Triple positive breast cancer. A distinct subtype?

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets

Panel on “Past and future of computer science theory”

The twenty-ninth edition of the SEBD (Italian Symposium on Advanced Database Systems), held on 5-9 September 2021 in Pizzo (Calabria Region, Italy), included a joint seminar on “Reminiscence of TIDB 1981” with invited talks given by some of the participants to the Advanced Seminar on Theoretical Issues in Databases (TIDB), which took place in the same region exactly forty years earlier. The joint seminar was concluded by a Panel on “The Past and the Future of Computer Science Theory” with the participation of four distinguished computer science theorists (Ronald Fagin, Georg Gottlob, Christos Papadimitriou and Moshe Vardi), who were interviewed by Giorgio Ausiello, Maurizio Lenzerini, Luigi Palopoli, Domenico Saccà and Francesco Scarcello. This paper reports the summaries of the four interviews

Subarachnoid versus General Anesthesia in Penile Prosthetic Implantation: Outcomes Analyses

The leading patient complaint during the perioperative period for penile prosthesis implantation is postoperative pain, while emesis and urticaria also affect the procedure’s perceived success. In analyzing surgical outcomes, assessment of the anesthetic for postoperative pain and side effects should be included. This paper retrospectively reviews 90 consecutive, primary inflatable penile prosthetic operations performed by a single surgeon at one private medical center. Fifty-seven patients were included in final analysis. Patients who had more than one procedure that day or who used chronic pain medication were excluded. The type and amount of each drug used for each respective side effect (within the first 24 hours after procedure) were compared to determine relative benefit. Twenty patients received general anesthesia (denoted herein as “GA”) and 37 received spinal (or also known as subarachnoid) anesthesia (denoted herein as “SA”). Patients receiving GA had significantly greater (P<0.0001) occurrence and amount of intravenous pain treatment than those receiving SA. Patients with SA required less intravenous pain medication and less treatment for nausea/emesis

Efgartigimod improved health-related quality of life in generalized myasthenia gravis: results from a randomized, double-blind, placebo-controlled, phase 3 study (ADAPT)

There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG.Neurological Motor Disorder

Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo

Trabecular Meshwork Gene Expression after Selective Laser Trabeculoplasty

BACKGROUND: Trabecular meshwork and Schlemm's canal are the tissues appointed to modulate the aqueous humour outflow from the anterior chamber. The impairment of their functions drives to an intraocular pressure increase. The selective laser trabeculoplasty is a laser therapy of the trabecular meshwork able to decrease intraocular pressure. The exact response mechanism to this treatment has not been clearly delineated yet. The herein presented study is aimed at studying the gene expression changes induced in trabecular meshwork cells by selective laser trabeculoplasty (SLT) in order to better understand the mechanisms subtending its efficacy. METHODOLOGY/PRINCIPAL FINDINGS: Primary human trabecular meshwork cells cultured in fibroblast medium underwent selective laser trabeculoplasty treatment. RNA was extracted from a pool of cells 30 minutes after treatment while the remaining cells were further cultured and RNA was extracted respectively 2 and 6 hours after treatment. Control cells stored in incubator in absence of SLT treatment were used as reference samples. Gene expression was evaluated by hybridization on miRNA-microarray and laser scanner analysis. Scanning electron microscopic examination was performed on 2 Trabecular meshwork samples after SLT at 4(th) and 6(th) hour from treatment. On the whole, selective laser trabeculoplasty modulates in trabecular meshwork the expression of genes involved in cell motility, intercellular connections, extracellular matrix production, protein repair, DNA repair, membrane repair, reactive oxygen species production, glutamate toxicity, antioxidant activities, and inflammation. CONCLUSIONS/SIGNIFICANCE: SLT did not induce any phenotypic alteration in TM samples. TM is a complex tissue possessing a great variety of function pivotal for the active regulation of aqueous humour outflow from the anterior chamber. SLT is able to modulate these functions at the postgenomic molecular level without inducing damage either at molecular or phenotypic levels

Androgen receptor and antiandrogen therapy in male breast cancer

Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative ther- apeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an over- view of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients

Test of GET Electronics for the CHIMERA and FARCOS multi-detectors

open30openDe Luca, S.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D'Andrea, M.; De Filippo, E.; Dell'Aquila, D.; Fichera, F.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; Lombardo, I.; Martorana, N. S.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Sacca', G.; Trifiro', A.; Trimarchi, M.; Verde, G.; Vigilante, M.De Luca, S.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, GIUSEPPE MICHELE OSVALDO; Castoldi, Andrea; D'Andrea, M.; De Filippo, E.; Dell'Aquila, D.; Fichera, F.; Gnoffo, B.; Guazzoni, Chiara; Lanzalone, G.; Lombardo, I.; Martorana, N. S.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Sacca', G.; Trifiro', A.; Trimarchi, M.; Verde, G.; Vigilante, M

The T.O.S.C.A. Project: Research, Education and Care

Despite recent and exponential improvements in diagnostic- therapeutic pathways, an existing “GAP” has been revealed between the “real world care” and the “optimal care” of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF “metabolic pathophysiological model” and to improve the quality of care of HF patients through research and continuing medical education