Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro.

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection. To this end, we subjected the cells to short- and long-term acidic pressure and recovery to pHe 7.4. This treatment aimed at mimicking PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, and epithelial-mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing. Our results indicate that short acidic treatment limits growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, potentiating their metastatic potential when re-exposed to pHe 7.4. The RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We describe an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Our work clearly demonstrates that upon acidosis stress, PDAC cells acquire more invasive cell phenotypes by promoting EMT and thus paving the way for more aggressive cell phenotypes.

Analysis of Cervical Range of Motion in Subjects Affected by Temporomandibular Disorders: A Controlled Study.

Background and Objectives: The aim of this study were to compare the cervical ROM data obtained from accelerometer exams between patients suffering from TMDs (study group) and healthy patients (control group). Material and Methods: A sample of 43 young adult subjects (23 control subjects and 20 TMD patients) were included in this study and analyzed with the accelerometer (Baiobit™, BTS, Garbagnate Milanese, Milan, Italy) to assess cervical ROM using a standardized protocol, including the following occlusal conditions: mandibular rest position, clenching, clenching with cotton rolls, maximal intercuspation, and mandibular position with cotton rolls. The cervical ROM was measured in degrees and expressed as the mean and standard deviation. Results: TMD patients showed a reduced cervical extension compared to control subjects in all the conditions, with statistically significant relevance. Regarding the other movements, the differences were not statistically or clinically significant. Conclusions: Based on the results of the present study, it can be observed that temporomandibular disorders are associated with a decreased cervical extension range, while the remaining components of ROM do not seem to be significantly associated. The use of accelerometers in ROM analysis could be helpful in improving interdisciplinary communication between dentists and physiotherapists.