Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

<p>Abstract</p> <p>Background</p> <p>Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model.</p> <p>Methods</p> <p>To address this issue, we determined the effects of 6 week <it>in vivo </it>acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG) lesions in the transgenic polyomavirus middle T (PyMT) breast cancer mouse model.</p> <p>Results</p> <p>We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the <it>in vivo </it>exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs), demonstrating a relationship between hypoxia and macrophages in an experimental model.</p> <p>Conclusion</p> <p>These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.</p

Current State of Neck Dissection in the United States

The status of the cervical lymph nodes is the most important prognosticator in head and neck squamous cell carcinoma. The neck dissection is both a therapeutic and staging procedure and has evolved to include various types with standardized level designations (I–VI) for lymph node groups: the radical neck dissection, modified radical neck dissection, the selective neck dissection, and the extended neck dissection. The gross and histologic examination of a neck dissection should provide the critical information (size of metastasis, number of lymph nodes involved) for staging purposes. Additionally, extracapsular spread of lymph node metastasis must be reported because of its significance as an adverse prognosticator. Current dilemmas in nodal disease are the detection of micrometastases, isolated tumor cells, and molecular positivity. The significance of these categories of disease is still unclear, though they may explain a subset of the estimated 10% of the regional recurrences in the neck despite pathologic node negativity by traditional methods of evaluation. Sentinel lymph node biopsy has been recently applied to head and neck squamous cell carcinoma to enhance the management of the clinicoradiographically node negative patients. While still investigational, sentinel lymph node biopsy shows promise in selecting patients who require a neck dissection. Rapid highly automated real-time RT-PCR based platforms will allow for incorporation of molecular findings into the intraoperative evaluation of a sentinel lymph node