Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a paradoxical effect associated with bone-modifying agents (BMAs) and other drugs. Currently, no valuable diagnostic or prognosis biomarkers exist. The goal of this research was to study MRONJ-related salivary proteome. MATERIALS AND METHODS: This case-control aimed to study salivary proteome in MRONJ versus control groups (i) formed from BMAs consumers and (ii) healthy individuals to unravel biomarkers. Thirty-eight samples of unstimulated whole saliva (18 MRONJ patients, 10 BMA consumers, and 10 healthy controls) were collected. Proteomic analysis by SWATH-MS coupled with bioinformatics analysis was executed. RESULTS: A total of 586 proteins were identified, 175 proteins showed significant differences among MRONJ versus controls. SWATH-MS revealed differentially expressed proteins among three groups, which have never been isolated. These proteins had distinct roles including cell envelope organization, positive regulation of vesicle fusion, positive regulation of receptor binding, or regulation of low-density lipoprotein particle clearance. Integrative analysis prioritized 3 proteins (MMP9, AACT, and HBD). Under receiver-operating characteristic analysis, this panel discriminated MRONJ with a sensitivity of 90% and a specificity of 78.9%. CONCLUSION: These findings may inform a novel biomarker panel for MRONJ prediction or diagnosis. Nonetheless, further research is needed to validate this panel.

Impact of abutment geometry on early implant marginal bone loss. A double-blind, randomized, 6-month clinical trial.

OBJECTIVES: The objective of this study was to analyze the impact of the abutment width on early marginal bone loss (MBL). MATERIAL AND METHODS: A balanced, randomized, double-blind clinical trial with two parallel experimental arms was conducted without a control group. The arms were "cylindrical" abutment and "concave" abutment. Eighty hexagonal internal connection implants, each with a diameter of 4 × 10 mm, were placed in healed mature bone. The main variable was the peri-implant tissue stability, which was measured as MBL at 8 weeks and 6 months. RESULTS: The final sample consisted of 77 implants that were placed in 25 patients. 38 (49.4%) were placed using the cylindrical abutment, and the other 39 (50.6%) were placed using the concave abutment. The early global MBL of -0.6 ± 0.7 mm in the cylindrical abutment group was significantly higher than it was in the concave abutment group, in which the early global MBL was -0.4 ± 0.6 mm (p = .030). The estimated effect size (ES) was negative for the cylindrical abutment (ES = -1.3730, CI -2.5919 to -0.1327; t-value = -2.4893; p = .0139), therefore implying a loss of mean bone level, and it was positive for the concave abutment (ES = 2.8231; CI: 1.4379 to 4.2083; t-value = 4.0957; p = .0002), therefore implying an increase in the average bone level. CONCLUSIONS: The concave abutments presented significantly less early MBL at 6 months post-loading than classical cylindrical abutments did.

Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.