1,721,014 research outputs found
Prognostic biomarkers in oral squamous cell carcinoma: current evidence and future directions
No full textOral squamous cell carcinoma (OSCC) exhibits significant prognostic heterogeneity. This has prompted extensive research into biomarkers that can predict clinical outcomes beyond conventional staging systems. This mini review summarizes findings from the existing literature to provide a comprehensive examination of the prognostic significance of malignancy and progression factors in OSCC, offering insights into future perspectives. There is clear evidence that molecular and protein-based biomarkers, in addition to established clinical and histopathological features, such as lymph node involvement, extranodal spread, and depth of invasion, strongly correlate with overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Integrating different gene expression signatures, microRNA (miRNA) profiles, and changes in intracellular signaling pathways enables more differentiated risk stratification. Protein biomarkers such as cyclin D1, trophoblast cell surface antigen 2 (TROP2), urokinase-type plasminogen activator receptor (uPAR), and E-cadherin have been shown to provide clinically useful prognostic information. These results underscore the importance of incorporating biomarkers into individualized risk stratification to enhance personalized treatment regimens and outcomes for OSCC patients. Currently, however, established clinical and histopathological parameters, as well as a limited number of validated molecular profiles, remain the most reliable prognostic indicators. While identifying new biomarkers is promising, establishing standardized protocols and implementing careful prospective validation are essential to ensuring their seamless integration into standard clinical practice.Open-Access-Publikationsfonds 202
Epigenetic modification suppresses proliferation, migration and invasion of urothelial cancer cell lines
No full textEpigenetic approaches offer additional therapeutic options, including apoptosis induction, modification of cell cycle regulating proteins and the re-expression of pharmaceutical targets, such as hormone receptors. The present study analyzed the effect of the epigenetic modifiers 5-aza-2'-deoxycytidine and Trichostatin A on the proliferative, migratory and invasive behavior of four urinary bladder cancer cell lines (RT-4, RT-112, VMCUB-1 and T-24), and the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Cell proliferation, migration and invasion assays revealed that treatment with the two epigenetic modifiers resulted in proliferation inhibition in all cell lines, and migration and invasion inhibition in RT-4, RT-112 and T-24 cell lines. Quantitative polymerase chain reaction demonstrated that the mRNA expression of a broad selection of MMPs and their TIMPs was induced in all cell lines, and MMP-14 mRNA expression was suppressed in all cell lines, with the exception of RT-4. In conclusion, epigenetic modifications suppressed the motility and invasiveness of three out of four urothelial cancer cell lines. The inhibitory effect on cell motility appears to be crucial for reduced invasive properties. However, even a broad spectrum of mRNA analysis does not sufficiently explain the loss of invasiveness, as it does not allow for functional conclusions. Further complex urothelial tumour models should be applied to investigate whether epigenetic therapeutic approaches may be an option in urothelial cancer
Perioperative laboratory profiles predict complications after extensive head and neck reconstruction: A proof-of-concept study
No full textThis dataset comprises the retrospective analysis of perioperative laboratory parameters from 233 patients with oral squamous cell carcinoma (OSCC) who underwent tumor resection and reconstructive head and neck surgery, including detailed laboratory histories, complication rates, and clinical parameters for the investigation of predictive markers of postoperative complications
Implementation and Validation of a 24/7 System for the Monitoring of Antiepileptic Drugs
No full textComplete dataset on the implementation and validation of a 24/7 therapeutic drug monitoring (TDM) system for 26 antiepileptic drugs (AEDs)
Membrane connexin 43 acts as an independent prognostic marker in oral squamous cell carcinoma
No full textThe aim of the present study was to evaluate the expression and localization of connexin (Cx) 26, -43 and -45 in a group of 35 patients with primary oral squamous cell carcinoma (OSCC) with the objective of making a more accurate disease prognosis. We analysed the expression of connexins in tissue samples of primary OSCC, matching oral mucosa free of dysplasia, and its associated lymph node metastases (LNM) by semi-quantitative immunohistochemistry of membrane, cytoplasmic and nuclear connexin expression. The levels of expression were correlated with the overall survival time (OS). Cx43 was overexpressed in tumour cells compared to epithelia in dysplasia-free mucosa. High membrane expression of Cx43 on tumour cells was the only statistically significant and independent prognostic factor of short OS (P=0.0088). Membrane expression of Cx43 in matching dysplasia-free mucosa acted similarly, but did not reach statistical significance (P=0.059). No correlation was found between the Cx26, Cx45 expression and OS. We conclude that Cx43 expression in dysplasia-free mucosa may indicate a very early stage of tumour promotion. Although overexpression of Cx43 is found in invasive tumours we only found membrane Cx43 expression to correlate with OS. This observation suggests that cytoplasmic Cx43 serves as storage and only membrane translocation may promote the formation of gap junctions and gap junctional intercellular communication (GJIC) with prognostic relevance
The Anti-EMMPRIN Monoclonal Antibody hMR18-mAb Induces Tumor Dormancy and Inhibits the EMT Process in Human Carcinoma Cell Lines Co-Cultured with Macrophages
No full textBackground: The epithelial-to-mesenchymal transition (EMT) process is necessary for metastasis as it enables tumor cells’ migration and invasion. In the remote organ, tumor cells can develop into metastatic lesions or arrest their proliferation and become dormant, thus suspending metastatic development. EMMPRIN is a membrane glycoprotein, implicated in cell–cell interactions, proliferation, angiogenesis, and EMT. We asked whether neutralizing EMMPRIN with the new anti-EMMPRIN monoclonal antibody hMR18-mAb can inhibit EMT. Methods: We co-cultured tumor cell lines (breast carcinoma MCF-7, MDA-MB-231, or oral squamous cell carcinoma SCC-40) together with U937 monocytic-like cells, with or without hMR18-mAb or its negative control rabbit IgG. Results: We demonstrate that depending on the initial state of the cells along the epithelial–mesenchymal axis (E/M axis), co-culture enhanced the EMT process, whereas hMR18-mAb reversed this effect. The co-culture increased EMT-inducer cytokines in all cell lines (by 2.5-fold), while hMR18-mAb reduced them (by ~55–70% in the breast cancer cells and by 81% in the SCC-40 cells). The co-culture reduced E-cadherin (by 2-fold in MCF-7 and SCC-40 cells) and increased vimentin expression (by 2–3-fold in MDA-MB-231 and SCC-40), while hMR18-mAb reverted this effect. Co-culture enhanced proliferation, migration, and angiogenic potential of the tumor cells, while hMR18-mAb reduced these by ~20%, 30–44% and ~60–80%, respectively. Co-culture reduced the standard markers of dormancy (NR2F1, p21, p27) and stemness (SOX2, Nanog) (by 30–60% in MCF-7 and SCC-40), while hMR18-mAb elevated gene expression of these markers (by 1.5–3.5-fold) in all cell lines, pushing the cells towards dormancy. Conclusions: We conclude that EMMPRIN is a gatekeeper that prevents cells from entering dormancy, and that hMR18-mAb disrupts this effect. As it is the first antibody shown to induce dormancy in tumor cells and stop the development of metastases, this could become a new therapeutic strategy to prevent and treat metastasis
EMMPRIN promotes spheroid organization and metastatic formation: comparison between monolayers and spheroids of CT26 colon carcinoma cells
No full textBackground In vitro studies often use two-dimensional (2D) monolayers, but 3D cell organization, such as in spheroids, better mimics the complexity of solid tumors. To metastasize, cancer cells undergo the process of epithelial-to-mesenchymal transition (EMT) to become more invasive and pro-angiogenic, with expression of both epithelial and mesenchymal markers. Aims We asked whether EMMPRIN/CD147 contributes to the formation of the 3D spheroid structure, and whether spheroids, which are often used to study proliferation and drug resistance, could better model the EMT process and the metastatic properties of cells, and improve our understanding of the role of EMMPRIN in them. Methods We used the parental mouse CT26 colon carcinoma (CT26-WT) cells, and infected them with a lentivirus vector to knock down EMMPRIN expression (CT26-KD cells), or with an empty lentivirus vector (CT26-NC) that served as a negative control. In some cases, we repeated the experiments with the 4T1 or LLC cell lines. We compared the magnitude of change between CT26-KD and CT26-WT/NC cells in different metastatic properties in cells seeded as monolayers or as spheroids formed by the scaffold-free liquid overlay method. Results We show that reduced EMMPRIN expression changed the morphology of cells and their spatial organization in both 2D and 3D models. The 3D models more clearly demonstrated how reduced EMMPRIN expression inhibited proliferation and the angiogenic potential, while it enhanced drug resistance, invasiveness, and EMT status, and moreover it enhanced cell dormancy and prevented CT26-KD cells from forming metastatic-like lesions when seeded on basement membrane extract (BME). Most interestingly, this approach enabled us to identify that EMMPRIN and miR-146a-5p form a negative feedback loop, thus identifying a key mechanism for EMMPRIN activities. These results underline EMMPRIN role as a gatekeeper that prevents dormancy, and suggest that EMMPRIN links EMT characteristics to the process of spheroid formation. Conclusions Thus, 3D models can help identify mechanisms by which EMMPRIN facilitates tumor and metastasis progression, which might render EMMPRIN as a promising target for anti-metastatic tumor therapy
Correction to: Force delivery modification of removable thermoplastic appliances using Hilliard precision thermopliers for tipping an upper central incisor
No full textForce delivery modification of removable thermoplastic appliances using Hilliard precision thermopliers for tipping an upper central incisor
No full textOBJECTIVES: To evaluate the force delivered by removable thermoplastic appliances (RTAs, aligners), altered with Hilliard precision thermopliers, on an upper central incisor to tip it in the palatal and vestibular directions. MATERIALS AND METHODS: A total of 10 aligners made from Ideal Clear® (polyethylene terephthalate glycol copolyester, PET-G) with a thickness of 1 mm were used in force analysis. Different-sized spot-thermoformed protuberances (bumps) were generated by activating the thermoplier (thin and thick) up to 30°, 60° and 90° in the centre of the palatal and vestibular surfaces of the aligner in 15° steps. The tipping (Fx) and intrusive (Fz) force components were measured on the isolated upper central incisor as part of a standardized resin model, with or without vertical loading by a weight equivalent. RESULTS: Thermoplier activation at 30°, 60° and 90° resulted in different bump heights. The analysis revealed significantly higher Fx and Fz values with increasing bump heights for every activation step in all cases (p < 0.0001, respectively). Overall, the values of the Fx force component were higher than those observed for Fz. Significant differences between the palatal and vestibular tipping procedures were found depending on the resulting force components when the thin thermoplier was used; in contrast, the thick thermoplier resulted in a larger dispersion of the force magnitudes. CONCLUSIONS: Aligners modified with Hilliard precision thermopliers showed altered biomechanical parameters. This approach could be an option for treatment modification. CLINICAL RELEVANCE: The instrumental examination provided informative results for daily practice, as activation, force dosage and different force values under chewing pressure can be estimated more precisely based on the determined force levels
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