Detection and Quantification of Calcitonin Gene-Related Peptide (CGRP) in Human Plasma Using a Modified Enzyme-Linked Immunosorbent Assay.

Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide that plays a putative role in the pathophysiology of migraine headaches and may be a candidate for biomarker status. CGRP is released from neuronal fibers upon activation and induces sterile neurogenic inflammation and arterial vasodilation in the vasculature that receives trigeminal efferent innervation. The presence of CGRP in the peripheral vasculature has spurred investigations to detect and quantify this neuropeptide in human plasma using proteomic assays, such as the enzyme-linked immunosorbent assay (ELISA).

High-risk HPV infection-associated hypermethylated genes in oropharyngeal squamous cell carcinomas.

Background: HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are sensitive to chemo-radiation therapy and have favorable survival outcomes compared with HPV-negative cancers. These tumors are usually not related to tobacco and alcohol exposure. Therefore, diagnosing HPV-positive OPSCCs for the appropriate disease management is crucial, and no suitable markers are available for detecting early malignancies in HPV-infected tissues.

Clinical and Prognostic Significance of the Eighth Edition Oral Cancer Staging System.

Objectives: The most notable changes in the eighth edition of the AJCC Cancer Staging System include incorporating the depth of invasion (DOI) into T staging and extranodal extension (ENE) into N staging. In this study, we retrospectively assessed the prognostic and clinical implications of the eighth TNM staging system. Materials and Methods: Patients with Oral Squamous Cell Carcinoma (OSCC) who were treated surgically between 2010 and 2017 were retrospectively reviewed.

GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma.

Disruption of the KEAP1-NRF2 pathway results in the transactivation of NRF2 target genes, consequently inducing cell proliferation and other phenotypic changes in cancer cells. Here, we demonstrated that GULP1 was a KEAP1-binding protein that maintained actin cytoskeleton architecture and helped KEAP1 to sequester NRF2 in the cytoplasm. In urothelial carcinoma of the bladder (UCB), silencing of GULP1 facilitated the nuclear accumulation of NRF2, led to constitutive activation of NRF2 signaling, and conferred resistance to the platinum drug cisplatin.

Multidisciplinary model for hospital-territory integrated management of patient with bone fragility: primary and secondary prevention of fractures according to severity and complexity.

The aim of this study was to promote the construction of a real network and a shared diagnostic and therapeutic management model between hospitals and out-of-hospital healthcare services to capture as many patients with bone fragility as possible. Starting from the analysis of the clinical competences present in the province of Pavia, the bone specialists (BSs) organized some educational events involving both general practitioners (GPs) and hospital specialists. The Fracture Liaison Service (FLS) model, the revision of Note 79, the national plan for chronicity and the health reform of the Lombardy Regional Authority supported the structure of our model, in which the roles of clinicians are well defined and based on the complexity and severity of patients.

Repurposing the FDA-Approved Antiviral Drug Ribavirin as Targeted Therapy for Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma with a proclivity for systemic dissemination, leading many patients to present with advanced stage disease and fail available treatments. There is a notable lack of targeted therapies for NPC, despite working knowledge of multiple proteins with integral roles in NPC cancer biology. These proteins include EZH2, Snail, eIF4E, and IMPDH, which are all overexpressed in NPC and correlated with poor prognosis.

Tissue and Cell-Free DNA-Based Epigenomic Approaches for Cancer Detection.

Background: Over 9 million people die of cancer each year worldwide, reflecting the unmet need for effective biomarkers for both cancer diagnosis and prognosis. Cancer diagnosis is complex because the majority of malignant tumors present with long periods of latency and lack of clinical presentation at early stages. During carcinogenesis, premalignant cells experience changes in their epigenetic landscapes, such as differential DNA methylation, histone modifications, nucleosome positioning, and higher orders of chromatin changes that confer growth advantage and contribute to determining the biologic phenotype of human cancers.

Integrated transcriptomic and epigenomic analysis of ovarian cancer reveals epigenetically silenced GULP1.

Many epigenetically inactivated genes involved in ovarian cancer (OC) development and progression remain to be identified. In this study we undertook an integrated approach that consisted of identification of genome-wide expression patterns of primary OC samples and normal ovarian surface epithelium along with a pharmacologic unmasking strategy using 3 OC and 3 immortalized normal ovarian epithelial cell lines. Our filtering scheme identified 43 OC specific methylated genes and among the 5 top candidates (GULP1, CLIP4, BAMBI, NT5E, TGFβ2), we performed extended studies of GULP1.

Tobacco and alcohol-induced epigenetic changes in oral carcinoma.

Purpose Of Review: The present review aims to describe the epigenetic alterations observed in oral cancer linked to the exposure to alcohol and/or tobacco.

Recent Findings: Recent findings emphasize the importance of epigenetics in oral cancer progression and in how risk factors (as tobacco and alcohol) affect the basal epigenetic profiles. Deeper techniques and detailed approaches allowed the perception that individual CG changes and even subtle changes may represent important epigenetic alterations resulting in expression changes and other carcinogenic consequences.

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. A methylation panel of 6 genes (, and ) was selected from TCGA dataset.

Expression of GULP1 in bronchial epithelium is associated with the progression of emphysema in chronic obstructive pulmonary disease.

Background: GULP1 functions as a cytoplasmic adaptor protein involved in the engulfment of apoptotic cells. The aim of this study was to investigate the expression and/or promoter methylation of GULP1 in the bronchial tissue and the lung parenchyma of chronic obstructive pulmonary disease (COPD) patients and control subjects without COPD (non-smokers and smokers).

Methods: Using a case-control design, we selected a group of 15 subjects with non-small cell lung carcinoma (NSCLC), 15 subjects with COPD, 9 subjects of without COPD (4 non-smokers and 5 smokers) as controls.

Promoter methylation of MCAM, ERα and ERβ in serum of early stage prostate cancer patients.

Background: Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.

Comparative mutational landscape analysis of patient-derived tumour xenografts.

Background: Screening of patients for cancer-driving mutations is now used for cancer prognosis, remission scoring and treatment selection. Although recently emerged targeted next-generation sequencing-based approaches offer promising diagnostic capabilities, there are still limitations. There is a pressing clinical need for a well-validated, rapid, cost-effective mutation profiling system in patient specimens.

Adenoid cystic carcinoma: emerging role of translocations and gene fusions.

Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized.

Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening.

Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2'-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice.

High-performance detection of somatic D-loop mutation in urothelial cell carcinoma patients by polymorphism ratio sequencing.

Unlabelled: Utilizing a polymorphism ratio sequencing platform, we performed a complete somatic mutation analysis of the mitochondrial D-loop region in 14 urothelial cell carcinomas. A total of 28 somatic mutations, all heteroplasmic, were detected in 8 of 14 individuals (57.1 %).

Epigenetic screening of salivary gland mucoepidermoid carcinoma identifies hypomethylation of CLIC3 as a common alteration.

Objectives: The role of promoter methylation in the development of mucoepidermoid carcinoma (MEC) has not been fully explored. In this study, we investigated the epigenetic landscape of MEC.

Methods: The Illumina HumanMethylation27 BeadChip array and differential methylation analysis were utilized to screen for epigenetic alterations in 14 primary MEC tumors and 14 matched normal samples.

Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA.

Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as atypical adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and fully invasive adenocarcinoma. Despite efforts to identify predictive markers of malignant transformation, alterations driving this progression are poorly understood.

An integrated genome-wide approach to discover deregulated microRNAs in non-small cell lung cancer: Clinical significance of miR-23b-3p deregulation.

In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes.

Epigenetic silencing of S100A2 in bladder and head and neck cancers.

S100A2, a member of the S100 protein family, is known to be downregulated in a number of human cancers, leading to its designation as a potential tumor suppressor gene. Here, we investigated the expression and methylation status of S100A2 in head&neck and bladder cancer. Reduced mRNA and protein expression was observed in 8 head&neck and bladder cancer cell lines.

Milk derived colloid as a novel drug delivery carrier for breast cancer.

Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component 'MDC' from milk-derived colloid.

Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue.

Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.

Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic.