Inhibition of interferon-alpha/beta induction in L-929 cells by benzene and benzene metabolites

Murine L-929 cells were treated with benzene or a series of benzene metabolites, washed and then interferon-alpha/beta was induced with polyriboinosinic-polyribocytidylic acid. Exposure of the cells to benzene or phenol, a monocyclic metabolite of benzene, did not affect interferon-alpha/beta induction. However, exposure of the cells to p-benzoquinone, hydroquinone or catechol, dihydroxy- and diketo-metabolites of benzene, resulted in a severe inhibition of interferon-alpha/beta production. There was no significant loss of viability of the cell cultures. Additional studies with p-benzoquinone indicated that inhibition of interferon-alpha/beta was reversible and could be abrogated by addition of reduced glutathione to the cell cultures.     

Is EGFR really a therapeutic target in head and neck cancers?

Epidermal growth factor receptor (EGFR) is overexpressed in 90% to 100% of squamous cell carcinoma of the head and neck (SCCHN). The overexpression of EGFR and its ligand transforming growth factor is associated with poorer survival. EGFR inhibitors such as Cetuximab (Erbitux) have shown a significant antitumoral effect in SCCHN and has improved locoregional control and as well as survival. Even though there was some success with Cetuximab, work with other EGFR inhibition has not been very fruitful and not really shown any promise. Mechanism of action of Cetuximab could be immune-mediated rather than EGFR inhibition and EGFR may not necessarily be a therapeutic target in SCCHN.     

A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes

BACKGROUND:

The authors prospectively evaluated the performance of a proprietary molecular testing platform using one‐step nucleic acid amplification (OSNA) for the detection of metastatic carcinoma in sentinel lymph nodes (SLNs) in a large multicenter trial and compared the OSNA results with the results from a detailed postoperative histopathologic evaluation (reference pathology) and from intraoperative imprint cytology (IC).

METHODS:

In total, 1044 SLN samples from 496 patients at 11 clinical sites were analyzed. Alternate 1‐mm sections were subjected to either detailed histopathologic evaluation with hematoxylin and eosin and pancytokeratin immunostaining or the OSNA Breast Cancer System, which was calibrated to detect tumor deposits >0.2 mm by measuring cytokeratin 19 messenger RNA. At 7 sites, IC was performed before permanent section. The OSNA results were classified as negative (<250 copies/μL), micrometastases (from ≥250 to <5000 copies/μL), or macrometastases (≥5000 copies/μL).

RESULTS:

The sensitivity and specificity of the OSNA breast cancer system compared with reference pathology were 77.5% (95% confidence interval, 69.7%‐84.2%) and 95.8% (95% confidence interval, 94.3%‐97.0%), respectively, before discordant case analyses (DCA). Sensitivity and specificity after DCA were 82.7% and 97.7%, and final concordance was 95.8%. Performance for invasive lobular carcinoma demonstrated 88.2% sensitivity (95% confidence interval, 63.6%‐98.5%) and 98.5% specificity (95% confidence interval, 92%‐100%). The sensitivity of OSNA was significantly better than that of IC (80% vs 63%; P = .0229).

CONCLUSIONS:

The OSNA breast cancer system proved to be highly accurate for the detection of metastatic breast cancer in axillary SLNs. Sensitivity was comparable to that predicted for conventional postoperative histologic examination at 2‐mm intervals and was significantly more sensitive than IC. Automation, semiquantitative results enabling the differentiation of macrometastasis and micrometastasis, and rapid results render the assay suitable for intraoperative and/or permanent evaluation of SLNs. Cancer 2011. © 2011 American Cancer Society.     

Hip bone density predicts breast cancer risk independently of Gail score: results from the Women's Health Initiative

BACKGROUND: The Gail model has been commonly used to estimate a woman's risk of breast cancer within a certain time period. High bone mineral density (BMD) is also a significant risk factor for breast cancer, but it appears to play no role in the Gail model. The objective of the current study was to investigate whether hip BMD predicts postmenopausal breast cancer risk independently of the Gail score. METHODS: In this prospective study, 9941 postmenopausal women who had a baseline hip BMD and Gail score from the Women's Health Initiative were included in the analysis. Their average age was 63.0 +/- 7.4 years at baseline. RESULTS: After an average of 8.43 years of follow-up, 327 incident breast cancer cases were reported and adjudicated. In a multivariate Cox proportional hazards model, the hazards ratios (95% confidence interval [95% CI]) for incident breast cancer were 1.35 (95% CI, 1.05-1.73) for high Gail score (>or=1.67%) and 1.25 (95% CI, 1.11-1.40) for each unit of increase in the total hip BMD T-score. Restricting the analysis to women with both BMD and a Gail score above the median, a sharp increase in incident breast cancer for women with the highest BMD and Gail scores was found (P < .05). CONCLUSIONS: The contribution of BMD to the prediction of incident postmenopausal breast cancer across the entire population was found to be independent of the Gail score. However, among women with both high BMD and a high Gail score, there appears to be an interaction between these 2 factors. These findings suggest that BMD and Gail score may be used together to better quantify the risk of breast cancer.     

Covalent binding of acrylonitrile to specific rat liver glutathione S-transferases in vivo.

Acrylonitrile (AN) is an industrial vinyl monomer that is acutely toxic. When administered to rats, AN covalently binds to tissue proteins in a dose-dependent but nonlinear manner [Benz, F. W., Nerland, D. E., Li, J., and Corbett, D. (1997) Fundam. Appl. Toxicol. 36, 149-156]. The nonlinearity in covalent binding stems from the fact that AN rapidly depletes liver glutathione after which the covalent binding to tissue proteins increases disproportionately. The identity of the tissue proteins to which AN covalently binds is unknown. The experiments described here were conducted to begin to answer this question. Male Sprague-Dawley rats were injected subcutaneously with 115 mg/kg (2.2 mmol/kg) [2,3-(14)C]AN. Two hours later, the livers were removed, homogenized, and fractionated into subcellular components, and the radioactively labeled proteins were separated on SDS-PAGE. One set of labeled proteins was found to be glutathione S-transferase (GST). Specific labeling of the mu over the alpha class was observed. Separation of the GST subunits by HPLC followed by scintillation counting showed that AN was selective for subunit rGSTM1. Mass spectral analysis of tryptic digests of the GST subunits indicated that the site of labeling was cysteine 86. The reason for the high reactivity of cysteine 86 in rGSTM1 was hypothesized to be due to its potential interaction with histidine 84, which is unique in this subunit.     

Paget's disease of the breast: What the radiologist may expect to find

Paget's disease of the nipple is characterized by the presence of Paget's cells in the epidermis of the nipple or areola. Two case reports of Paget's disease are described and used to highlight unusual features of the disease. The literature on the radiographic and pathologic findings of this disease is reviewed.