Ricerc@Sapienza

PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules that trigger the poly-ubiquitination of the protein of interest (POI) inducing its degradation via the recruitment of the ubiquitin-proteasome system, thus suppressing the POI's intracellular levels and indirectly all its functions. Recently, one of the fields where the protein knockdown induced by PROTACs has demonstrated to serve as a promising biochemical tool and to provide new opportunities for drug discovery is the epigenetics (epi-PROTACs).

Introduction: Diet may influence various aspects of human health. In fact, it is well known that diet can favour or not the development of various human pathologies, like diabetes, hypertension, and hypercholesterolaemia. Interestingly, diet has an influence in cancer development too (e.g., this relation has been studied for pancreatic, colonic, gastric, and breast cancers). Between the mechanisms that could explain this relation, there is epigenetic.

Cardiovascular diseases, chronic obstructive pulmonary diseases, diabetes, rheumatoid arthritis, and cancer are the most common noncommunicable diseases (NCDs). These NCDs share risk factors with periodontal disease (PD), a preventable risk factor linked to lifestyle. The discussion regarding the association between these chronic diseases is more complex. There is still a significant knowledge gap particularly of the causal relationship between PD and NCDs.

Aim: To realize and characterize a new generation of keratin-coated gold nanoparticles (Ker-AuNPs) as highly efficient photosensitive nanosized therapeutics for plasmonic photothermal (PPT) therapy. Materials & methods: The chemical, physical, morphological and photothermal properties of Ker-AuNPs are investigated using dynamic light scattering, ζ-potential, UV–Visible, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, transmission electron microscopy and high-resolution thermography.

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile.

Introduction: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. Area covered: This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review.

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy.

Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radio- and chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time.

Objective: Stressful life events (SLEs) impact the quality of life (QOL) of cancer patients. This study investigated the mediation of the relationship between SLEs and QOL (Model 1: Emotional-EQOL and Model 2: Physical/Functional-PFQOL by three types of coping: Action/Planning, Support/Advise-Seeking, and Disengagement/Denial). Design and Main Measures: 662 persons with cancer completed a Stressful Life Events Checklist, the Brief COPE scale, the FACT Emotional, Physical, and Functional Scales, and the Physical Impact Scale of the Sickness Impact Profile.

We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4).