Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression. To date, PD-L1 has been widely used as a predictor of the response to ICIs; however, many patients do not benefit from the addition of immunotherapy. Therefore, PD-L1 is not a reliable predictive biomarker of the response, and its accuracy remains controversial due to the lack of a consensus about the assay, the antibody, and the scoring system to adopt, as well as the spatial and temporal heterogeneity of the PD-L1 status. In the precision medicine era, there is an urgent need to identify more sensitive biomarkers in the BC immune oncology field other than just PD-L1 expression. Through the characterization of the tumor microenvironment (TME), the analysis of peripheral blood and the evaluation of immune gene signatures, novel potential biomarkers have been explored, such as the Tumor Mutational Burden (TMB), Microsatellite Instability/Mismatch Repair Deficiency (MSI/dMMR) status, genomic and epigenomic alterations and tumor-infiltrating lymphocytes (TILs). This review aims to summarize the recent knowledge on BC immunograms and on the biomarkers proposed to support ICI-based therapy in TNBC, as well as to provide an overview of the potential strategies to enhance the immune response in order to overcome the mechanisms of resistance.

Characteristics, Biological Properties and Analytical Methods of Trans-Resveratrol: A Review.

Trans-resveratrol (TR) is the biological active isomer of resveratrol and the one responsible for therapeutic effects; both molecules are non-flavonoid phenolics of the stilbenes class found mainly in berries and red grapes. TR biological properties lie in modulation of various enzymatic classes. It is a promising candidate to novel drugs due its applications in pharmaceutical and cosmetic industries, such as anticarcinogenic, antidiabetic, antiacne, antioxidant, anti-inflammatory, neuroprotective, and photoprotector agent. It has effects on bone metabolism, gastrointestinal tract, eyes, kidneys, and in obesity treatment as well. Nevertheless, its low solubility in water and other polar solvents may be a hindrance to its therapeutic effects. Various strategies been developed to overcome these issues, such as the drug delivery systems. The present study performed a research about methods to identify TR and RESV in several samples (raw materials, wines, food supplements, drug delivery systems, and blood plasma). Most of the studies tend to analyze TR and RESV by high performance liquid chromatography (HPLC) coupled with different detectors, even so, there are reports of the use of capillary electrophoresis, electron spin resonance, gas chromatography, near-infrared luminescence, UV-Vis spectrophotometer, and vibrational spectrophotometry, for this purpose. Thus, the review evaluates the biological activity of TR and demonstrates the currently used analytical methods for its quantification in different matrices.

Clinical Relevance of Bone Density Values from CT Related to Dental Implant Stability: A Retrospective Study.

PURPOSE: The majority of the techniques used to assess the primary implant stability are subjective and empirical and can be used during or after the surgery. The aim of this study is to evaluate the bone density prior to surgery, in order to give recommendations to the clinician about the best surgical technique and the type of implant which is needed. MATERIALS AND METHODS: A surgeon operated on 75 patients for 269 implants over the period 2010-2014. He required a CT to plan the surgery and he documented the type, the diameters, and the lengths of the implants, the insertion torque, and the ISQ values. At a later stage another clinician measured bone density and cortical thickness. We endeavoured to get the most accurate superimposition between the implants placed by the surgeon and those placed by the clinician. RESULTS: In maxilla ISQ showed a significant positive correlation with HU values detected for coronal-buccal (r = 0.302; p = 0.020) and middle-lingual (r = 0.295; p = 0.023). Torque showed a positive correlation with cortical bone thickness at the middle of the ridge (ρ = 0.196; p = 0.032). CONCLUSION: It is important to take into consideration the Hounsfield Units and the cortical thickness as predictive parameters during the preoperative assessment, with regard to the choice of the implant type as well as the surgical technique.

Computer guided implantology accuracy and complications.

The computer-based method allows the computerized planning of a surgical implantology procedure, using computed tomography (CT) of the maxillary bones and prosthesis. This procedure, however, is not error-free, unless the operator has been well trained and strictly follows the protocol. A 70-year-old woman whom was edentulous asked for a lower jaw implant-supported prosthesis. A computer-guided surgery was planned with an immediate loading according to the NobelGuide technique. However, prior to surgery, new dentures were constructed to adjust the vertical dimension. An interim screwed metal-resin prosthesis was delivered just after the surgery; however, after only two weeks, it was removed because of a complication. Finally, a screwed implant bridge was delivered. The computer guided surgery is a useful procedure when based on an accurate 3D CT-based image data and an implant planning software which minimizes errors.