MicroRNAs in Colorectal Cancer Drug Resistance: Shooters become Targets

Copyright: © 2013 Fanale D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. MicroRNAs (MiRNAs) are involved in the regulation of several biological processes such as development, differentiation, metabolism, apoptosis and proliferation. Recently, it has been shown that deregulated expression of miRNAs are present in different human cancers, suggesting a potential role in carcinogenesis [1,2]. Recent evidence suggests that miRNAs may represent potential new therapeutic approaches in patients with dru…

Leptin plasma levels in patients undergoing prostate biopsy. a preliminary study in 50 patients

Introduction/Aim: To reduce the number of negative prostate biopsies and to detect clinical significant prostate tumors in patients with elevated serum PSA represent major challenges in urological oncology. Prostate tumors diagnosed in patients with elevated Body Mass Index (BMI) show higher Gleason score and more aggressive biological behavior than those diagnosed in normal population (1). Elevated plasma levels of leptin and other adipose tissue derived factors (adipokines), are evident in obese men (2). Many studies have investigated the role of leptin as a putative molecular mediator between obesity and prostate cancer with contradictory results. Also in normal or overweight (BMI <30) m…

Liquid Biopsy in Breast Cancer

Breast cancer (BC) to date remains the most common cancer in women. Nowadays, BC is often diagnosed at local disease stage, and, after surgery, based on individual’s risk of relapse, the patients undergo adjuvant systemic treatment to decrease the risk of recurrence. Current BC classification and assessment remain strongly based on clinicopathological criteria, including patient age, tumor size, lymph node invasion, histological type, and grade. According to standard practice, the choice of treatment strategy includes assays for estrogen (ER) and progesterone (PgR) receptor expression levels, overexpression of human epidermal growth factor receptor 2 (Her-2), or amplification status of the …

La chora Salinon nell'agiografia storica italo-greca

The Interplay between Metabolism, PPAR Signaling Pathway, and Cancer

High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression

Tryptase(+) mast cells (MCs), abundant in the invasive front of tumours, contribute to tissue remodelling. Indeed, protease-activated receptor- 2 (PAR-2) activation by MC-tryptase is considered an oncogenic event in colorectal cancer (CRC). Recently, we have suggested NHERF1 as a potential new marker in CRC. In this study, we aimed to determine the distribution of tryptase(+) MCs and PAR-2 and to examine the relationship between PAR-2 and NHERF1, investigating their reputed usefulness as tumour markers. We studied a cohort of 115 CRC specimens including primary cancer (C) and adjacent normal mucosa (NM) by immunohistochemical double staining, analyzing the protein expression of MC-tryptase,…

Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma

Background & Aims Alterations of individual genes variably affect the development of hepatocellular carcinoma (HCC). Thus, we aimed to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRNs). Methods Using data from The Cancer Genome Atlas, from the LIRI-JP (Liver Cancer – RIKEN, JP project), and from our transcriptomic, transfection and mouse transgenic experiments, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of β-catenin (CTNNB1). We further generated and validated a quantitative mathematical model of the GRN using human cell lines and in vivo expression data. Results We found that LIN28B and C…

Plasma levels of angiogenetic markers in men candidate to prostate biopsy

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Abstract: The diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug. In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role. The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to…

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyz…

Hypoxia and Human Genome Stability: Downregulation of BRCA2 Expression in Breast Cancer Cell Lines

Previously, it has been reported that hypoxia causes increased mutagenesis and alteration in DNA repair mechanisms. In 2005, an interesting study showed that hypoxia-induced decreases in BRCA1 expression and the consequent suppression of homologous recombination may lead to genetic instability. However, nothing is yet known about the involvement of BRCA2 in hypoxic conditions in breast cancer. Initially, a cell proliferation assay allowed us to hypothesize that hypoxia could negatively regulate the breast cancer cell growth in short term in vitro studies. Subsequently, we analyzed gene expression in breast cancer cell lines exposed to hypoxic condition by microarray analysis. Interestingly,…

Oncogene Addiction in Solid Tumors

The term “oncogenic addiction” refers to the phenomenon by which tumor cells become completely dependent on a single pathway, derived from the activation of a specific oncogene, for their survival and proliferation. The clinical relevance of oncogene addiction paradigm is highlighted by a growing number of examples that demonstrate the efficacy of several therapeutic agents that target specific oncogenes in various cancer types. This chapter aims to summarize the recent evidences concerning the concept of oncogene addiction and describes molecular mechanisms that could explain this phenomenon.

Correlation between leptin plasmatic levels in non-obese patients and detection rate at prostate biopsy”- Poster P147

Serum levels of angiogenetic cancer biomarkers in men undergoing prostate biopsy. Preliminary data

Background: The reduction of the number of negative prostate biopsies in patients with elevated serum PSA represents a major challenge. Several angiogenetic biomarkers are involved in carcinogenesis and cancer progression. The aim of our preliminary study was to investigate if their serum levels might be related to prostate cancer detection. Patients and Methods: Angiopoietin 2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF- BB, PECAM-1, VEGF, PTH were the selected biomarkers for our research. They were measured by BioPlex immunoassay. As a preliminary step, consecutive unselected patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels were entered. A 12-co…

Uno sguardo da Bisanzio

Si passano in rassegna le testimonianze bizantine dei secoli IV e V sulla Sicilia, quelle - in particolare - relative alla problematica dei rapporti fra Cristianesimo e Paganesimo, da cui emerge un radicamento relativamente tardivo della organizzazione ecclesiastica cristiana in Sicilia.

THE ROLE OF INTRAVESICAL GLYCOSAMINOGLYCANS IN TOXICITY INDUCED BY ADJUVANT INTRAVESICAL THERAPY: GENETIC LABORATORY EVIDENCE

Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles.

Abstract Background Virtually all cell types have the capacity to secrete nanometer-sized extracellular vesicles, which have emerged in recent years as potent signal transducers and cell-cell communicators. The multifunctional protein Alix is a bona fide exosomal regulator and skeletal muscle cells can release Alix-positive nano-sized extracellular vesicles, offering a new paradigm for understanding how myofibers communicate within skeletal muscle and with other organs. S-palmitoylation is a reversible lipid post-translational modification, involved in different biological processes, such as the trafficking of membrane proteins, achievement of stable protein conformations, and stabilization…

Politica gregoriana, latinizzazione della religiosità bizantina in Italia meridionale, isole di resistenza greca nel mezzogiorno d'Italia tra Xi e XII secolo

Ripercorrendo le tappe dell'azione politica di papa Gregorio VII, con speciale riguardo ai rapporti con l'Impero romano-bizantino e con i Normanni d'Italia meridionale, vengono richiamate le fasi salienti della latinizzazione, talora forzosa, quando non violenta, delle chiese e dei monasteri greci di quell'area geografica.

Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?

Abstract: Objective: miRNAs are attractive molecules for cancer treatment, including colon rectal cancer (CRC). We investigate on the molecular mechanism by which miR-182 could regulate thrombospondin-1 (TSP-1) expression, a protein down-regulated in CRC and inversely correlated with tumor vascularity and metastasis. Background: MicroRNAs are small non-coding RNAs that regulate the expression of different genes, involved in cancer progression, angiogenesis and metastasis. miR-182, over-expressed in colorectal cancer (CRC), has like predictive target thrombospondin-1 (TSP-1), a protein inversely correlated with tumor vascularity and metastasis that results downregulated in different types of…

Studio pilota sul valore predittivo dei livelli plasmatici di 9 fattori angiogenetici nella selezione di pazienti candidati alla biopsia prostatica

To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients' selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A potent…

VISCERAL FAT TISSUE ACTIVITY DOES NOT CORRELATE TO HIGH GRADE PROSTATE CANCER RISK AT BIOPSY

miRNAs in the metaplastic transformation of the esophagus: something in the way toward carcinogenesis.

Background: Barrett's esophagus (BE) is a precancerous lesion that predisposes to development of esophageal adenocarcinoma (EAC) and it is associated with gastroesophageal reflux disease. Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett’s metaplasia and adenocarcinoma are almost unknown and there is an increasing interest in the developing of more objective biomarkers that can improve risk prediction. Several evidences suggest that some miRNAs are differentially expressed in the BE and EAC. Among them, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in the metaplasia and in neoplastic progression. Aim: The …

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequ…

S. Luca da Dèmena crociato ante litteram e l'epopea "agìaca" antisaracena italo-greca

Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.

The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…

Tra scienza e ideologia. Medicina e taumaturgia nell'agiografia storica italo-greca

Monokeros estin outos, zoon autonomon. Sesso, santità, potere nel Bìos di Nilo da Rossano

Dal rapporto con l'altro sesso, con la santità e col potere nelle sue varie forme, viene messo in rilievo l'atteggiamento, si direbbe "anarchico", di Nilo da Rossano, teso sempre alla ricerca della libertà fino alla morte.

Pilot Study on Predictive Value of Plasmatic Levels of 9 Angiogenetic Biomarkers in Selection of Patients Candidate to Prostate Biopsy

To reduce the number of negative prostate biopsies in patients with elevated PSA serum levels represents a major challenge in urological oncology. Angiogenetic factors might be involved in initial stages of prostate cancer and might represent useful tools in patients’ selection for prostate biopsy. The plasmatic levels of Angiopoietin-2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF were measured by BioPlex immunoassay in patients undergoing prostate biopsy for palpable prostate nodule and/or elevated PSA levels (≥4 ng/mL). They were related with biopsy results. ROC curve analysis was exploited to test the diagnostic accuracy of each biomarker by AUC calculation. A poten…

Abstract 448: Molecular analysis of BRAF gene and PTEN gene expression in metastatic colorectal cancer patients: Feasibility study

Abstract Introduction There are numerous causes triggering CRC. 25-80% of CRC shown a deregulation in Epidermal Growth Factor Receptor (EGFR) pathway. Two signaling pathways downstream of the EGFR are dysregulated in CRC the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3-kinase (PI3K) pathway. Activating mutations in KRAS and BRAF (MAPK pathway) and PIK3CA affect prognosis and/or response to anti-EGFR MoAb. PTEN is a downstream effector of EGFR pathway and is involved in PI3K pathway. Loss of PTEN protein expression can occur through epigenetic silencing and mutation or allelic loss. Immunohistochemistry (IHC) is the most effective way to assay for loss of PTEN expressio…

HIF-1 is involved in the negative regulation of AURKA expression in breast cancer cell lines under hypoxic conditions

Numerous microarray-based gene expression studies performed on several types of solid tumors revealed significant changes in key genes involved in progression and regulation of the cell cycle, including AURKA that is known to be overexpressed in many types of human malignancies. Tumor hypoxia is associated with poor prognosis in several cancer types, including breast cancer (BC). Since hypoxia is a condition that influences the expression of many genes involved in tumorigenesis, proliferation, and cell cycle regulation, we performed a microarray-based gene expression analysis in order to identify differentially expressed genes in BC cell lines exposed to hypoxia. This analysis showed that h…

MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?

Recently, the hypothesis that colorectal tumors originate from a subpopulation of cells called ‘cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit stem-like features, has been confirmed experimentally in various human cancers. Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have demonstrated that this rare cell population can be isolated by the expression of specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are crucial for post-transcriptional regulation of gene expression and participate in a wide variety of biological functions, including development, cell proliferation, differentiation, metabolism…

Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells

Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear. As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells tre…

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

The angiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulating angiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipid metabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasma triglycerides (TG) and fatty acids. Subsequently, ANGPTL4 has been shown to be involved in several nonmetabolic and metabolic conditions, both physiological and pathological, including …