ABSTRACT
It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.
ABSTRACT
<p><b>OBJECTIVE</b>To study the anatomy of supraclavicular artery island flap and report the clinical application of the island flap for the reconstruction of tongue defects.</p><p><b>METHODS</b>The branch, origination, course, length and diameter of transverse cervical artery and supraclavicular artery were observed on 20 flaps of 10 adult cadavers perfused with lead oxide-gel, and the draining veins were also observed. The supraclavicular artery island flaps were used to reconstruct the defects following tongue cancer ablation in 4 patients, and the data concerning functional impairment, aesthetic outcome and donor site morbidity were analyzed.</p><p><b>RESULTS</b>The transverse cervical artery were originated from the thyrocervical trunk or subclavical artery, and separated into deep branch and superficial branch above the middle third of the clavicle. The supraclavicular artery were originated from superficial branch of the transverse cervical artery and extended to backward and outward, and run over surface of trapezius, acromial end of clavicle and deltoid fascia, and then penetrated the deep fascia and go into skin and subcutaneous tissue of supraclavicular and shoulder regions. The distance between the origins of the supraclavicular and transverse cervical arteries was on average 4.3 cm, and the distance between the origin of supraclavicular artery and the point where it penetrated the deep fascia was on average 3.6 cm. The external diameter of the transverse cervical artery was on average 2.7 mm, and the external diameter of supraclavicular artery was on average 1.1 mm. Two supraclavicular comitant veins ran adjacent to the supraclavicular artery and drained into the transverse cervical vein and external jugular vein respectively. In the clinical study, 3 flaps survived completely and part of the skin paddle of the flap in one case exhibited necrosis. The contour and function of tongues were restored well and there was no limitation of shoulder motion in all 4 cases.</p><p><b>CONCLUSIONS</b>The supraclavicular artery island flap with supraclavicular artery as nutrient vessel is reliable for reconstruction of oral, maxillofacial and neck defects, and it can be used as a free flap equipped with the transverse cervical artery.</p>