Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors:

Our view of cancer biology radically shifted from a "cancer-cell-centric" vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved

Tips and tricks for the surface engineering of well‐ordered morphologically driven silver‐based nanomaterials

Particularly-shaped silver nanostructures are successfully applied in many scientific fields, such as nanotechnology, catalysis, (nano)engineering, optoelectronics, and sensing. In recent years, the production of shape-controlled silver-based nanostructures and the knowledge around this topic has grown significantly. Hence, on the basis of the most recent results reported in the literature, a critical analysis around the driving forces behind the synthesis of such nanostructures are proposed herein, pointing out the important role of surface regulating agents in driving crystalline growth by favoring (or opposing) development along specific directions. Additionally, growth mechanisms of the different morphologies considered here are discussed in depth, and critical points highlighte

Deciphering the loop of epithelial-mesenchymal transition, inflammatory cytokines and cancer immunoediting

Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness. In this review we will outline how the dysregulation of microenvironmental signaling is crucial in determining tumor plasticity and EMT, arguing how therapy resistance hinges on these dynamics

Chitosan and its char as fillers in cement-base composites: A case study

Abstract The continuous research of new functional materials combining both advanced properties and increased sustainability has dramatically risen up in the last decades. Instead of searching for new solutions, composites (formed by a combination of already present materials) are subject of different studies due to their capability of merging the advantages of components. Hence, chitosan, a biowaste-derived biopolymer, has been thermally-converted into chars by pyrolysis treatment. Subsequently, both chitosan and its char are introduced into cementitious matrix forming cement-based composites. The analysis of the mechanical properties of these materials evidenced that char-containing composites show an incipient fracture toughness capability, very appealing for possible structural applications

Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer

Polyphenolic compounds, widely present in fruits, vegetables, and cereals, have potential benefits for human health and are protective agents against the development of chronic/degenerative diseases including cancer. More recently these bioactive molecules have been gaining great interest as anti-inflammatory and immunomodulatory agents, mainly in neoplasia where the pro-inflammatory context might promote carcinogenesis. Colorectal cancer (CRC) is considered a major public healthy issue, a leading cause of cancer mortality and morbidity worldwide. Epidemiological, pre-clinical and clinical investigations have consistently highlighted important relationships between large bowel inflammation, gut microbiota (GM), and colon carcinogenesis. Many experimental studies and clinical evidence suggest that polyphenols have a relevant role in CRC chemoprevention, exhibit cytotoxic capability vs. CRC cells and induce increased sensitization to chemo/radiotherapies. These effects are most likely related to the immunomodulatory properties of polyphenols able to modulate cytokine and chemokine production and activation of immune cells. In this review we summarize recent advancements on immunomodulatory activities of polyphenols and their ability to counteract the inflammatory tumor microenvironment. We focus on potential role of natural polyphenols in increasing the cell sensitivity to colon cancer therapies, highlighting the polyphenol-based combined treatments as innovative immunomodulatory strategies to inhibit the growth of CRC

Identification of a public CDR3 motif and a biased utilization of T-cell receptor V beta and J beta chains in HLA-A2/Melan-A-specific T-cell clonotypes of melanoma patients

<p>Abstract</p> <p>Background</p> <p>Assessment of T-cell diversity, besides giving insights about the molecular basis of tumor antigen recognition, has clinical implications since it provides criteria for evaluating antigen-specific T cells clinically relevant for spontaneous and vaccine-induced anti-tumor activity. Melan-A is one of the melanoma antigens most frequently recognized by peripheral and tumor-infiltrating lymphocytes in HLA-A2+ melanoma patients. Many clinical trials involving anti-tumor vaccination have been conducted using modified versions of this peptide.</p> <p>Methods</p> <p>We conducted an in-depth characterization of 210 T-cell receptor beta chain (TRB) clonotypes derived from T cells of HLA-A2+ melanoma patients displaying cytotoxic activity against natural and A27L-modified Melan-A peptides. One hundred and thirteen Melan-A-specific clonotypes from melanoma-free subjects, 199 clonotypes from T-cell clones from melanoma patients specific for melanoma antigens other than Melan-A, and 305 clonotypes derived from T cells of HLA-A2+ individuals showing unrelated specificities, were used as control. After sequence analysis, performed according to the IMGT definitions, TRBV and TRBJ usage, CDR3 length and amino acid composition were compared in the four groups of clonotypes.</p> <p>Results</p> <p>TRB sequences of Melan-A-specific clonotypes obtained from melanoma patients were highly heterogeneous, but displayed a preferential usage of few TRBV and TRBJ segments. Furthermore, they included a recurrent "public" amino acid motif (Glycine-Leucine-Glycine at positions 110-112-113 of the CDR3) rearranged with dominant TRBV and TRBJ segments and, in one case, associated with a full conservation of the entire TRB sequence.</p> <p>Conclusion</p> <p>Contrary to what observed for public anti-Melan-A T-cell receptor alpha motifs, which had been identified in several clonotypes of both melanoma patients and healthy controls, the unexpectedly high contribution of a public TRB motif in the recognition of a dominant melanoma epitope in melanoma patients may provide important information about the biology of anti-tumor T-cell responses and improve monitoring strategies of anti-tumor vaccines.</p

Magnitude of risks and benefits of the addition of bevacizumab to chemotherapy for advanced breast cancer patients: Meta-regression analysis of randomized trials

<p>Abstract</p> <p>Background</p> <p>Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile.</p> <p>Methods</p> <p>A literature-based meta-analysis to quantify the magnitude of benefit and safety of adding bevacizumab to chemotherapy for advanced breast cancer patients was conducted. Meta-regression and sensitivity analyses were also performed to identify additional predictors of outcome and to assess the influence of trial design.</p> <p>Results</p> <p>Five trials (3,841 patients) were gathered. A significant interaction according to treatment line was found for progression-free survival (PFS, p = 0.027); PFS was significantly improved for 1^stline (Hazard Ratio, HR 0.68, p < 0.0001), with a 1-yr absolute difference (AD) of 8.4% (number needed to treat, NNT 12). A non-significant trend was found in overall survival (OS), and in PFS for 2^ndline. Responses were improved with the addition of bevacizumab, without interaction between 1^stline (Relative Risk, RR 1.46, p < 0.0001) and 2^ndline (RR 1.58, p = 0.05). The most important toxicity was hypertension, accounting for a significant AD of 4.5% against bevacizumab (number needed to harm, NNH 22). Other significant, although less clinically meaningful, adverse events were proteinuria, neurotoxicity, febrile neutropenia, and bleeding. At the meta-regression analysis for 1^st-line, more than 3 metastatic sites (p = 0.032), no adjuvant chemotherapy (p = 0.00013), negative hormonal receptor status (p = 0.009), and prior anthracyclines-exposure (p = 0.019), did significantly affect PFS.</p> <p>Conclusions</p> <p>Although with heterogeneity, the addition of bevacizumab to 1^st-line chemotherapy significantly improves PFS, and overall activity. Hypertension should be weighted with the overall benefit on the individual basis.</p

Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals

Obesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery

WHO standards-based tools to measure service providers' and service users' views on the quality of hospital child care: development and validation in Italy

Objectives Evidence showed that, even in high-income countries, children and adolescents may not receive high quality of care (QOC). We describe the development and initial validation, in Italy, of two WHO standards-based questionnaires to conduct an assessment of QOC for children and young adolescents at inpatient level, based on the provider and user perspectives. Design Multiphase, mixed-methods study. Setting, participants and methods The two questionnaires were developed in four phases equally conducted for each tool. Phase 1 which included the prioritisation of the WHO Quality Measures according to predefined criteria and the development of the draft questionnaires. In phase 2 content face validation of the draft questionnaires was assessed among both experts and end-users. In phase 3 the optimised questionnaires were field tested to assess acceptability, perceived utility and comprehensiveness (N=163 end-users). In phase 4 intrarater reliability and internal consistency were evaluated (N=170 and N=301 end-users, respectively). Results The final questionnaires included 150 WHO Quality Measures. Observed face validity was excellent (kappa value of 1). The field test resulted in response rates of 98% and 76% for service users and health providers, respectively. Among respondents, 96.9% service users and 90.4% providers rated the questionnaires as useful, and 86.9% and 93.9%, respectively rated them as comprehensive. Intrarater reliability was good, with Cohen's kappa values exceeding 0.70. Cronbach alpha values ranged from 0.83 to 0.95, indicating excellent internal consistency. Conclusions Study findings suggest these tools developed have good content and face validity, high acceptability and perceived utility, and good intrarater reliability and internal consistency, and therefore could be used in health facilities in Italy and similar contexts. Priority areas for future research include how tools measuring paediatric QOC can be more effectively used to help health professionals provide the best possible care