Search results for "Genes"

2019

Sinus node dysfunction (SND) and atrial fibrillation (AF) often coexist; however, the molecular mechanisms linking both conditions remain elusive. Mutations in the homeobox-containing SHOX2 gene have been recently associated with early-onset and familial AF. Shox2 is a key regulator of sinus node development, and its deficiency leads to bradycardia, as demonstrated in animal models. To provide an extended SHOX2 gene analysis in patients with distinct arrhythmias, we investigated SHOX2 as a susceptibility gene for SND and AF by screening 98 SND patients and 450 individuals with AF. The functional relevance of the novel mutations was investigated in vivo and in vitro, together with the previo…

The Effects of Early Life Stress on the Brain and Behaviour: Insights From Zebrafish Models

2021

The early life period represents a window of increased vulnerability to stress, during which exposure can lead to long-lasting effects on brain structure and function. This stress-induced developmental programming may contribute to the behavioural changes observed in mental illness. In recent decades, rodent studies have significantly advanced our understanding of how early life stress (ELS) affects brain development and behaviour. These studies reveal that ELS has long-term consequences on the brain such as impairment of adult hippocampal neurogenesis, altering learning and memory. Despite such advances, several key questions remain inadequately answered, including a comprehensive overview…

The potential of cystatin C as a predictive biomarker in breast cancer

2020

Breast cancer (BCa) is the leading cause of cancer-related deaths among women. Numerous efforts are being directed toward identifying novel tissue and/or circulating molecular markers that may help clinicians in detecting early-stage BCa patients and in providing an accurate estimation of the prognosis and prediction of response to clinical treatments. In this setting, emerging evidence has indicated Cystatin C (Cyst C), as the most potent endogenous inhibitor of cysteine cathepsins, as a possible useful marker in the clinical management of BCa patients.This review analyzes the results of emerging studies underpinning a potential clinical role of Cyst C, as additional marker in BCa.Cyst C e…

2018

A headlight on liquid biopsies: a challenging tool for breast cancer management

2016

Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g., PI3K/Akt/mTOR, PTEN, TP53). To date, diagnosis and metastasis monitoring is mainly carried out through tissue biopsy and/or re-biopsy, a very invasive procedure limited only to certain locations and not always feasible in clinical practice. In order to improve disease monitoring over time and to avoid painful procedure such as tissue biopsy, liquid biopsy may represent a new precious tool. Indeed, it represents a bas…

Critical Roles of EGFR family members in breast cancer and breast cancer stem cells: Targets for therapy

2016

The roles of the epidermal growth factor receptor (EGFR) signaling pathway in various cancers including breast, bladder, brain, colorectal, esophageal, gastric, head and neck, hepatocellular, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and other cancers have been keenly investigated since the 1980's. While the receptors and many downstream signaling molecules have been identified and characterized, there is still much to learn about this pathway and how its deregulation can lead to cancer and how it may be differentially regulated in various cell types. Multiple inhibitors to EGFR family members have been developed and many are in clinical use. Current research often focuses o…

The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target.

2020

Gastric cancer (GC) represents the fifth cause of cancer-related death worldwide. Molecular biology has become a central area of research in GC and there are currently at least three major classifications available to elucidate the mechanisms that drive GC oncogenesis. Further, tumor microenvironment seems to play a crucial role, and tumor-associated macrophages (TAMs) are emerging as key players in GC development. TAMs are cells derived from circulating chemokine- receptor-type 2 (CCR2) inflammatory monocytes in blood and can be divided into two main types, M1 and M2 TAMs. M2 TAMs play an important role in tumor progression, promoting a pro-angiogenic and immunosuppressive signal in the tu…

Intervention of Inflammatory Monocyte Activity Limits Dermal Fibrosis

2019

Monocytes and monocyte-derived cells are important players in the initiation, progression, and resolution of inflammatory skin reactions. As inflammation is a prerequisite for fibrosis development, we focused on the role of monocytes in cutaneous fibrosis, the clinical hallmark of patients suffering from systemic sclerosis. Investigating the function of monocytes in reactive oxygen species–induced dermal fibrosis, we observed that early monocyte depletion partially reduced disease severity. Low numbers of inflammatory Ly6Chigh monocytes, as well as inhibition of CCR2 and CCL2 in wild type animals by a specific L-RNA aptamer, mitigated disease parameters, indicating a pivotal role for CCR2+ …

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell …

2021

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus’ complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA– memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA– memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vita…

The embryo-placental CD15-positive "vasculogenic zones" as a source of propranolol-sensitive pediatric vascular tumors.

2015

Abstract Objective Propranolol-induced involution is a unique biological feature of some pediatric vascular tumors, for instance infantile hemangioma (IH), cerebral cavernoma or chorioangioma. Currently, the cellular origin of these distinct tumors is unclear. In this study, we tested the hypothesis that propranolol-responsive vascular tumors are derived from common vessel-forming CD15 + progenitor cells which occur in early gestation. The aim of this study was to identify the tumor-relevant CD15 + progenitors at the early stages of embryo-placental development. Materials and methods Human embryo-placental units of 4–8 weeks gestation and pediatric vascular tumors were tested for expression…