A Comparative Immunohistochemical Study of Presence and Distribution Pattern of Stromal Myofibroblast in Oral Dysplasia and in Different Grades of Oral Squamous Cell Carcinoma.

AIMS AND OBJECTIVES: Squamous cell carcinoma (SCC) is a common oral malignancy with a poor survival rate. Early tumorigenesis is marked by transdifferentiation of fibroblasts to myofibroblasts (MFs), which is supported by growth factors and cytokines expressed by tumor cells. The expression of alpha-smooth muscle actin (αSMA) marker correlates with the activation of MFs. This study was undertaken to compare the frequency and distribution of αSMA immunoexpression in oral epithelial dysplasia (OED) and OSCC. MATERIALS AND METHODS: This study was conducted on samples collected from patients with oral epithelial dysplasia and oral SCC who visited Rajarajeswari Dental College and Hospital, Bengaluru. Tissue sections were subjected to Immunohistochemistry using αSMA marker, and cells were counted. The obtained data was subjected to Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: On performing Kruskal-Wallis test and Mann-Whitney U-test between the three groups (normal oral mucosa, OED, and OSCC) statistically significant result was found in the frequency between OED and OSCC and between normal tissue and OSCC. On comparing the distribution pattern, statistically significant result was found between OED and OSCC and between normal tissue and OSCC. CONCLUSION: The expression of MFs increases as the disease progresses from high-grade epithelial dysplasia to invasive OSCC. Poorly differentiated SCC showed more attendance of positive MFs in the stroma than other grades of OSCC. The rise in the number of αSMA-positive MFs and change in distribution pattern in OSCC can be associated with tumor invasive characteristics. Thus, the proliferation of MFs may be used as a stromal marker of premalignancy and malignancy.

Evaluation of hyaluronic acid-protein conjugates for polymer masked-unmasked protein therapy.

Bioresponsive polymers may effectively be utilized to enhance the circulation time and stability of biologically active proteins and peptides, while reducing their immunogenicity and toxicity. Recently, dextrin-epidermal growth factor (EGF) conjugates, which make use of the Polymer-masked UnMasked Protein Therapy (PUMPT) concept, have been developed and shown potential as modulators of impaired wound healing. This study investigated the potential of PUMPT using hyaluronic acid (HA) conjugates to mask activity and enhance protein stability, while allowing restoration of biological activity following triggered degradation. HA fragments (Mw ∼90,000g/mol), obtained by acid hydrolysis of Rooster comb HA, were conjugated to trypsin as a model enzyme or to EGF as a model growth factor. Conjugates contained 2.45 and 0.98% (w/w) trypsin or EGF, respectively, and contained <5% free protein. HA conjugation did not significantly alter trypsin's activity. However, incubation of the conjugate with physiological concentrations of HAase increased its activity to ∼145% (p<0.001) that of the free enzyme. In contrast, when HA-EGF conjugates were tested in vitro, no effect on cell proliferation was seen, even in the presence of HAase. HA conjugates did not display typical masking/unmasking behavior, HA-trypsin conjugates exhibited ∼52% greater stability in the presence of elastase, compared to free trypsin, demonstrating the potential of HA conjugates for further development as modulators of tissue repair.