. Three individuals were identified as 185delAG mutation carriers, and haplotype analysis of the Iraqi mutation carriers revealed that 2 of the Iraqis shared a common haplotype with 6 Ashkenazi mutation carriers, and 1 had a haplotype which differed by a single marker.