Unique miRNA Expression Profile in MSI- and EMAST-Unstable Sporadic Colon Cancer.

MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide repeats (MSS/EMAST-H), and high microsatellite unstable (MSI-H/EMAST-H) tumor subgroups as well as in tumors with different clinicopathologic characteristics. An RT-qPCR analysis of miRNA expression was carried out on 45 colon cancer and adjacent normal tissue samples (15 of each group).

Association of Functional Polymorphisms in and Pathway Genes with Different Types of Microsatellite Instability in Sporadic Colorectal Cancer.

Microsatellite instability (MSI) has been recognized as an important factor in colorectal cancer (CRC). It arises due to deficient mismatch repair (MMR), mostly attributed to MLH1 and MSH2 loss of function leading to a global MMR defect affecting mononucleotide and longer microsatellite loci. Recently, microsatellite instability at tetranucleotide loci, independent of the global MMR defect context, has been suggested to represent a distinct entity with possibly different consequences for tumorigenesis.

EMAST Type of Microsatellite Instability-A Distinct Entity or Blurred Overlap between Stable and MSI Tumors.

Microsatellite instability (MSI) represents an accumulation of frameshifts in short tandem repeats, microsatellites, across the genome due to defective DNA mismatch repair (dMMR). MSI has been associated with distinct clinical, histological, and molecular features of tumors and has proven its prognostic and therapeutic value in different types of cancer. Recently, another type of microsatellite instability named elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been reported across many different tumors.

Analysis of polymorphisms in EGF, EGFR and HER2 genes in pancreatic neuroendocrine tumors (PNETs).

Objectives: Pancreatic neuroendocrine tumors (NETs) are rare and account for about 7% of all cancers occurring in the pancreas. The epidermal growth factor family of receptors and their ligands play an important role in the growth and progression of tumors but their role in PNET development remains unknown. We hypothesized that functional single nucleotide polymorphisms (SNPs) in the EGF, EGFR, and HER2 genes might affect individual susceptibility to PNETs development and invasion like it was shown for various other tumors.

Regulation of KRAS protein expression by miR-544a and KRAS-LCS6 polymorphism in wild-type KRAS sporadic colon adenocarcinoma.

Colorectal carcinoma (CRC) results from the accumulation of genetic mutations and alterations in signaling pathways. KRAS is mutated in 40% of CRC cases and is involved in increased tumor cells proliferation and survival. Although KRAS mutations are a dominant event in CRC tumorigenesis, increased wild-type KRAS expression has a similar effect on accelerated tumor growth.

Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer.

Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the gene that can modulate transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for CA-SSR1 polymorphism and MSI status.

Inflammation-related cytokines and their roles in gastroenteropancreatic neuroendocrine neoplasms.

Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

Objective: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.

Design: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA.

Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma.

Background/aim: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression.

Analysis of Loss of Heterozygosity, Expression, and IVS10+12G>A Polymorphism in Sporadic Colon Cancer.

Background: mutS homolog 2 (MSH2) deficiency may be involved in the development of microsatellite instability found in certain sporadic colorectal tumors. In addition to mutations or loss of heterozygosity resulting in complete loss of MSH2 function, polymorphisms affecting MSH2 expression have been also identified. Therefore, the aim of this study was to examine MSH2 status in sporadic colon cancer.

Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2.

Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68).

High VEGF serum values are associated with locoregional spread of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascularized neoplasms, capable of synthethisizing VEGF-A, a key mediator of angiogenesis. In pancreatic neuroendocrine tumors (pNETs) VEGF expression is higher in benign and low-grade tumors and associated with good prognosis (neuroendocrine paradox) while the VEGF role in gastrointestinal NETs (GI-NETs) is still unclear. In this study, we examined the VEGF-1154A/G polymorphism in 145 GEP-NET patients and 150 controls.

COX-1 and COX-2 polymorphisms in susceptibility to cerebral palsy in very preterm infants.

Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain. Recent epidemiological and clinical data suggest intrauterine infection/inflammation as the most common cause of preterm delivery and neonatal complications, including CP. Cyclooxygenases are key enzymes in the conversion of arachidonic acid to prostaglandins.

Single nucleotide polymorphism of toll-like receptor 4 (TLR4) is associated with juvenile spondyloarthritis in Croatian population.

Single nucleotide polymorphisms (SNP) of toll-like and NOD-like receptors have been associated with altered receptor activity and modified production of proinflammatory cytokines leading to a number of diseases. Our aim was to determine whether SNP of TLR2 (Arg753Gln), TLR4 (Asp299Gly, Thr399Ile), and NLRP3 (Q705K) influence susceptibility to juvenile spondyloarthrtis (jSpA) and juvenile idiopathic arthritis (JIA). After the DNA extraction, 26 patients with jSpA, 11 with oligoarticular, polyarticular, or systemic JIA, and 40 healthy controls were genotyped for Arg753Gln, Asp299Gly, Thr399Ile, and Q705K SNP using real-time PCR-SNP analysis.

Mononucleotide repeats in the SMAD4 gene promoter in colon carcinoma tissue of Croatian patients.

This study was aimed at the analysis of mononucleotide repeats -462T(15) and -4T(12) in the SMAD4 gene promoter in sporadic colon adenocarcinoma tissue of Croatian patients. The analysis has included 60 pairs of samples of colon tumor and adjacent normal tissue. The number of thymidines in the tracts -462T(15) and -4T(12) of the SMAD4 gene promoter was determined by PCR with fluorescently labeled primers followed by the analysis of obtained DNA fragments by capillary electrophoresis.

TNFα gene/protein in tumorigenesis of sporadic colon adenocarcinoma.

Purpose: Inherited polymorphisms in immunomodulatory genes such as cytokines may contribute to variation in immunological response and genetic susceptibility for complex diseases, including cancer. TNFα can mediate tumor progression by inducing proliferation, invasion and metastasis of tumor cells. The aim of our study was to examine the allelic frequencies of TNFα promoter SNPs, -1031 T/C, -857 C/T, -308 G/A and -238 G/A, in patients with sporadic colon adenocarcinoma in order to investigate the possible role of these SNPs in susceptibility to sporadic colon cancer.

New insights into the role of chronic inflammation and cytokines in the etiopathogenesis of gastroenteropancreatic neuroendocrine tumors.

Although previously considered rare, recent epidemiological studies have revealed that the incidence (3.6/100,000) and prevalence (35/100,000) of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the past few decades. Despite the progress in the understanding of GEP-NET molecular biology, there is still little advance in the early diagnosis due to lack of specific tumor markers.

Reduced FHIT expression is associated with tumor progression in sporadic colon adenocarcinoma.

Purpose: Tumor supressor gene FHIT was identified at chromosome 3p14.2 spanning the FRA3B fragile site and is very often inactivated in different types of cancer. The aim of this study was to examine the frequency of FHIT gene LOH as well as FHIT mRNA and protein expression in sporadic colon adenocarcinoma.

Loss of NF2/Merlin expression in advanced sporadic colorectal cancer.

Purpose: NF2/Merlin was first identified through its association with neurofibromatosis type 2 (NF2). However, accumulating evidence suggests a more general involvement in tumorigenesis and, in particular, a broader role in tumor suppression. The aim of this study was to examine NF2/Merlin involvement in sporadic colorectal cancer.

P2RY12 gene polymorphisms and effect of clopidogrel on platelet aggregation.

Objective of this study was to assess platelet response to clopidogrel and its association with certain single nucleotide polymorphisms (SNPs) of the P2RY12 gene. Several studies have shown that patients with poor in vitro response to clopidogrel have worse outcomes after coronary interventions. Pharmacological response to clopidogrel is mediated by the P2Y12 platelet receptor, therefore, SNPs of the P2RY12 gene may account for some of the observed variability in the cardiovascular risk.

miR-106a overexpression and pRB downregulation in sporadic colorectal cancer.

Rb1 plays an important role in cell cycle progression and therefore may be involved in malignant transformation of colonic cells. The aim of our research was to define the potential role of Rb1 as a prognostic biomarker in tumorigenesis of sporadic colorectal cancer, and to examine the role of miR-106a in Rb1 regulation as it functionally binds to 3'UTR of transcribed mRNA. We examined LOH and promoter methylation status.

Even stressed cells are individuals: second messengers of free radicals in pathophysiology of cancer.

Pathophysiological processes associated with disturbances in cell and tissue oxidative homeostasis, are associated with self-catalyzed process of lipid peroxidation. The end products of lipid peroxidation are reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), acting as "second messengers of free radicals." Although reactive aldehydes were first recognized only as cytotoxic, new evidence has come to light, related to their cell growth regulatory functions achieved through cell signaling.

Decrease in circulating DNA, IL-10 and BAFF levels in newly-diagnosed SLE patients after corticosteroid and chloroquine treatment.

Arsenal of pattern-recognition receptors alongside antibody production machinery make B cells vulnerable to autoimmune response if an autoantigen elicits both pathways in a self-sustained fashion. Systemic lupus erythematosus is an autoimmune disease characterized by autoantibodies to DNA, RNA and related structures. Murine studies demonstrated autoreactive B cell activation upon TLR9 stimulation with DNA-containing immune complexes.