RESUMEN
Background: The nasal ala has always been considered a difficult anatomical structure to restore, particularly when full-thickness reconstruction is needed. Although the forehead flap is considered the flap of choice, the nasolabial turnover flap, despite being a one-step surgical procedure, has been largely ignored for nasal ala reconstruction. We present our experience performing nasal ala full-thickness reconstruction with the nasolabial turnover flap, reporting on its advantages and comparing it with the most commonly used alternative techniques. Methods: Between 2017 and 2022, 48 patients presenting full-thickness defects of the nasal ala after skin cancer resection underwent reconstruction with a nasolabial turnover flap at two large regional plastic surgery units. Surgical technique was presented in detail, with particular attention in describing the complex three-dimensional movement of the flap. Results: All patients healed uneventfully, with good functional and cosmetic outcomes. No major complications were observed. Conclusions: The nasolabial turnover flap is a reliable and valuable option for achieving full-thickness nasal ala reconstruction. Satisfactory results in terms of function and cosmetic appearance can be obtained in a one-stage operation. Based upon our experience, the nasal turnover flap could be considered a viable reconstruction option, even for less-experienced surgeons.
RESUMEN
The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy.