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Melissa J Fazzari

Publications and source records attributed to Melissa J Fazzari.

4 recordsLinked to original sources
PubMed2006

Comparative isoschizomer profiling of cytosine methylation: the HELP assay.

The distribution of cytosine methylation in 6.2 Mb of the mouse genome was tested using cohybridization of genomic representations from a methylation-sensitive restriction enzyme and its methylation-insensitive isoschizomer. This assay, termed HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR), allows both intragenomic profiling and intergenomic comparisons of cytosine methylation. The intragenomic profile shows most of the genome to be contiguous methylated sequence with occasional clusters of hypomethylated loci, usually but not exclusively at promoters and CpG islands. Intergenomic comparison found marked differences in cytosine methylation between spermatogenic and brain cells, identifying 223 new candidate tissue-specific differentially methylated regions (T-DMRs). Bisulfite pyrosequencing confirmed the four candidates tested to be T-DMRs, while quantitative RT-PCR for two genes with T-DMRs located at their promoters showed the HELP data to be correlated with gene activity at these loci. The HELP assay is robust, quantitative, and accurate and is providing new insights into the distribution and dynamic nature of cytosine methylation in the genome.

Animals↗
PubMed2005

Clinical application of molecular profiling in breast cancer.

Breast cancer is the leading type of cancer and second leading cause of cancer death in women. Breast cancer mortality has declined over the past 10 years largely due to early detection by mammographic screening, but also in part due to the increasing use of adjuvant hormonal therapy and chemotherapy. Indications for adjuvant chemotherapy have now expanded to include women who are at low risk of recurrence, resulting in overtreatment of most women to benefit a few, particularly those with favorable clinical features. New techniques have been evaluated that identify specific molecular signatures that may more accurately predict prognosis than clinical features, and that may also identify individuals who are more likely to benefit from endocrine therapy and/or chemotherapy. This review will focus on the clinical applications of these novel techniques reported to date, and how this may lead to the incorporation of molecular diagnostics into clinical practice. Two prospective, multicenter, multinational Phase III trials evaluating tumor genomic profiling in breast cancer are currently in development, and will be initiated within the forthcoming year. The completion of these important studies will represent the first step toward integrating molecular profiling into treatment selection for adjuvant therapy in breast cancer.

Antineoplastic Agents↗
PubMed2003

Expression of caveolin-1 and caveolin-2 in urothelial carcinoma of the urinary bladder correlates with tumor grade and squamous differentiation.

We immunohistochemically evaluated 94 cases of urothelial carcinoma (UC) of the urinary bladder for the expression of caveolin (Cav)-1 and Cav-2. Neither benign urothelium present in 22 cases nor flat carcinoma in situ present in 10 cases stained for Cav-1 or Cav-2. Thirty-five (37%) of 94 cases and 45 (51%) of 89 cases of UC stained positively for Cav-1 and Cav-2, respectively. The percentages of positive cases for Cav-1 in grades 1, 2, and 3 tumors were 0% (0/6), 0% (0/25), and 56% (35/63), respectively (P < .001), and for Cav-2, 0% (0/6), 13% (3/23), and 70% (42/60), respectively (P < .001). Multivariate analysis showed no significant correlation between tumor stage and Cav-1 or Cav-2 expression after correction for tumor grade. Eighty-two percent (14/17) of cases with squamous differentiation were positive for Cav-1 compared with 43% (20/46) of grade 3 tumors without squamous differentiation (P < .001). These results indicate a positive correlation of the expression of Cav-1 and Cav-2 with tumor grade and squamous features of UC and suggest that Cav-1 and Cav-2 be studied further for a possible role in tumor progression and squamous differentiation.

Adult↗