This panel of variant-specific, quantitative RT-PCR assays detects common EML4-ALK+ variants as well as ALK gene expression level in archival formalin-fixed paraffin-embedded NSCLC specimens. These RT-PCR assays may be useful as an adjunct to the standard fluorescence in situ hybridization assay to better understand biologic variability and response patterns to anaplastic lymphoma kinase inhibitors.
To evaluate the relative safety of blood donations given in response to a major disaster, donor demographics and infectious disease test results were compared for donations made during the 10 days following the October 17, 1989, San Francisco Bay Area earthquake and those made during the preceding 6 months. These comparisons were made for donations given to the regional blood center in the area that was immediately affected by the disaster (Irwin Memorial Blood Centers) and for those given in an unaffected region (Los Angeles/Orange Counties Region, American Red Cross Blood Services). The rate of donation increased more than 200 percent during the 5 days following the earthquake in both the disaster-affected and unaffected regions. Both the disaster-affected and unaffected regions observed significant increases in the proportions of donations by first-time donors, by persons aged 20 to 39 years, and by women. The rates of confirmed positivity for infectious disease markers for post-earthquake donations did not differ significantly from rates for homologous donations given during the preceding 6 months, particularly when the rates were adjusted for the increased representation of first-time donors. Approximately 39 percent of post-earthquake first-time donors gave blood again within the following 6-month period. It is concluded that donations given after major disasters are essentially as safe as routine donations and that active efforts to recruit these donors again can be undertaken without reservation.
Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location impacts the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal colon cancers is not well established. We investigated the associations between tumor location, KRAS and BRAF mutation status, and the mRNA expression of proteins involved in major signaling pathways, including tumor growth (EGFR), angiogenesis (VEGFR2), DNA repair (ERCC1) and fluoropyrimidine metabolism (TS). FFPE tumor specimens from 431 advanced CRC patients were analyzed. The presence of 7 different KRAS base substitutions and the BRAF V600E mutation was determined. ERCC1, TS, EGFR and VEGFR2 mRNA expression levels were detected by RT-PCR. BRAF mutations were significantly more common in the proximal colon (p<0.001), whereas KRAS mutations occurred at similar frequencies throughout the colorectum. Rectal cancers had significantly higher ERCC1 and VEGFR2 mRNA levels compared to distal and proximal colon tumors (p=0.001), and increased TS levels compared to distal colon cancers (p=0.02). Mutant KRAS status was associated with lower ERCC1, TS, EGFR, and VEGFR2 gene expression in multivariate analysis. In a subgroup analysis, this association remained significant for all genes in the proximal colon and for VEGFR2 expression in rectal cancers. The mRNA expression patterns of predictive and prognostic biomarkers as well as associations with KRAS and BRAF mutation status depend on primary tumor location. Prospective studies are warranted to confirm these findings and determine the underlying mechanisms.
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