Corrigendum: Estrogens modulate somatostatin receptors expression and synergize with the somatostatin analog pasireotide in prostate cells.

[This corrects the article DOI: 10.3389/fphar.2019.

Combined Therapeutic Strategies Based on the Inhibition of Non-Oncogene Addiction to Improve Tumor Response in EGFR- and KRAS-Mutant Non-Small-Cell Lung Cancer.

Background: Oncogene-driven NSCLC is usually treated with targeted therapies using tyrosine kinase inhibitors (TKIs) to inhibit oncogene downstream signaling pathways, affecting tumor survival and proliferation. EGFR- and KRAS-mutant NSCLCs are the most represented subtypes, and they are treated in clinical practice with oncogene-targeting drugs in the first and second line, respectively. Unfortunately, the development of oncogene-independent resistant clones limits TKI efficacy.

Discovery of -substituted-2-oxoindolin benzoylhydrazines as c-MET/SMO modulators in EGFRi-resistant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), the leading cause of cancer-related mortality worldwide, poses a formidable challenge due to its heterogeneity and the emergence of resistance to targeted therapies. While initially effective, first- and third-generation EGFR-tyrosine kinase inhibitors (TKIs) often fail to control disease progression, leaving patients with limited treatment options. To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC.

ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors.

Background: ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which provides metabolic intermediates to sustain cell proliferation. The aim of our study is to elucidate the role of ATM in the regulation of glucose metabolism in oncogene-driven cancer cells and to test whether ATM may be a suitable target for anticancer therapy.

Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation.

Background: T cell activation and programming from their naïve/resting state, characterized by widespread modifications in chromatin accessibility triggering extensive changes in transcriptional programs, is orchestrated by several cytokines and transcription regulators. PRDM1 and PRDM2 encode for proteins with PR/SET and zinc finger domains that control several biological processes, including cell differentiation, through epigenetic regulation of gene expression. Different transcripts leading to main protein isoforms with (PR +) or without (PR-) the PR/SET domain have been described.

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models.

Positive Regulatory Domain (PRDM) gene family members commonly express two main molecular variants, the PR- isoform usually acting as tumor suppressor and the PR- one functioning as oncogene. Accordingly, PRDM2/RIZ encodes for RIZ1 (PR-) and RIZ2 (PR-). In human cancers, genetic or epigenetic modifications induce RIZ1 silencing with an expression level imbalance in favor of RIZ2 that could be relevant for tumorigenesis.

Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life.

Background: The use of dasatinib and nilotinib in the treatment of patients with chronic myeloid leukemia represents a valid therapeutic option for patients resistant or intolerant to imatinib. In this multicentre study, adherence, persistence and efficacy in real life over two years of treatment were evaluated.

Materials And Methods: Adherence to treatment was calculated as the ratio between the dose received and the prescribed dose.

Estrogens Modulate Somatostatin Receptors Expression and Synergize With the Somatostatin Analog Pasireotide in Prostate Cells.

Prostate cancer (PC) is one of the most frequently diagnosed cancers and a leading cause of cancer-related deaths in Western society. Current PC therapies prevalently target the functions of androgen receptor (AR) and may only be effective within short time periods, beyond which the majority of PC patients progress to castration-resistant PC (CRPC) and metastatic disease. The role of estradiol/estradiol receptor (ER) axis in prostate transformation and PC progression is well established.

Dysfunctional personality traits in adolescence: effects on alerting, orienting and executive control of attention.

The present study examined attentional networks performance in 39 adolescents with dysfunctional personality traits, split into two group, Group < 10 and Group ≥ 10, according to the number of criteria they met at the Structured Clinical Interview for DSM-IV Axis II Personality Disorders. The attentional performance has been tested by means of a modified version of the Attentional Network Test (ANTI-V) which allows testing both phasic and tonic components of the alerting system, the exogenous aspect of the orienting system, the executive network and their interactions. Results showed that the orienting costs of having an invalid spatial cue were reduced in the Group ≥ 10 criteria compared to the Group < 10.

Mouse monoclonal antibodies against estrogen receptor.

The production of monoclonal antibodies, by cloning hybridoma derived from the fusion of myeloma cells and spleen lymphocytes, has allowed to obtain great advances in many fields of biological knowledge. The use of specific antibodies to the estrogen receptor, in fact, has been an invaluable method to bring out its mechanisms of action and its effects, both genomic and extra-genomic. Here we describe, step by step, the production of monoclonal antibodies, starting from protocol for antigen preparation to the selection of antibody-secreting hybridoma.

Visual search and emotion: how children with autism spectrum disorders scan emotional scenes.

This study assessed visual search abilities, tested through the flicker task, in children diagnosed with autism spectrum disorders (ASDs). Twenty-two children diagnosed with ASD and 22 matched typically developing (TD) children were told to detect changes in objects of central interest or objects of marginal interest (MI) embedded in either emotion-laden (positive or negative) or neutral real-world pictures. The results showed that emotion-laden pictures equally interfered with performance of both ASD and TD children, slowing down reaction times compared with neutral pictures.

[Executive function deficits in ADHD and Asperger syndrome].

Background: The aim of this study is to evaluate the executive functioning of children with attention deficit hyperactivity disorder combined subtype (ADHD-C) and Asperger syndrome (AS) compared to a control group.

Methods: A sample of 79 children (28 ADHD-C; 24 AS; 27 subjects with typical development) was tested on a wide range of tasks related to major domains of executive functioning: inhibition response (prepotent and interference), visual working memory, planning and cognitive flexibility.

Results: Patients with AS showed deficits on visual working memory and cognitive flexibility.

Impaired reflexive orienting to social cues in attention deficit hyperactivity disorder.

The present study investigated whether another person's social attention, specifically the direction of their eye gaze, and non-social directional cues triggered reflexive orienting in individuals with Attention Deficit Hyperactivity Disorder (ADHD) and age-matched controls. A choice reaction time and a detection tasks were used in which eye gaze, arrow and peripheral cues correctly (congruent) or incorrectly (incongruent) signalled target location. Independently of the type of the task, differences between groups were specific to the cue condition.

Human endogenous retroviruses and ADHD.

Objectives: Several lines of evidences suggest that human endogenous retroviruses (HERVs) are implicated in the development of many complex diseases with a multifactorial aetiology and a strong heritability, such as neurological and psychiatric diseases. Attention deficit hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that results from a complex interaction of environmental, biological and genetic factors. Our aim was to analyse the expression levels of three HERV families (HERV-H, K and W) in patients with ADHD.

PRDM Proteins: Molecular Mechanisms in Signal Transduction and Transcriptional Regulation.

PRDM (PRDI-BF1 and RIZ homology domain containing) protein family members are characterized by the presence of a PR domain and a variable number of Zn-finger repeats. Experimental evidence has shown that the PRDM proteins play an important role in gene expression regulation, modifying the chromatin structure either directly, through the intrinsic methyltransferase activity, or indirectly through the recruitment of chromatin remodeling complexes. PRDM proteins have a dual action: they mediate the effect induced by different cell signals like steroid hormones and control the expression of growth factors.

Inhibition of return in response to eye gaze and peripheral cues in young people with Asperger's syndrome.

Inhibition of return (IOR) reflects slower reaction times to stimuli presented in previously attended locations. In this study, we examined this inhibitory after-effect using two different cue types, eye-gaze and standard peripheral cues, in individuals with Asperger's syndrome and typically developing individuals. Typically developing participants showed evidence of IOR for both eye-gaze and peripheral cues.

Detecting anxiety symptoms in children and youths with neurofibromatosis type I.

Children with Neurofibromatosis type 1 (NF1) are known to have cognitive, social, and behavioral deficits. Fifteen NF1-subjects (5 boys, 10 girls, mean age = 13.4), and 15 healthy controls matched for age and sex were assessed on the presence of anxiety symptoms, using the Multidimensional Anxiety Scale for Children (MASC), self-report questionnaire.

Change blindness in children with ADHD: a selective impairment in visual search?

Objective: This study evaluated change blindness and visual search efficiency in children with ADHD in searching for central and marginal changes.

Method: A total of 36 drug-naïve children (18 ADHD/18 controls) performed a flicker task that included changes in objects of central or marginal interest. The task required observers to search for a change until they detected it.

Assessing attentional systems in children with Attention Deficit Hyperactivity Disorder.

The aim of this study was to evaluate the efficiency and interactions of attentional systems in children with Attention Deficit Hyperactivity Disorder (ADHD) by considering the effects of reinforcement and auditory warning on each component of attention. Thirty-six drug-naïve children (18 children with ADHD/18 typically developing children) performed two revised versions of the Attentional Network Test, which assess the efficiency of alerting, orienting, and executive systems. In feedback trials, children received feedback about their accuracy, whereas in the no-feedback trials, feedback was not given.

Highlighting chromosome loops in DNA-picked chromatin (DPC).

Growing evidence supports the concept that dynamic intra- and inter-chromosomal links between specific loci contribute to the creation of cell-type specific gene expression profiles. Therefore, analysis of the establishment of peculiar functional correlations between sites, also distant on linear DNA, that govern the transcriptional process appears to be of fundamental relevance. We propose here an experimental approach showing that 17β-estradiol-induced transcription associates to formation of loops between the promoter and termination regions of hormone-responsive genes.

Identification of a functional estrogen-responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines.

The retinoblastoma protein-interacting zinc-finger (RIZ) gene, also known as PRDM2, encodes two protein products, RIZ1 and RIZ2, differing for the presence of a 202 aa domain, called PR domain, at the N-terminus of the RIZ1 molecule. While the histone H3 K9 methyltransferase activity of RIZ1 is associated with the negative control of cell proliferation, no information is currently available on either expression regulation of the RIZ2 form or on its biological activity. RIZ proteins act as ER co-activators and promote optimal estrogen response in female reproductive tissues.

Differential expression of cyclooxygenases in hypertrophic scar and keloid tissues.

Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-beta, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2).