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An important determinant for oral squamous cell carcinoma (OSCC) onset and outcome is the composition of the tumor microenvironment (TME). Thus, the study of the interactions occurring among cancer cells, immune cells, and cancer-associated fibroblasts within the TME could facilitate the understanding of the mechanisms underlying OSCC development and progression, as well as of its sensitivity or resistance to the therapy. In this context, it must be highlighted that the characterization of TME proteins is enabled by proteomic methodologies, particularly mass spectrometry (MS). Aiming to identify TME protein markers employable for diagnosing and prognosticating OSCC, we have retrieved a total of 119 articles spanning 2001 to 2023, of which 17 have passed the selection process, satisfying all its criteria. We have found a total of 570 proteins detected by MS-based proteomics in the TME of OSCC; among them, 542 are identified by a single study, while 28 are cited by two or more studies. These 28 proteins participate in extracellular matrix remodeling and/or energy metabolism. Here, we propose them as markers that could be used to characterize the TME of OSCC for diagnostic/prognostic purposes. Noteworthy, most of the 28 individuated proteins share one feature: being modulated by the hypoxia that is present in the proliferating OSCC mass.

High levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2 and angiopoietin (ANG)-2 are found in tissues from oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). As might be expected, VEGF, FGF-2, and ANG-2 overexpression parallels the development of new blood and lymphatic vessels that nourish the growing OPMDs or OSCCs and provide the latter with metastatic routes. Notably, VEGF, FGF-2, and ANG-2 are also linked to the epithelial-to-mesenchymal transition (EMT), a trans-differentiation process that respectively promotes or exasperates the invasiveness of normal and neoplastic oral epithelial cells. Here, we have summarized published work regarding the impact that the interplay among VEGF, FGF-2, ANG-2, vessel generation, and EMT has on oral carcinogenesis. Results from the reviewed studies indicate that VEGF, FGF-2, and ANG-2 spark either protein kinase B (AKT) or mitogen-activated protein kinases (MAPK), two signaling pathways that can promote both EMT and new vessels' formation in OPMDs and OSCCs. Since EMT and vessel generation are key to the onset and progression of OSCC, as well as to its radio- and chemo-resistance, these data encourage including AKT or MAPK inhibitors and/or antiangiogenic drugs in the treatment of this malignancy., Competing Interests: The authors declare no conflicts of interest.

Oral squamous cell carcinoma (OSCC) is a rapidly progressive cancer that often develops resistance against DNA damage inducers, such as radiotherapy and chemotherapy, which are still the standard of care regimens for this tumor. Thus, the identification of biomarkers capable of monitoring the clinical progression of OSCC and its responsiveness to therapy is strongly required. To meet this need, here we have employed Whole Genome Sequencing and RNA-seq data from a cohort of 316 patients retrieved from the TCGA Pan-Cancer Atlas to analyze the genomic and transcriptomic status of the DNA damage response (DDR) genes in OSCC. Then, we correlated the transcriptomic data with the clinical parameters of each patient. Finally, we relied on transcriptomic and drug sensitivity data from the CTRP v2 portal, performing Pearson's correlation analysis to identify putative vulnerabilities of OSCC cell lines correlated with DDR gene expression. Our results indicate that several DDR genes show a high frequency of genomic and transcriptomic alterations and that the expression of some of them correlates with OSCC grading and infection by the human papilloma virus. In addition, we have identified a signature of eight DDR genes (namely CCNB1 , CCNB2 , CDK2 , CDK4 , CHECK1 , E2F1 , FANCD2 , and PRKDC ) that could be predictive for OSCC response to the novel antitumor compounds sorafenib and tipifarnib-P1. Altogether, our data demonstrate that alterations in DDR genes could have an impact on the biology of OSCC. Moreover, here we propose a DDR gene signature whose expression could be predictive of OSCC responsiveness to therapy.

Aim : The aim of the present study was to investigate quantitative histological examination of bone reconstructed with non-resorbable high-density polytetrafluoroethylene membrane (d-PTFE), left intentionally exposed in post extraction sockets grafted with anorganic bone material, and removed after four weeks, versus extraction and guided bone regeneration (GBR), performed two months later. Materials and Methods : This study was designed as a multicenter randomized controlled trial of parallel-group design. Patients were selected and consecutively treated in three centers in Italy. Patients randomly received intentionally exposed non-resorbable d-PTFE membrane (group A), or guided bone regeneration (group B), to treat post-extractive alveolar bone defects with implant-supported restorations. Outcomes were: the implant failure, any mechanical and biological complications, patient satisfaction, and qualitative and histomorphometric evaluation of the collected bone samples. Results : Eighteen patients were consecutively enrolled in the trial. Of these, six out of 18 patients were male. All the included patients were treated according to the allocated interventions, and no drop out occurred. No implant failure and no complications were experienced, and all the patients were fully satisfied with the function and aesthetic of their implant-supported restoration, without difference between groups. Morphological analysis revealed no sign of tissue reaction, such as fibrosis or necrosis. Regenerated bone was well mineralized in both groups, but it seemed more mature in group B than in group A. Three samples showed a minimal number of lymphocytes. Several blood vessels of small size occupied the medullary spaces, where the tissue resulted in more maturity, indicating the activity of the tissue in progress. The histomorphometric evaluation showed no statistically significant differences in the tissue volume fractions between the two groups of patients. Conclusions : With the limitation of the present study, buccal plate reconstruction with an intentionally exposed non-resorbable membrane is an effective and easy procedure for regenerating a resorbed buccal bone plate, reducing the need for guided bone regeneration.

Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.

To evaluate the implant and prosthetic of two implants with different surfaces and neck design. Enrolled patients received bone level, 12° conical connection implants (Nobel Parallel, Nobel Biocare; NOBEL group) with anodized surface (TiUnite) and roughness of 1.35 μm, or transmucosal implant system (Prama, Sweden and Martina; PRAMA group) with convergent collar, ZIrTi surface, and roughness 1.4-1.7 μm. Both implants were made of pure grade IV titanium, with similar diameter and length, chosen according to the dentistry department availability and patient's request. After early prosthesis delivery, patients were filled for at least one year. Outcome measures were: implant and prosthetic survival and success rates, physiological marginal bone remodeling, periodontal parameters and pink esthetic score (PES). Results: Fifteen patients were allocated and treated in each group. At the one-year follow-up, three patients dropped out, one in the NOBEL group and two in the PRAMA group. During the entire time of investigation, all implants survived and the prostheses were successful. No statistically significant differences were found in term of marginal bone loss, periodontal parameters, and aesthetics ( p > 0.05). Conclusion: With the limitations of the present study, both implant systems showed successful clinical results. Finally, many other clinical and surgical variables may influenced marginal bone levels, implant survival, and periodontal parameters. More homogenous clinical trials with larger samples are needed to confirm these preliminary conclusions.

Background: The aim of the present prospective case series study was to evaluate the implant and prosthetic survival rates, complications and marginal bone loss using ultra-fine titanium mesh membrane with simultaneous implant placement, to provide space maintenance mandatory for guided bone reconstruction of alveolar bone defects., Materials and Methods: patients were recruited and treated at a private clinic in Rome, Italy, between March 2016 and October 2017. Self-tapping tapered implants were placed through a computer-guided template-assisted approach. Autogenous bone was placed alone over the exposed implant surface, then mixed with inorganic bovine bone material. Finally, the membrane was connected and shaped in order to securely enclose the graft area, and the healing cap was connected and screwed onto the height connector. Outcome measures were: implant and prosthetic failure, biological and mechanical complications, marginal and volumetric bone level changes, esthetic evaluation performed according to the pink aesthetic score (PES)., Results: in total, seven patients (five women, two men) with a mean age of 52.7 ± 20.3 years (range: 27-71) received 10 self-tapping tapered implants and simultaneous guided bone regeneration with ultra-fine titanium mesh membranes. No implants and no prostheses failed during the entire follow-up period. One slightly membrane exposure was observed one month after implant placement in one patient. The mean marginal bone loss (MBL) at implant loading was 0.13 ± 0.09 mm (95 % CI 0.08-0.19). At the 18-month follow-up examination, the mean MBL was 0.28 ± 0.33 mm (95 % CI 0.07-0.50) The difference was not statistically significant (0.15 ± 0.31; 95% CI 0.05-0.35; P = 0.1888). The mean horizontal alveolar ridge width was 3.72 ± 1.08 mm (95% CI 3.22-4.22 mm). At the II-stage surgery, the mean bone width was 8.79 ± 0.98 mm (95% CI 8.51-9.07 mm). The mean bone gain was 5.06 ± 1.13 mm (95% CI 4.68-5.44 mm; P = 0.000). The mean volume of the grafted bone calculated using the superimposition technique was 0.99 ± 0.38 CC (95% CI 0.75-1.23 CC). The mean PES at implant loading was 8.2 ± 0.8 mm (95 % CI 7.7-8.7). At the 18-month follow-up examination, the mean PES was 12.0 ± 0.7 mm (95 % CI 11.5-12.5) The difference was statistically significant (3.8 ± 0.4; 95 % CI 3.5-4.1; P = 0.0000); Conclusion: with the limitation of the present prospective study, the guided bone reconstruction using an ultra-fine titanium mesh membrane with simultaneous implant placement seems to provide good and stable results in implant/prosthesis success. Further research with a longer follow-up and a higher sample size are needed to confirm the results from this preliminary report., Competing Interests: The authors declare no conflict of interest.