Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary glands) that plays a role in tumor-cell biology. The chief components of the CS are the molecular chaperones, some of which belong to families of evolutionarily related molecules named heat shock protein (Hsp). We are quantifying and mapping these molecular chaperones in salivary glands to determine their possible role in the carcinogenetic mechanisms in these glands and to assess their potential as diagnostic biomarkers and therapeutic targets. Here, we report recent findings on Hsp10 and Hsp90 and show that the quantitative and topographic patterns of tissue Hsp90 are distinctive of malignant tumors and differentiate benign from malignant lesions. The Hsp90 results show a correlation between quantity of chaperone and tumor progression, which in turn calls for negative chaperonotherapy, namely, elimination/inhibition of the chaperone to stop the tumor. We found that in vitro, the Hsp90 inhibitor Ganetespib is cytotoxic for the salivary gland UM-HACC-2A cell line. The drug, by interfering with the pro-survival NF-κB pathway, hampers cellular proliferation and migration, and favors apoptosis, and can, therefore, be considered a suitable candidate for future experimentation to develop a treatment for salivary gland tumors.

The chaperone system (CS) is emerging as a key multistage participant in carcinogenesis. The CS chief components are the molecular chaperones (some of which are named heat shock proteins or Hsp), which are typically cytoprotective but if abnormal in structure, location, or quantity, can become etiopathogenic and cause diseases, known as chaperonopathies, including some cancers. For example, abnormal Hsp90 expression is associated with tumorigenesis and poor prognosis. Hsp90 is positioned at the center of several key oncogenic pathways by stabilizing and activating oncogenic kinases responsible for driving cell proliferation and survival. Consequently, inhibition of Hsp90 is being investigated as a possible anti-cancer strategy and some results are encouraging. However, the 5-year survival rate for patients suffering from salivary gland carcinomas is still unsatisfactory. Because of the rarity of these malignancies, they may have been overlooked and understudied and, thus, novel therapies (e.g., inhibition of CS components like Hsp90 and others) are urgently needed. In this review, we also summarize the histopathological quantitative patterns and the intra- and extra-cellular location characteristics of Hsp90 in tumors of salivary glands, pointing to their potential for differential diagnosis, prognostication, and patient monitoring.

Background: Anatomical variations and, in particular, arterial variations constitute an important chapter in the learning of Clinical Anatomy. Purpose: The purpose of this report is to describe a rare bilateral anatomical variation in the internal thoracic artery (ITA) in a 60-year-old corpse and to depict its extreme clinical importance in coronary artery bypass surgery. Methods: The rare bilateral aberrant branches of the internal thoracic artery and their course in the thorax were incidentally discovered during routine anatomy dissection of the thorax at the Faculty of Medicine and Medical Sciences of the University of Balamand. The findings were thoroughly documented using digital photography, and the dissection followed the instructions from the “16th Edition of Grant’s Dissector”. Results: In the observed case, the left aberrant branch of ITA descends laterally and gives medial and lateral anterior intercostal branches at the first six intercostal spaces. Conversely, the right aberrant artery, which branches from the ITA, descends laterally and gives medial and lateral branches to every intercostal space in the first five intercostal spaces. Conclusion: This report emphasizes that any unexpected variations in the lateral aberrant branches of the internal thoracic artery may complicate the surgical procedure. Bilateral aberrant lateral branches of the internal thoracic artery constitute rare anatomical variations of the internal thoracic artery and have been rarely reported in the literature. Such a course for aberrant lateral branches in the thorax poses possible lethal complications during several procedures involving the thorax, including basic coronary artery bypass graft, thoracocentesis and intercostal paracentesis and breast reconstruction.