Transcriptomic and epigenetic landscape of nimorazole-enhanced radiochemotherapy in head and neck cancer.

Background: Hypoxia remains a challenge for the therapeutic management of head and neck squamous cell carcinoma (HNSCC). The combination of radiotherapy with nimorazole has shown treatment benefit in HNSCC, but the precise underlying molecular mechanisms remain unclear.

Purpose: To assess and to characterize the transcriptomic/epigenetic landscape of HNSCC tumor models showing differential therapeutic response to fractionated radiochemotherapy (RCTx) combined with nimorazole.

Enhancing mass spectrometry imaging accessibility using convolutional autoencoders for deriving hypoxia-associated peptides from tumors.

Mass spectrometry imaging (MSI) allows to study cancer's intratumoral heterogeneity through spatially-resolved peptides, metabolites and lipids. Yet, in biomedical research MSI is rarely used for biomarker discovery. Besides its high dimensionality and multicollinearity, mass spectrometry (MS) technologies typically output mass-to-charge ratio values but not the biochemical compounds of interest.

Epigenetic Targeting to Overcome Radioresistance in Head and Neck Cancer.

(1) Background: The sensitivity of head and neck squamous cell carcinoma (HNSCC) to ionizing radiation, among others, is determined by the number of cells with high clonogenic potential and stem-like features. These cellular characteristics are dynamically regulated in response to treatment and may lead to an enrichment of radioresistant cells with a cancer stem cell (CSC) phenotype. Epigenetic mechanisms, particularly DNA and histone methylation, are key regulators of gene-specific transcription and cellular plasticity.

Corrigendum: FXYD5/Dysadherin, a biomarker of endometrial cancer myometrial invasion and aggressiveness: its relationship with TGF-β1 and NF-κB pathways.

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

Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts.

Background: Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use.

Plasticity within Aldehyde Dehydrogenase-Positive Cells Determines Prostate Cancer Radiosensitivity.

Unlabelled: Tumor heterogeneity and cellular plasticity are key determinants of tumor progression, metastatic spread, and therapy response driven by the cancer stem cell (CSC) population. Within the current study, we analyzed irradiation-induced plasticity within the aldehyde dehydrogenase (ALDH)-positive (ALDH+) population in prostate cancer. The radiosensitivity of xenograft tumors derived from ALDH+ and ALDH-negative (ALDH-) cells was determined with local tumor control analyses and demonstrated different dose-response profiles, time to relapse, and focal adhesion signaling.

Tyrosine Kinase c-MET as Therapeutic Target for Radiosensitization of Head and Neck Squamous Cell Carcinomas.

The receptor tyrosine kinase c-MET activates intracellular signaling and induces cell proliferation, epithelial-to-mesenchymal-transition and migration. Within the present study, we validated the prognostic value of c-MET in patients with head and neck squamous cell carcinoma (HNSCC) treated with radio(chemo)therapy using the Cancer Genome Atlas database and found an association of increased gene expression and protein phosphorylation with reduced disease-specific and progression-free survival. To investigate the role of c-MET-dependent radioresistance, c-MET-positive cells were purified from established HNSCC cell lines and a reduced radiosensitivity and enhanced sphere-forming potential, compared to the c-MET-depleted cell population, was found in two out of four analyzed cell lines pointing to regulatory heterogeneity.

Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools.

Endometrial cancer (EC) is the sixth most common cancer in women worldwide. Early diagnosis is critical in recurrent EC management. The present study aimed to identify biomarkers of EC early recurrence using a workflow that combined text and data mining databases (DisGeNET, Gene Expression Omnibus), a prioritization algorithm to select a set of putative candidates (ToppGene), protein‑protein interaction network analyses (Search Tool for the Retrieval of Interacting Genes, cytoHubba), association analysis of selected genes with clinicopathological parameters, and survival analysis (Kaplan‑Meier and Cox proportional hazard ratio analyses) using a The Cancer Genome Atlas cohort.

Ephrin-B1 Is a Novel Biomarker of Bladder Cancer Aggressiveness. Studies in Murine Models and in Human Samples.

Bladder cancer (BC) is the ninth most common cancer worldwide, but molecular changes are still under study. During tumor progression, Epithelial cadherin (E-cadherin) expression is altered and β-catenin may be translocated to the nucleus, where it acts as co-transcription factor of tumor invasion associated genes. This investigation further characterizes E-cadherin and β-catenin associated changes in BC, by combining bioinformatics, an experimental murine cell model (MB49/MB49-I) and human BC samples.

FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness: Its Relationship With TGF-β1 and NF-κB Pathways.

Endometrial cancer (EC) is the second most common gynecological cancer worldwide. Myometrial invasion (MI) is a key event in EC dissemination. This study aimed to evaluate FXYD5/dysadherin (FXYD5/Dys) expression in EC tissue and uterine aspirate (UA) biopsies and to assess molecular/functional changes associated with its expression in cellular models.

Characterization of the molecular changes associated with the overexpression of a novel epithelial cadherin splice variant mRNA in a breast cancer model using proteomics and bioinformatics approaches: identification of changes in cell metabolism and an increased expression of lactate dehydrogenase B.

Background: Breast cancer (BC) is the most common female cancer and the leading cause of cancer death in women worldwide. Alterations in epithelial cadherin (E-cadherin) expression and functions are associated to BC, but the underlying molecular mechanisms have not been fully elucidated. We have previously reported a novel human E-cadherin splice variant (E-cadherin variant) mRNA.

E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness.

Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process.

Identification of a Novel Human E-Cadherin Splice Variant and Assessment of Its Effects Upon EMT-Related Events.

Epithelial Cadherin (E-cadherin) is involved in calcium-dependent cell-cell adhesion and signal transduction. The E-cadherin decrease/loss is a hallmark of Epithelial to Mesenchymal Transition (EMT), a key event in tumor progression. The underlying molecular mechanisms that trigger E-cadherin loss and consequent EMT have not been completely elucidated.

CDH1/E-cadherin and solid tumors. An updated gene-disease association analysis using bioinformatics tools.

Cancer is a group of diseases that causes millions of deaths worldwide. Among cancers, Solid Tumors (ST) stand-out due to their high incidence and mortality rates. Disruption of cell-cell adhesion is highly relevant during tumor progression.

Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E-cadherin, induces β-catenin re-localisation and triggers apoptosis-related events in breast cancer cells.

Background Information: Epithelial cadherin (E-cadherin) is involved in cell-cell adhesion through its extracellular domain, whereas the intracellular domain interacts with adaptor proteins, i.e. β-catenin, links E-cadherin to the actin cytoskeleton and participates in signal transduction events.