ABSTRACT
The 7th edition of the AJCC Cancer Staging Manual represents a dramatic shift in the way that cutaneous squamous cell carcinoma (cSCC) is staged, in that it is first attempt to incorporate evidence-based medicine into the staging guidelines for cSCC. In our opinion, the changes made to the seventh edition represent a significant improvement over previous editions and will ultimately lead to improved patient stratification, more accurate prognostic data, and a better framework to guide clinical decision making. However, there are a number of issues within the latest guidelines that require clarification or are impractical for clinical practice. The purpose of this paper is to highlight the key changes to the 6th edition staging manual as they pertain to cSCC, to point out impractical component of the 7th edition and/or aspects that require further clarification, and to make recommendations that address any current shortcomings to improve subsequent editions. Specific focus will be given to the inclusion of separate guidelines for cSCC and Merkel cell carcinoma (MCC), the incorporation of high-risk factors as modifiers of T stage, the addition of new guidelines for advanced T stage, and the changes in stratification of lymph node status. This paper is modified from a more comprehensive treatment of the staging of nonmelanoma skin cancer by Warner and Cockerell entitled "The new 7th edition American joint committee on cancer staging of cutaneous nonmelanoma skin cancer: a critical review," in the American Journal of Clinical Dermatology (paper accepted, pending publication).
ABSTRACT
Neurodegenerative diseases as a class do not have effective pharmacotherapies. This is due in part to a poor understanding of the pathologies of the disease processes, and the lack of effective medications. Gene delivery is an attractive possibility for treating these diseases. For the paradigm to be effective, efficient, safe and versatile vectors are required. In this study we evaluated three plasmid delivery systems for transgene expression in the rat hippocampus. Two of these systems were designed to have enhanced intracellular biodegradability. It was hypothesized that this system would be less toxic and could increase the free (non-vector) associated plasmids within the cell, leading to increased transgene activity. Polyethylenimine (PEI) and r-AAV-2 (recombinant adeno associated virus-2) were used as positive, non-viral and viral controls respectively, in the in vivo experiments. The results from the studies indicate there is a distinct difference between the various vectors in terms of total cells transfected, type of cell transfected, and toxicity. Non-viral systems were effective at transfecting both neurons and glia cells within the hippocampus, while the r-AAV-2 transfected mainly neurons. In summary, plasmid-mediated systems are effective for transgene expression within the brain and deserve further study.
