Nives Pećina-Šlaus

• Prof. dr. sc.
• Professor (Full) at University of Zagreb

Retinoblastoma, a rare childhood eye cancer, has hereditary and non-hereditary forms. While TNM classification helps in prognosis, understanding molecular mechanisms is vital for the clinical behavior of retinoblastoma prediction. Our study aimed to analyze the expression levels of key Wnt pathway proteins, GSK3β, LEF1, β-catenin, and DVL1, and ass...

Introduction Epigenetics play a vital role in stratifying CNS tumors and gliomas. The importance of studying Secreted frizzled-related protein 4 (SFRP4) in gliomas is to improve diffuse glioma methylation profiling. Here we examined the methylation status of SFRP4 promoter and the level of its protein expression in diffuse gliomas WHO grades 2–4....

Introduction Clinical case reports enrich medical literature by presenting rare medical issues. However, case reports that do not adhere to a standard template often lack rigor and limit their usefulness in clinical guidance. Several guidelines for reporting case reports have been structured, while further improvements are still required. The curre...

Simple Summary Gliomas are deleterious central nervous system tumors that harbor cellular heterogeneity and infiltrative capabilities. They are biologically aggressive and highly invasive tumors that lack efficient treatment. Glioma stem cells (GSCs) are a subpopulation of cancer stem cells (CSCs) with the ability for self-renewal that is responsib...

This review presents current knowledge on the molecular biology of retinoblastoma (RB). Retinoblastoma is an intraocular tumor with hereditary and sporadic forms. 8,000 new cases of this ocular malignancy of the developing retina are diagnosed each year worldwide. The major gene responsible for retinoblastoma is RB1, and it harbors a large spectrum...

In a continuous search for the improvement of antitumor therapies, the inhibition of the Wnt signaling pathway has been recognized as a promising target. The altered functioning of the Wnt signaling in human tumors points to the strategy of the inhibition of its activity that would impact the clinical outcomes and survival of patients. Because the...

Cancer remains one of the leading causes of mortality worldwide [...]

Here, we present a rarely seen example of bilateral meningiomas exhibiting different malignancy grades, I (meningothelial) and II (atypical), recorded in a 72-year-old patient. The presence of two separated lesions of different grades in a single patient can elucidate meningioma progression. To this end, the involvement of specific protein markers...

In the search for molecular candidates for targeted meningioma therapies, increasing attention has been paid to the role of signaling pathways in the development and progression of intracranial meningiomas. Although it is well known that the Wnt signaling pathway is involved in meningioma progression, the role of its central mediator, DVL1, is stil...

Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior and a lack of effective treatment methods. Despite new molecular findings, the differences between pathohistological types still require better understanding. In this in silico analysis, we investigated AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 as p...

In the present study, we investigated genetic and epigenetic changes and protein expression levels of negative regulators of Wnt signaling, DKK1, DKK3, and APC as well as glycogen synthase kinase 3 (GSK3β) and β-catenin in 64 human astrocytomas of grades II–IV. Methylation-specific PCR revealed promoter methylation of DKK1, DKK3, and GSK3β in 38%,...

Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This...

Purpose: E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal...

The acquisition of genomic instability is one of the key characteristics of the cancer cell, and microsatellite instability (MSI) is an important segment of this phenomenon. This review aims to describe the mismatch DNA repair (MMR) system whose deficiency is responsible for MSI and discuss the cellular roles of MMR genes. Malfunctioning of the MMR...

The aim of the present study was to identify TP53 exon 4 mutations in patients with meningioma and to investi‑ gate their potential association with specific tumor pathology. Nucleotide alterations were investigated in 48 meningiomas via the direct sequencing of TP53 exon 4 in patient tumor and blood samples using the DNA Sanger method with the Big...

A collection of intracranial astrocytomas of different malignancy grades was analyzed for copy number aberrations (CNA) in order to identify regions that are driving cancer pathogenesis. Astrocytomas were analyzed by Array Comparative Genomic Hybridization (aCGH) and bioinformatics utilizing a Bioconductor package, Genomic Identification of Signifi...

Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1, DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DV...

Aim To identify the involvement of Secreted Frizzled Related Protein 1 (SFRP1) promoter hypermethylation in different malignancy grades of astrocytoma and assess its association with beta-catenin, lymphoid-enhancer factor 1, and T-cell factor 1. Methods Twenty-six astrocytoma samples were collected from 2008-2015. Promoter hypermethylation was eva...

Malignancy grades of astrocytomas were analyzed for copy number aberrations by aCGH. Altogether 1438 CNA were found of which losses prevailed. We searched for regions that are more likely to drive cancer pathogenesis with Bioconductor package and Genomic Identification of Significant Targets in Cancer. On our total sample significant deletions affe...

Background: Astrocytomas are the most common primary brain tumors that are on the basis of their histology, molecular characteristics and prognosis classified into 4 different malignancy grades. As one of the key oncogenic pathways in human malignancies that has been associated to many human cancers the Wnt signaling pathway has also been implicate...

The expression patterns of critical molecular components of Wnt signaling, sFRP3 and DVL3, were investigated in glioblastoma, the most aggressive form of primary brain tumors, with the aim to offer potential biomarkers. The protein expression levels and localizations in tumor tissue were revealed by immunohistochemistry and evaluated by the semiqua...

Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by...

One of the aims of modern medicine is to fight diseases via genome editing. In order to find an even more precise and effective way to modify specific genes, scientists have developed a mechanism mediated by bacterial nucleases called the CRISPR/Cas9 system. This system was first discovered in bacteria where it is used to defend the host cell from...

Background/aim: Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma. Materials and methods: Loss of heterozygosity and mic...

Research over the last decade recognized the importance of novel molecular pathways in pathogenesis of intracranial meningiomas. In this review, we focus on human brain tumours meningiomas and the involvement of Wnt signalling pathway genes and proteins in this common brain tumour, describing their known functional effects. Meningiomas originate fr...

Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunoh...

Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades...

The development of new approaches based on wide profiling methods in studying biological and medical systems is bringing large amounts of data on a daily basis. The causes of complex diseases have been directed to the genome examination bringing formidable knowledge. We can study genome, but also proteome, exome, transcriptome, epigenome, metabolom...

Farming was established in Central Europe by the Linearbandkeramik culture (LBK), a well-investigated archaeological horizon, which emerged in the Carpathian Basin, in today's Hungary. However, the genetic background of the LBK genesis is yet unclear. Here we present 9 Y chromosomal and 84 mitochondrial DNA profiles from Mesolithic, Neolithic Starč...

A palette of copy number changes in a case of adult pilocytic astrocytoma analyzed by Array Comparative Genomic Hybridization (aCGH) is presented. Pilocytic astrocytomas are specific gliomas that are benign and biologically distinct and the molecular mechanisms responsible for their development remain unexplained. The aCGH was performed using SureP...

Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways. These multifunctional proteins, originally discovered in the fruit fly, through their different domains mediate complex signal transduction: DIX (dishevelled, axin) and PDZ (postsynaptic de...

Farming was established in Central Europe by the Linearbandkeramik culture (LBK), a well-investigated archaeological horizon, which emerged in the Carpathian Basin, in today's Hungary. However, the genetic background of the LBK genesis has not been revealed yet. Here we present 9 Y chromosomal and 84 mitochondrial DNA profiles from Mesolithic, Neol...

Background: Testicular germ cell tumours are the most common malignancies in young males. Molecular biology studies of these tumours are often contradictory. Two histological groups, seminoma and non-seminoma, differ both morphologically and in malignant behaviour. Although a common cytogenetic feature is seen, namely the amplification of the 12p...

We investigated D16S3399 marker and affirmed it as a highly polymorphic marker useful for the analysis of the human axin-1 gene. Axin-1 acts as a tumor suppressor gene and its protein is an inhibitor of the Wnt signaling pathway. We report on heterozygosity status, alleles frequency observed in a preliminary group of Croatian subjects and the optim...

The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1)...

Merlin, the protein product of NF2 gene, is one of the most versatile tumor suppressors capable of integrating different mechanisms that regulate cell proliferation, motility, survival and signaling pathways underlying and governing those mechanisms. Merlin is considered a member of the band 4.1 families of cytoskeleton-associated proteins also cal...

Frequency and mortality of renal cell carcinoma (RCC) are increasing for decades. However, the molecular background of RCC tumorigenesis is still poorly understood. In current study we investigated the expression of TCF/LEF and SFRP family members (SFRP1 and SFRP3) to gain a better understanding of biological signaling pathways responsible for epid...

Schwannomas are benign encapsulated tumors of Schwann cells, the main peripheral glia cells. The majority of schwannomas arise spontaneously and account for 8% of intracranial tumors. Those involving the cerebellopontine angle are schwannomas in 90% of cases. A case is presented of the loss of heterozygosity of the adenomatous polyposis coli (APC)...

To identify gross deletions in the NF2 gene in a panel of schwannomas from Croatian patients in order to establish their frequencies in Croatian population. Changes of the NF2 gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using two microsatellite markers, D22S444 and D22S929. The analysis with both markers demonstrated...

The numerous reports by many authors as well as our own results indicate that E-cadherin plays a role in CNS tumors – meningiomas. The suppression of E-cadherin expression is regarded as one of the main molecular events responsible for dysfunction in cell-cell adhesion. It is now apparent that downregulation of E-cadherin expression is involved in...

Epithelial-to-mesenchimal transition (EMT) is a process involved in invasion and metastasis of tumors. The occurrence of EMT during tumor progression resembles the developmental scenario and sheds light on important mechanisms for the initial step of metastasis - invasion where noninvasive tumor cells acquire motility and ultimately disseminate to...

Candidate genes involved in metastasis to the brain require investigation. In the present study, the adenomatous polyposis coli (APC) gene was analyzed in a set of human brain metastases. Gross deletions of the APC gene were tested by polymerase chain reaction/loss of heterozygosity (LOH) using the restriction fragment length polymorphism method pe...

URL: http://AtlasGeneticsOncology.org/Genes/AXIN1ID379ch16p13.html

The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metasta...

The etiology and pathogenesis of tumors of the central nervous system are still inadequately explained. In the present study the expression patterns of a critical molecular component of wnt signaling pathway - axin I was investigated in 42 patients with glioblastoma, the most aggressive form of glial tumors. Immunostaining and image analysis reveal...

Background Testicular germ cell tumors (TGCTs) are the most frequent malignances in young adult men. The two main histological forms, seminomas and nonseminomas, differ biologically and clinically. pRB protein and its immediate upstream regulator p16INK4a are involved in the RB pathway which is deregulated in most TGCTs. The objective of this study...

The association between the wnt signaling pathway and apoptosis has become more firmly established in the recent scientific literature. Many reports indicate that the wnt signaling pathway regulates apoptosis through a variety of mechanisms. The activity of wnt signaling according to specific cellular environment stimuli can either foster or restra...

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with a variable malignant potential. Two main groups of germ cell tumors occur in men: seminomas and nonseminomas. In the present study, a set of four tumor suppressor genes was investigated in testicular cancers. CDH1, APC, p53, and nm23-H1 genes were tested for lo...

Background. Testicular germ cell tumors (TGCTs) are the most frequent malignances in young adult men. The two main histological forms, seminomas and nonseminomas, differ biologically and clinically. pRB protein and its immediate upstream regulator p16INK4a are involved in the RB pathway which is deregulated in most TGCTs. The objective of this stud...

Pheochromocytomas are neuroendocrine tumors that may be either sporadic or manifestation of a familial cancer syndromes and are derived from neural-crest. In the present study oncogenes - k-ras and c-myc were investigated in sporadic human pheochromocytomas in order to identify their involvement. The aim of their investigation was to identify new m...

The molecular mechanisms and candidate genes involved in development of meningiomas still needs investigation and elucidation. In the present study 60 meningiomas were analyzed regarding changes of tumor suppressor gene E-cadherin (CDH1), a component of adherens junction and an indirect modulator of the wnt signaling. Gene instability was tested by...

Apoptosis, or programmed cell death, is a crucial mechanism for the survival of organisms and is functionally conserved in all higher eukaryotes. Molecular events in apoptosis are responsible for removal of damaged or infected cells from the cellular population, which links apoptosis to the cell cycle, replication and DNA repair. Moreover, apoptosi...

The study analyzes exon 15 of the adenomatous polyposis coli gene (APC) in a 49-year-old male patient with brain metastasis. The primary site was lung carcinoma. PCR method and direct DNA sequencing of the metastasis and autologous lymphocyte samples identified the presence of a somatic mutation. The substitution was at position 5883 G-A in the met...

In the present study changes of components of Wnt signaling pathway--axin (AXIN1) and beta-catenin (CTNNB1) in a sample of 72 neuroepithelial brain tumors were investigated. AXIN-1 gene was tested by PCR/loss of heterozygosity (LOH). Immunostaining and image analysis revealed the quantity and localization of relevant proteins. Polymorphic marker fo...

Insulinomas and phaeochromocytomas are neuroendocrine tumours that may be either sporadic or manifestation of a familial cancer syndromes and are both derived from the neural crest. In the present study, gene components of different signalling pathways were investigated in sporadic human insulinomas and phaeochromocytomas to identify the responsibl...

The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study 33 meningiomas were analyzed regarding genetic changes of tumor suppressor gene Adenomatous polyposis coli (APC), a component of the wnt signaling. Gene instability was tested by polymerase chain reactio...

Rapid advancements in the field of genomics, enabled by the achievements of the Human Genome Project and the complete decoding of the human genome, have opened an unimaginable set of opportunities for scientists to further unveil delicate mechanisms underlying the functional homeostasis of biological systems. The trend of applying whole-genome anal...

From 1996 to the present, the remains of 61 individuals killed during the 1991 War in Croatia were recovered from both dried out and functioning wells. Positive identification was established in 60.7% or 37/61 cases. Remains recovered from the same geographical region but from non-well settings were identified in 77.4% or 1256/1623 cases. The purpo...

We investigated the expression of E-cadherin and beta-catenin in melanoma. Both proteins are components of adherens junctions but also play signalling roles in the wnt signal transduction pathway. Seventy malignant melanomas were analysed by immunohistochemistry and evaluated by image analysis as staining density, i.e. light permeability (LP). Comp...

The genetic basis as well as mechanisms of development of germ cell tumors of the CNS are still unexplained. In the present article changes of Ecadherin (CDH1) and beta-catenin (CTNNB1) genes in two CNS germ cell tumors are reported. Both gene products are components of adherens junctions, but are also involved in the Wnt signaling pathway. A case...

This paper focuses on changes in E-cadherin (CDH1), adenomatous polyposis coli (APC), and beta-catenin (CTNNB1) in 50 tumors of the central nervous system. All gene products are components of adherens junctions, but are also involved in wnt signaling. The results of our analysis showed LOH of CDH1 gene in 31% of meningiomas examined (significant co...

tumor lesion in the right parietal region, with the surrounding zone of perifocal oedema. During the operative procedure the tumor was maximally reduced using a microneurosurgical technique. The collected tumor tissue was frozen in liquid nitrogen and transported to the laboratory, where it was immediately frozen at )75 � C. The peripheral blood sa...

Beta-catenin is bound to E-cadherin in adherens junction formation, but also functions as a signaling molecule in the WNT pathway. We investigated beta-catenin expression in 41 superficial spreading melanomas. Our melanoma sample was analyzed by immunohistochemistry and evaluated by image analysis as staining density, i.e. light permeability (LP)....

Adenomatous polyposis coli, (APC) and E-cadherin (CDH1) tumor suppressor genes were investigated in human pheochromocytoma. Both genes are components of adherens junctions, but are also involved in wnt signalling in which one of the target molecules is c-myc protein. Fifteen sporadic pheochromocytomas were tested for gene instability by PCR/loss of...

This review seeks to bring novel findings of genetic basis of melanoma. CDKN2A and CDK4 genes residing on chromosomes 9p21 and 12q14, as well as MC1R gene located at 16q24 are main candidates responsible for melanoma development and progression. These genes together with signal transduction pathways in which they are implied are primarily changed i...

The molecular mechanisms involved in the development and progression of laryngeal cancer, specifically squamous cell carcinoma, still need further investigation and elucidation. Twenty-two laryngeal squamous cell carcinomas were analyzed in our study regarding genetic changes of two tumor suppressor genes: Adenomatous polyposis coli (APC) and E-cad...