Faculty Bibliography

BACKGROUND: Although it is clear that radiation therapy can cause tissue injury, the degree of injury that is observed clinically can be highly variable. It is possible that variability in the methods by which ionizing radiation is delivered can contribute to some of the observed variability. Thus, the purpose of this study was to assess the effects of various fractionation schedules on the growth and differentiation potential of isolated mesenchymal stem cells in vitro. METHODS: Isolated mesenchymal stem cells (triplicate studies) were exposed to a dose of 12 Gy of ionizing radiation as a single dose, in two doses of 6 Gy, or in six doses of 2 Gy. Cellular proliferation and the potential for differentiation along the bone and fat lineage were assessed. Potential mechanisms for injury and protection were evaluated by analyzing the expression of p21 and manganese superoxide dismutase. RESULTS: Delivery of radiation in multiple doses confers significant radioprotection to mesenchymal stem cell proliferation and potential for differentiation. In contrast, delivery of 12 Gy of radiation as a single dose or as two equal doses of 6 Gy results in marked deficiencies in cellular proliferation and potential for multilineage cellular differentiation. CONCLUSIONS: The authors have demonstrated that even minor alterations in fractionation of radiation dose can result in significant effects on the potential of mesenchymal stem cells to differentiate. These findings imply that at least some of the variability in tissue damage after radiation therapy observed clinically may be attributable to differences in the delivery of ionizing radiation.

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize to the neck, an event that dramatically worsens prognosis. Metastasis occurs even in earlier stages when no neck lymph node involvement is clinically detectable (N0). Management of the N0 neck, namely when and how to electively treat, has been debated extensively. This article presents the controversies surrounding management of the N0 neck, and the benefits and pitfalls of different approaches used in evaluation and treatment. As current methods of assessing the risk for occult metastasis are insufficiently accurate and prone to underestimation of actual risk, and because selective neck dissection (SND) is an effective treatment and has minimal long-term detriment to quality of life, the authors believe that all patients who have oral SCC, excluding lip SCC, should be prescribed elective treatment of the neck lymphatics. However, this opinion remains controversial. Because of the morbidity of radiation therapy and because treatment of the primary tumor is surgical, elective neck dissection is the preferred treatment. In deciding the extent of the neck dissection, several retrospective studies and one randomized clinical trial have shown SND of levels I through III to be highly efficacious

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process

Previous neurophysiological studies of the frontal eye field (FEF) in monkeys have focused on its role in saccade target selection and gaze shift control. It has been argued that FEF neurons indicate the locations of behaviorally significant visual stimuli and are not inherently sensitive to specific features of the visual stimuli per se. Here, for the first time, we directly examined single cell responses to simple, two-dimensional shapes and found that shape selectivity exists in a substantial number of FEF cells during a passive fixation task or during the sample, delay (memory), and eye movement periods in a delayed match to sample (DMTS) task. Our data demonstrate that FEF neurons show sensory and mnemonic selectivity for stimulus shape features whether or not they are behaviorally significant for the task at hand. We also investigated the extent and localization of activation in the FEF using a variety of shape stimuli defined by static or dynamic cues employing functional magentic resonance imaging (fMRI) in anesthetized and paralyzed monkeys. Our fMRI results support the electrophysiological findings by showing significant FEF activation for a variety of shape stimuli and cues in the absence of attentional and motor processing. This shape selectivity in FEF is comparable to previous reports in the ventral pathway, inviting a reconsideration of the functional organization of the visual system.