Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)-The Effect of Celecoxib.

Background: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. Methods: To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. Results: Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. Conclusions: Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment.

Celecoxib in Cancer Therapy and Prevention - Review.

BACKGROUND AND OBJECTIVES: It is generally accepted that inflammatory cells found in the tumor microenvironment are involved in the neoplastic process, promoting cell proliferation, survival, and migration. Therefore, administering anti-inflammatory medication in cancer therapy seems to be justified. A potential pathway associated with the aforementioned issue is cyclooxygenase-2 inhibition, particularly as the overexpression of this enzyme has been proven to occur in cancer tissues and is also associated with a poor prognosis in several types of human malignancies. Celecoxib, a COX-2 selective inhibitor, has been utilized for over 20 years, particularly as an anti-inflammatory, analgesic and antipyretic medication. However, to date, its antineoplastic properties have not been sufficiently investigated. In recent years, the number of research studies on the antineoplastic effects of celecoxib has increased considerably. The vast majority of publications refers to preclinical studies attempting to elucidate its mechanisms of action. Clinical trials concerning celecoxib have focused primarily on the treatment of cancers of the colon, breast, lung, prostate, stomach, head and neck, as well as premalignant lesions such as familial adenoma polyposis. In this review article authors attempt to summarise the latest research which has elucidated celecoxib use in the treatment and prevention of cancer. CONCLUSION: Both preclinical and clinical studies have demonstrated promising results of the role of celecoxib in the treatment and prevention of cancer - the best outcome was observed in colon, breast, prostate and head and neck cancers. However, more clinical trials providing real evidence-based clinical advances of celecoxib use are needed.

Peroneal artery-vein index as a potential factor of thrombosis occurrence in free osteocutaneous fibula flap.

BACKGROUND: Despite high popularity and great success rates of free osteocutaneous fibula flaps, the flap failure caused by vascular thrombosis is still a challenging problem. The authors present their evaluation of a potential thrombosis risk factor - a peroneal artery-vein index. METHODS: The authors evaluated the diameters of peroneal vessels and peroneal artery-vein indexes based on the computed tomography angiographies in 10 patients who underwent a mandible reconstruction with a free fibula flap and compared the results with clinical outcome. RESULTS: In one case the flap was lost, because of thrombosis in the donor vein. This patient presented superficial varicose veins of both lower extremities. Peroneal vein diameters in this patient ranged from 5,05 mm to 6,68 mm and were higher than in patients without complications. The peroneal artery-vein index in the patient with thrombosis ranged from 0,37 to 0,50 with median 0,40 and was lower than in patients without complications. CONCLUSIONS: High disproportion between peroneal artery and concomitant veins might be a potential risk factor of the occurrence of venal thrombosis. Detailed perioperative examination of peroneal veins in patients with varicosities should be considered.