ABSTRACT
In the last decade, a group of Ca2+ channels called Piezo were discovered, demonstrating a decisive role in the cellular response to mechanical stimuli and being essential in the biological behavior of cells regarding the extracellular compartment. Several investigations have suggested a potential role in carcinogenesis, with a tumor suppressor role in some cases but increased expression in several high-grade neoplasms. Regarding Piezo2 expression in mammary gland neoplasms, a protective role for Piezo2 was initially suggested, but a subsequent study demonstrated a relationship between Piezo2 expression and the highly aggressive triple-negative phenotype of breast carcinoma. A cohort of 125 patients with clinical follow-up was chosen to study Piezo2 expression and clarify its clinical implications using the same immunohistochemical evaluation performed for other breast carcinoma parameters. Fisher's exact test was chosen to identify potential relationships between the different variables. A significant association was found with the Ki67 proliferation index, but not with mitoses. The tendency of most proliferative tumors was to have an increased score for Piezo2. A similar association was found between Piezo2 expression and perineural invasion.
ABSTRACT
As an essential component of mechano-gated ion channels, critically required for mechanotransduction in mammalian cells, PIEZO2 is known to be characteristically expressed by Merkel cells in human skin. Here, we immunohistochemically investigated the occurrence of Piezo channels in a case series of Merkel cell carcinoma. A panel of antibodies was used to characterize Merkel cells, and to detect PIEZO2 expression. All analyzed tumors displayed PIEZO2 in nearly all cells, showing two patterns of immunostaining: membranous and perinuclear dot-like. PIEZO2 co-localized with cytokeratin 20, chromogranin A, synaptophysin and neurofilament. Moreover, neurofilament immunoreactive structures resembling nerve-Merkel cell contacts were occasionally found. PIEZO2 was also detected in cells of the sweat ducts. The role of PIEZO2 in Merkel cell carcinoma is still unknown, but it could be related with the mechanical regulation of the tumor biology or be a mere vestige of the Merkel cell derivation.
ABSTRACT
Transdermal delivery can be accomplished through various mechanisms including formulation optimization, epidermal stratum corneum barrier disruption, or directly by removing the stratum corneum layer. Microneedling, electroporation, a combination of both and also the intradermal injection known as mesotherapy have proved efficacy in epidermal-barrier disruption. Here we analyzed the effects of these methods of epidermal-barrier disruption in the structure of the skin and the absorption of four compounds with different characteristics and properties (ketoprofen, biotin, caffein, and procaine). Swine skin (Pietrain x Durox) was used as a human analogue, both having similar structure and pharmacological release. They were biopsied at different intervals, up to 2 weeks after application. High-pressure liquid chromatography and brightfield microscopy were performed, conducting a biometric analysis and measuring histological structure and vascular status. The performed experiments led to different results in the function of the studied molecules: ketoprofen and biotin had the best concentrations with intradermal injections, while delivery methods for obtaining procaine and caffein maximum concentrations changed on the basis of the lapsed time. The studied techniques did not produce significant histological alterations after their application, except for an observed increase in Langerhans cells and melanocytes after applying electroporation, and an epidermal thinning after using microneedles, with variable results regarding dermal thickness. Although all the studied barrier disruptors can accomplish transdermal delivery, the best disruptor is dependent on the particular molecule.
ABSTRACT
Proliferating trichilemmal tumours (PTT) are defined by a benign squamous cell proliferation inside a trichilemmal cystic (TC) cavity. A possible explanation of this proliferative phenomenon within the cyst may be molecular alterations in genes associated to cell proliferation, which can be induced by ultraviolet radiation. Among other genes, alterations on TP53 and DNA mismatch repair proteins (MMR) may be involved in the cellular proliferation observed in PTT. Based on this assumption, but also taking into account the close relationship between the sebaceous ducts and the external root sheath where TC develop, a MMR, a p53 expression assessment and a TP53 study were performed in a series of 5 PTT cases, including a giant one. We failed to demonstrate a MMR disorder on studied PTT, but we agree with previous results suggesting increased p53 expression in these tumours, particularly in proliferative areas. TP53 alteration was confirmed with FISH technique, demonstrating TP53 deletion in most cells.
ABSTRACT
PURPOSE: To describe the diagnosis and management of Coats disease in a patient with Fanconi anemia. METHODS: Case report. RESULTS: A 12-year-old girl with Fanconi anemia developed Coats disease. Retinal vasculature anomalies are present in both diseases; however, differential diagnosis in this case could be based on the presence of telangiectasias, which are typical of Coats disease, and the absence of perivascular sheathing, usually described in the uncommon retinal manifestations of Fanconi anemia. The stage 4 Coats disease was managed with intravitreal bevacizumab injections and later pars plana vitrectomy with silicone oil tamponade surgery, which prevented enucleation despite visual loss. CONCLUSIONS: Patients with Fanconi anemia can have retinal vasculature anomalies that are not necessarily related to this systemic anomaly. In this case, the retinal alterations were related to advanced Coats disease stage, which was successfully treated, and enucleation of the affected eye was not necessary.
