Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro

Investigations of the mechanisms of the cancer-preventive activity of apigenin (4',5,7,-trihydroxyflavone), a plant-derived, anti-carcinogenic flavonoid, showed its interference with cell proliferation, survival, and gap junctional coupling. We used a model based on non-invasive HeLa wild-type cells and their connexin43 (Cx43) transfected counterparts to correlate the effect of apigenin on tumour cell invasiveness with its influence on cell motility. Both cell lines displayed similar motile properties in control conditions. Apigenin treatment resulted in a significant and reversible inhibition of translocation of both HeLa wild-type cells and HeLa Cx43 transfectants. The effect of apigenin on cell proliferation was less pronounced especially at low apigenin concentration, whereas its influence on cell motility correlated with the reduction of the invasive potential of HeLa Cx43 cells as shown by an invasion assay based on the confrontation of tumour cell spheroids with chick embryo heart fragments. HeLa Cx43 cells were highly invasive in controls, but did not invade the heart tissue at tumour cell aggregate-fibroblast capsule interfaces in the presence of apigenin and failed to fully engulf these heart fragments. Because the motility of chick heart fibroblasts was only slightly affected by apigenin, these observations indicate that apigenin exerts its anti-invasive effect on HeLa cells predominantly via a specific inhibition of tumour cell motility. This inhibitory effect of apigenin on tumour cell invasiveness in vitro demonstrates that apigenin may exert its anti-tumorigenic effect in vivo via inhibition of tumour cell penetration of the healthy tissue.     

Stricture caused by a plastic vascular clip used during an operation of minimally invasive esophagectomy

This article describes the case of a 62-year-old female who had had minimally invasive esophagectomy (Ivor-Lewis) for squamous cell carcinoma of the distal third of the esophagus. The anastomotic stenosis was accompanied by solid food dysphagia and the presence of a foreign body in the esophagus. The foreign body was fixed to the esophageal wall and could not be removed endoscopically. The patient was reoperated on through a 8?cm right thoracotomy. The anastomosis was reached via a gastrotomy, and the large-size plastic vascular clip was removed. The clip was primarily used to close the transsected azygos vein, it was then incorporated into the esophageal anastomotic region and subsequently partially protruded into the lumen of the gastrointestinal tract. After removal of the clip, backward dilatation of the anastomosis was performed by Savary-Gilliard dilators, with restoration of its proper diameter.     

Molecular activity of sirolimus and its possible application in tuberous sclerosis treatment

Sirolimus is one of the intensively investigated drugs with pluripotent activities. It binds to its intracellular receptor FKBP12 (FK506-binding protein 12), a member of the family of FK506-binding proteins, and inhibits the activity of mTOR, a serine/threonine kinase involved in numerous cell processes linked to cell growth control. The drug is currently registered for the prophylaxis of organ rejection and for use in coronary stents. However, unique characteristics of sirolimus make it a good candidate for anti-cancer therapy. Indeed, phase II and III clinical studies in humans with several types of neoplasms are already under way. The review describes molecular activity of sirolimus and its analogs, characteristic for specific applications, in view of very recent advances involving tuberous sclerosis complex (TSC)-mediated signaling pathways. Current studies with sirolimus performed in tuberous sclerosis animal models are presented. Possible application of sirolimus for treating tuberous sclerosis, disease caused by mutations of TSC proteins, is discussed.