Driving role of head and neck cancer cell secretome on the invasion of stromal fibroblasts: Mechanistic insights by phosphoproteomics.

Background: Cancer-associated fibroblasts (CAFs) are major players in tumor-stroma communication, and participate in several cancer hallmarks to drive tumor progression and metastatic dissemination. This study investigates the driving effects of tumor-secreted factors on CAF biology, with the ultimate goal of identifying effective therapeutic targets/strategies for head and neck squamous cell carcinomas (HNSCC).

Methods: Functionally, conditioned media (CM) from different HNSCC-derived cell lines and normal keratinocytes (Kc) were tested on the growth and invasion of populations of primary CAFs and normal fibroblasts (NFs) using 3D invasion assays in collagen matrices.

Clinical impact of rapid viral respiratory panel testing on pediatric critical care of patients with acute lower respiratory infection.

Background: We aimed to determine the impact of utilizing a rapid panel test of respiratory viral and atypical bacteria (FilmArray® Respiratory Panel, FA RP) on etiological diagnosis of acute lower respiratory infection (ALRI) and antimicrobial stewardship in critical care pediatric patients.

Methods: Prospective cohort study of patients aged<18 years with clinical diagnosis of ALRI that were admitted to the Pediatric Intensive Care Unit (PICU) of Hospital Sant Joan de Deu (Barcelona, Spain) during December 2015-February 2017. Patients were diagnosed by FA RP and by a bundle of routine microbiological assays.

Clinical impact of rapid viral respiratory panel testing on pediatric critical care of patients with acute lower respiratory infection.

Background: We aimed to determine the impact of utilizing a rapid panel test of respiratory viral and atypical bacteria (FilmArray® Respiratory Panel, FA RP) on etiological diagnosis of acute lower respiratory infection (ALRI) and antimicrobial stewardship in critical care pediatric patients.

Methods: Prospective cohort study of patients aged<18 years with clinical diagnosis of ALRI that were admitted to the Pediatric Intensive Care Unit (PICU) of Hospital Sant Joan de Deu (Barcelona, Spain) during December 2015-February 2017. Patients were diagnosed by FA RP and by a bundle of routine microbiological assays.

Expression of E-cadherin and β-catenin in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas.

Introduction And Objectives: Dysfunction of the E-cadherin/catenin complex is directly related to carcinogenesis and metastases development. The aim of this paper is to investigate the prognostic significance of E-cadherin and β-catenin expression in surgically treated laryngeal and hypopharyngeal squamous cell carcinomas.

Material And Methods: Tumour tissue samples were obtained from 133 consecutive patients with squamous cell carcinomas of the head and neck: 68 of the larynx and 65 hypopharyngeal carcinomas, who underwent surgical treatment in our hospital between 2000 and 2005.

The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy.

The SRC Inhibitor Dasatinib Induces Stem Cell-Like Properties in Head and Neck Cancer Cells that are Effectively Counteracted by the Mithralog EC-8042.

The frequent dysregulation of SRC family kinases (SFK) in multiple cancers prompted various inhibitors to be actively tested in preclinical and clinical trials. Disappointingly, dasatinib and saracatinib failed to demonstrate monotherapeutic efficacy in patients with head and neck squamous cell carcinomas (HNSCC). Deeper functional and mechanistic knowledge of the actions of these drugs is therefore needed to improve clinical outcome and to develop more efficient combinational strategies.

"The big sleep: Elucidating the sequence of events in the first hours of death to determine the postmortem interval".

Recent developments on postmortem interval estimation (PMI) take an advantage of the autolysis process, pointing out to the analysis of the expression of apoptosis and autophagy genes towards this purpose. Oxidative stress plays a role in this signaling as a regulatory mechanism and/or as a consequence of cell death. Additionally, melatonin has been implicated on apoptosis and autophagy signaling, making melatonin a suitable target for PMI determination.

Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients.

Clear differences have been established between head and neck squamous cell carcinomas (HNSCC) depending on human papillomavirus (HPV) infection status. This study specifically investigated the status of the , and genes mapping at the 11q13 amplicon in relation to the HPV status in HNSCC patients. CTTN, CCND1 and ANO1 protein expression and gene amplification were respectively analyzed by immunohistochemistry and real-time PCR in a homogeneous cohort of 392 surgically treated HNSCC patients.

Factors Secreted by Cancer-Associated Fibroblasts that Sustain Cancer Stem Properties in Head and Neck Squamous Carcinoma Cells as Potential Therapeutic Targets.

This study investigates for the first time the crosstalk between stromal fibroblasts and cancer stem cell (CSC) biology in head and neck squamous cell carcinomas (HNSCC), with the ultimate goal of identifying effective therapeutic targets. The effects of conditioned media from cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) on the CSC phenotype were assessed by combining functional and expression analyses in HNSCC-derived cell lines. Further characterization of CAFs and NFs secretomes by mass spectrometry was followed by pharmacologic target inhibition.

Physicochemical and microbiological stability of two news oral liquid formulations of clonidine hydrochloride for pediatric patients.

Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients.

Immunohistochemical Expression of Cortactin and Focal Adhesion Kinase Predicts Recurrence Risk and Laryngeal Cancer Risk Beyond Histologic Grading.

Cortactin () and the focal adhesion kinase () are two major candidate genes to, respectively, drive 11q13- and 8q24-associated aggressive behavior in various cancers. Recent evidence uncovered their clinical relevance in early stages of tumorigenesis as promising biomarkers for cancer risk assessment. Using a multicenter validation study, CTTN and FAK expression was evaluated by immunohistochemistry (IHC) in a cohort of 109 patients with laryngeal precancerous lesions, and correlated with clinicopathologic parameters and laryngeal cancer risk.

Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system.

Background: The SLC39A14, SLC30A10 and SLC39A8 are considered to be key genes involved in manganese (Mn) homeostasis in humans. Mn levels in plasma and urine are useful tools for early recognition of these disorders. We aimed to explore further biomarkers of Mn deposition in the central nervous system in two siblings presenting with acute dystonia and hypermanganesemia due to mutations in SLC39A14.

Analysis of Invasive Activity of CAF Spheroids into Three Dimensional (3D) Collagen Matrices.

Tumor growth and progression is the result of a complex process controlled not only by malignant cancer cells but also by the surrounding tumor microenvironment (TME). Cancer associated fibroblasts (CAFs), the most abundant cellular component of TME, play an active role in tumor invasion and metastasis by promoting cancer cell invasion through cell-cell interactions and secretion of pro-invasive factors such as extracellular matrix (ECM)-degrading proteases. Due to their tumor-promoting activities, there is an emerging interest in investigating CAFs biology and its potential as drug targets for cancer therapies.

Dysregulation of Mir-196b in Head and Neck Cancers Leads to Pleiotropic Effects in the Tumor Cells and Surrounding Stromal Fibroblasts.

The miR-196 family members have been found dysregulated in different cancers. Therefore, they have been proposed as promising biomarkers and therapeutic targets. This study is the first to investigate the role of miR-196b in the development and progression of head and neck squamous cell carcinomas (HNSCC), and also the impact on the surrounding tumor microenvironment.

A Novel Role For Nanog As An Early Cancer Risk Marker In Patients With Laryngeal Precancerous Lesions.

NANOG is a master regulator of embryonic stem cell pluripotency, found to be frequently aberrantly expressed in a variety of cancers, including laryngeal carcinomas. This study investigates for the first time the role of NANOG expression in early stages of laryngeal tumourigenesis and its potential utility as cancer risk marker. NANOG protein expression was evaluated by immunohistochemistry using two large independent cohorts of patients with laryngeal precancerous lesions, and correlated with clinicopathological parameters and laryngeal cancer risk.

Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b.

Annexin A1 (ANXA1) down-regulation is an early and frequent event in the development of head and neck squamous cell carcinomas (HNSCC). In an attempt to identify the underlying mechanisms of reduced ANXA1 protein expression, this study investigated ANXA1 mRNA expression in HNSCC specimens by both in situ hybridization and RT-qPCR. Results showed a perfect concordance between the pattern of ANXA1 mRNA and protein detected by immunofluorescence in tumors, precancerous lesions and normal epithelia, reflecting that ANXA1 down-regulation occurs at transcriptional level.

Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells.

Fibulin-2 participates in the assembly of extracellular matrix components through interactions with multiple ligands and promotes contacts between cells and their surrounding environment. Consequently, identification of processes that could lead to an altered Fibulin-2 could have a major impact not only in the maintenance of tissue architecture and morphogenesis but also in pathological situations including cancer. Herein, we have investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2.

HERG1 potassium channel expression in potentially malignant disorders of the oral mucosa and prognostic relevance in oral squamous cell carcinoma.

Background: HERG1 potassium channel plays a critical role in the cell proliferation.

Methods: HERG1 protein expression was analyzed by immunohistochemistry (IHC) in 62 patients with oral leukoplakias and 100 patients with oral squamous cell carcinomas (OSCC). HERG1 mRNA levels were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 patients with primary head and neck squamous cell carcinoma (HNSCC).

Impact of PI3K/AKT/mTOR pathway activation on the prognosis of patients with head and neck squamous cell carcinomas.

The PI3K/AKT/mTOR signaling pathway has emerged as one of the most frequently deregulated in head and neck squamous cell carcinomas (HNSCC). Numerous alterations of various upstream and downstream components have been described; however, their prognostic significance and impact on HNSCC patient survival remains to be established. This was addressed using an unbiased cohort of 93 consecutive and homogeneous surgically treated HNSCC patients and results confirmed in 432 HNSCC patients.

HERG1A potassium channel is the predominant isoform in head and neck squamous cell carcinomas: evidence for regulation by epigenetic mechanisms.

Evidences indicate that HERG1 voltage-gated potassium channel is frequently aberrantly expressed in various cancers including head and neck squamous cell carcinomas (HNSCC), representing a clinically and biologically relevant feature during disease progression and a potential therapeutic target. The present study further and significantly extends these data investigating for the first time the expression and individual contribution of HERG1 isoforms, their clinical significance during disease progression and also the underlying regulatory mechanisms. Analysis of HERG1A and HERG1B expression using real-time RT-PCR consistently showed that HERG1A is the predominant isoform in ten HNSCC-derived cell lines tested.

Clinical significance of Anoctamin-1 gene at 11q13 in the development and progression of head and neck squamous cell carcinomas.

This study investigates the clinical significance of Anoctamin-1 gene mapping at 11q13 amplicon in both the development and progression of head and neck squamous cell carcinomas (HNSCC). ANO1 protein expression was evaluated by immunohistochemistry in a cohort of 372 surgically treated HNSCC patients and also in 35 laryngeal precancerous lesions. ANO1 gene amplification was determined by real-time PCR in all the laryngeal premalignancies and 60 of the HNSCCs, and molecular data correlated with clinical outcome.

Glutamine effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children.

Background & Aims: To determine whether glutamine (Gln) supplementation would have a role modifying both the oxidative stress and the inflammatory response of critically ill children.

Methods: Prospective, randomized, double-blind, interventional clinical trial. Selection criteria were children requiring parenteral nutrition for at least 5 days diagnosed with severe sepsis or post major surgery.

eIF2 kinases mediate β-lapachone toxicity in yeast and human cancer cells.

β-Lapachone (β-lap) is a novel anticancer agent that selectively induces cell death in human cancer cells, by activation of the NQO1 NAD(P)H dehydrogenase and radical oxygen species (ROS) generation. We characterized the gene expression profile of budding yeast cells treated with β-lap using cDNA microarrays. Genes involved in tolerance to oxidative stress were differentially expressed in β-lap treated cells.

Profile of prescribing errors detected by clinical pharmacists in paediatric hospitals in Spain.

Background: Pharmaceutical care involves three essential functions: identifying potential and real medication-related problems, solving real medication-related problems and preventing potential medication related problems.

Objective: To describe the profile of prescribing errors detected and prevented by paediatric clinical pharmacists in medical orders for inpatients in Spain.

Settings And Methods: A prospective, descriptive, multicentre epidemiological study on medical orders for inpatients aged 1 day to 18 years, conducted between July and October 2011 at eight hospitals treating paediatric patients.