Inter-Tissue and Intra-Tissue Co-Expression Networks in Human Metabolism: Morphological Evaluation of the Link Between Transcription Factors ERβ and NFAT in Morbid Obesity.

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive "cross-talk" with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2).

Introduction: Our study is an "in situ" morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored.

SRC-3/AIB-1 may Enhance Hepatic NFATC1 Transcription and Mediate Inflammation in a Tissue-Specific Manner in Morbid Obesity.

Background: Obesity is a global epidemic which is associated with several cardiometabolic comorbidities and is characterized by chronic, low grade systemic inflammation. Numerous biomarkers have been implicated in the pathophysiology of the disease, including transcription factors and coregulators. Steroid Receptor Coactivator (SRC)-family represent the master regulators of metabolic pathways and their dysregulation is strongly associated with numerous metabolic disorders.

Can obesity-induced inflammation in skeletal muscle and intramuscular adipose tissue accurately detect liver fibrosis?

Objectives: Obesity is characterized by a chronic, low grade, systemic inflammation. However, little is known about the role of skeletal muscle, which represents an active metabolic organ whose activities need to be determined. The purpose of our study was to detect relationships between skeletal muscle and adipose tissue inflammation with nonalcoholic fatty liver disease (NAFLD) and diabetes, as well as to explore associations with clinicopathological parameters.

Inter-tissue expression patterns of the key metabolic biomarker PGC-1α in severely obese individuals: Implication in obesity-induced disease.

Objective: PGC-1α is already known as a significant regulator of mitochondrial biogenesis, oxidative phosphorylation and fatty acid metabolism. Our study focuses on the role of PGC1α in morbid obesity, in five different tissues, collected from 50 severely obese patients during planned bariatric surgery.

Methods: The investigated tissues included subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver.

Epigenetic modifications in cutaneous malignant melanoma: EZH2, H3K4me2, and H3K27me3 immunohistochemical expression is enhanced at the invasion front of the tumor.

Cancer stem cells and the misregulation of epigenetic modifications have been identified to possess a determinative role in carcinogenesis. The purpose of this study was to investigate the expression profile of EZH2 and H3K4me2 and H3K27me3, which constitute stem cell-like "bivalent" domains, in cutaneous malignant melanoma. A comparative analysis of their immunohistochemical expression between the invasion front (IF) and the inner tumor mass was also evaluated.

Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and worse patient prognosis.

Estrogen receptors alpha (ERα) and beta (ERβ) and their co-regulatory proteins are key components of complex signaling networks that specifically regulate the growth and development of various tissues and tumors. Still, their protein expression profiles and possible role in the pathogenesis of astrocytic tumors remain largely unknown. The purpose of the present study is to evaluate the differential protein expression of ΕRα, ERβ, and their co-activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health Organization (WHO) grade II-IV, using immunohistochemistry.

Expression of ERβ and its co-regulators p300 and NCoR in human transitional cell bladder cancer.

Objective: Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-β (ERβ). We study the expression of ERβ and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer.

Patients And Methods: One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study.

Coordinated increased expression of Cyclooxygenase2 and nuclear factor κB is a steady feature of urinary bladder carcinogenesis.

Objectives: The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-κB immunohistochemical expression in a large series of normal epithelium and bladder carcinomas.

Methods: Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas).

Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.

Objectives: To investigate the expression of nuclear factor-kappaB (NF-kappaB) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis.

Methods: Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappaB, and tumor grade and T-stage were evaluated, along with demographic data, sex and age.

Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression.

Objectives/hypothesis: Invasive squamous cell carcinomas (SCC) of the larynx, like most solid tumors, are surrounded by a reactive stroma, in which cancer associated fibroblasts (CAFs) are the predominant cell type. This mesenchymal reaction may affect cancer progression multiply. The proinflammatory enzyme cyclooxygenase-2 (COX-2) has been correlated with head and neck cancer.

Expression of ERalpha, ERbeta and co-regulator PELP1/MNAR in colorectal cancer: prognostic significance and clinicopathologic correlations.

Background: Estrogen receptor beta (ERbeta) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. ER novel co-regulator, proline-, glutamic acid- and leucine-rich protein 1 (PELP1/MNAR) has been characterized, but its expression in colorectal carcinomas has not been investigated.

Methods: ERalpha, ERbeta and PELP1/MNAR protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas and adenocarcinomas from 113 patients with colorectal cancer.

Retinoid X receptor overexpression desensitizes laryngeal epithelium to carcinogenic effects associated with epidermal growth factor receptor upregulation.

Objective: Squamous cell carcinomas (SCCs) of the larynx are sequelae of hyperplastic and dysplastic lesions. Epidermal growth factor receptor (EGFR) is found frequently overexpressed in SCCs of the head and neck, although its regulatory role is not fully elucidated. Conversely, retinoid X receptor alpha (RXRalpha) mediates the reversing effects of retinoids on head and neck carcinogenesis.

Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression.

Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERbeta). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERalpha, ERbeta1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry.

Estrogen receptor alpha/beta, AIB1, and TIF2 in colorectal carcinogenesis: do coregulators have prognostic significance?

Purpose: Estrogen receptor beta (ER beta) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. Estrogen receptor coregulators, amplified in breast cancer 1 (AIB1) and transcription intermediary factor 2 (TIF2), have been well-characterized, but their expression in colorectal carcinomas has not been investigated.

Materials And Methods: Estrogen receptor alpha (ER alpha), ER beta, AIB1, and TIF2 protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas, and adenocarcinomas from 110 patients with colorectal cancer.

Expression of estrogen receptor co-regulators NCoR and PELP1 in epithelial cells and myofibroblasts of colorectal carcinomas: cytoplasmic translocation of NCoR in epithelial cells correlates with better [corrected] prognosis.

Proline-, glutamic acid-, and leukine-rich protein (PELP1) is a novel co-regulatory protein that modulates genomic and non genomic actions of estrogen receptors. Nuclear receptor co-repressor (NCoR) represses estrogen-receptor-dependent transcription. PELP1 and NCoR expression was evaluated in tissue sections from 107 formalin-fixed, paraffin-embedded colectomy specimens.

EGF-R is expressed and AP-1 and NF-kappaB are activated in stromal myofibroblasts surrounding colon adenocarcinomas paralleling expression of COX-2 and VEGF.

Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-kappaB transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-kappaB, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells.

Peroxisome proliferator-activated receptor gamma expression correlates with the differentiation level of normal, premalignant, and malignant laryngeal squamous cells.

Objective: Peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in the differentiation of several cell types, such as adipocytes, monocytes, and epidermal keratinocytes. This study concentrated on PPAR gamma's potential role in the maturation process of laryngeal squamous epithelium, both normal and premalignant, as well as in the differentiation grade of squamous cell carcinomas (SCCs) of the larynx.

Design: A retrospective study.

HER-3 in colorectal tumourigenesis: from mRNA levels through protein status to clinicopathologic relationships.

Introduction: Colorectal cancer is a major cause of cancer mortality in the Western world. Although HER-3 signalling is known to be implicated in colorectal carcinogenesis, the significance of its expression, localisation and phosphorylation remains elusive.

Methods: Quantitative RT-PCR for HER-3 mRNA and immunohistochemistry for HER-3 and phosphorylated HER-3 (pHER-3) protein were performed in normal tissue, adenomas and carcinomas from 140 patients with colorectal cancer.

Glottic versus supraglottic tumors: differential molecular profile.

Glottis and supraglottis, although anatomically interconnected, are embryologically distinct. Moreover, squamous cell carcinomas arising from these subsites, differ in terms of epidemiology, risk factors, clinical behaviour and prognosis. This study aims to explore any possible differences between their molecular profiles.

Coordinated upregulation of COX-2 and NF-kappaB is a steady feature of laryngeal carcinogenesis.

Background/aims: Laryngeal cancer is the endpoint of a multistage process involving hyperplastic and dysplastic lesions, not adequately defined in their molecular aspect. Our objective was to evaluate the expression of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) and the chief transcription factor nuclear factor-kappaB (NF-kappaB) in laryngeal carcinomas and their precursors, as well as to explore any association between the two molecules.

Methods: We performed paraffin section immunohistochemistry for COX-2 and the p65 subunit of NF-kappaB, in tissues from 129 patients with tumors or premalignancies.

NF-kappaB/PPAR gamma and/or AP-1/PPAR gamma 'on/off' switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression.

Background And Aims: Several studies indicate that peroxisome proliferator-activated receptor gamma (PPAR gamma) represses activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB) transcriptional activity and this negative cross-talk occupies an important role in carcinogenesis. The present study evaluated the differential expression profile of AP-1 constituents (c-FOS and phosphorylated-active pc-JUN), p-I kappaB-alpha (phosphorylated I kappaB-alpha, a signaling intermediate of NF-kappaB pathway), PPAR gamma, cyclic AMP-response element binding-binding protein (CBP, a known AP-1, NF-kappaB, and PPAR gamma transcriptional coactivator), epidermal growth factor receptor (EGF-R), p53, and COX-2 in normal colonic epithelial cells and colon adenocarcinoma cells.

Materials And Methods: Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from 60 patients with colon adenocarcinomas.

PPAR-gamma is expressed and NF-kB pathway is activated and correlates positively with COX-2 expression in stromal myofibroblasts surrounding colon adenocarcinomas.

Purpose: Accumulated evidence indicates that carcinogenesis is closely associated with the transformation of normal stroma into a 'reactive' stromal phenotype. The present study investigated the role of PPARgamma, COX-2 and p-IkB-alpha--important molecular targets of colon cancer chemoprevention--in this stromal remodeling by evaluating and comparing the expression of these factors in stromal myofibroblasts, macrophages and endothelial cells that surround normal colonic mucosa and colon cancer.

Methods: Immunohistochemical methodology was employed on archived paraffin-embedded sections prepared from tumors and adjacent normal colon from 45 patients with colon adenocarcinomas.

Retinoid-X-receptor alpha (RXRalpha) expression during laryngeal carcinogenesis: detrimental or beneficial event?

RXRalpha is an obligatory heterodimerization partner in many signal transducing pathways. To evaluate RXRalpha expression during laryngeal carcinogenesis, immunohistochemistry was performed on laryngeal epithelial specimens of 154 patients with normal-appearing, hyperplastic, dysplastic laryngeal epithelium and squamous cell carcinoma. RXRalpha up-regulation was detected from the early stages of laryngeal carcinogenesis compared with normal epithelium.