Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma (SCC). This study aimed to elucidate transcriptional changes leading to malignancy by investigating differentially expressed genes in squamous cells present in a SCC compared with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated and a SCC cell line was commercially purchased. mRNA from all three samples was isolated and its expression was quantified using RNASeq. A threshold of log2fold change >2-fold in either direction was considered "differentially expressed." Gene expression analysis revealed distinct differences in gene expression in MU cells compared with EC (665 genes), EC and SCC (1673 genes). Enrichment analysis confirmed that pathways most affected included 1) elevation of genes associated with extracellular matrix organization/degradation, 2) activation of DNA damage, and 3) activation of cytokine signaling. Our analysis revealed two key insights about chronic wound microenvironment conducive to ulceration. First, in EC vs. MU comparison, downregulation of Collagen and Matrix metalloproteinase families suggests chronically impaired extracellular matrix turnover giving rise to a fibrotic microenvironment. Second, in SCC vs. MU comparison, dysregulation of cadherin-mediated cell-cell adhesions is suggestive of epithelial-to-mesenchymal transitions, similar to those during development. Acquisition of epithelial-to-mesenchymal transition may underlie the high metastatic rate in MU tumors. Taken together, this sheds light on mechanisms that underlie the divergent clinical features of these cutaneous cancers.
Rabbit hind limb musculature implanted with nine ferromagnetic nickel-copper alloy needles was inductively heated in a 120 kHz oscillating magnetic field. Rabbits were heated every third day for a total of three 30 min heating periods. Ferromagnetic needles with Curie points of 42 degrees C, 45 degrees C, and 48 degrees C were used. Fourteen days following the third heating the animals were sacrificed and the tissues processed for microangiography and histopathology. Implanted muscle heated rapidly and achieved a stable temperature within 10 min. Two weeks after heating for three 30 min heat cycles at temperatures above 47.1 degrees C, both vasculature destruction and muscle necrosis were noted. However, at temperatures below 45.5 degrees C, histopathologic and microangiographic findings were indistinguishable from unheated, implanted controls. Myocentric granuloma formation surrounding the thermoseed tracks with vascular preservation characterized tissue at a steady-state temperature between 45.5 degrees C and 47.1 degrees C. Nickel-copper alloy thermoseeds were effective at producing reproducible, localized interstitial hyperthermia. Chronic vascular and histopathologic alterations correlated closely with previous steady-state temperatures.
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