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MiRNAs are small, non-coding molecules of ribonucleic acids of approximately 22 bp length, which serve as regulators of gene expression and protein translation due to interference with messenger RNA (mRNA). MiRNAs, which take part in the regulation of cell cycle and apoptosis, may be associated with carcinogenesis. Aberrant expression of miRNAs in endometrial cancer might contribute to the endometrial cancer initiation or progression, as well as metastasis formation, and may influence cancer invasiveness. Specific-miRNAs expressed in endometrial cancer tissues may serve as diagnostic markers of the disease, prognostic biomarkers, or play an important part in oncological therapy We aimed to describe the role of miRNAs in endometrial cancer with special consideration of miRNA 205.

Numerous studies have revealed that MDM2 oncoprotein is upregulated in different types of cancer. Additionally, it was demonstrated that in some cases, MDM2 may inhibit the neoplastic transformation process. In other words, MDM2 protein can be considered as an oncogene or as a tumor suppressor depending on the appropriate cellular context. MDM2 functions on different levels in the cell, which is a consequence of its complex structure, a plethora of interacting partners and regulation through numerous postranslational modifications. Thus, an alteration of the delicate balance in MDM2 activity can influence transformation and cancer development. Genomic instability is a hallmark of cancer, which inversely correlates to the activity of DNA damage response. In the case of not transformed cells MDM2 inhibits double strand brakes (DSBs) repair, hence stimulating carcinogenesis. In cancer cells MDM2 stimulates cytostatic-induced DSBs repair, thus leading to chemoresistance.

MicroRNAs (miRNAs) are a group of small molecules, about twenty nucleotides in length. They are involved in the regulation of gene expression mainly at a posttranscriptional level. This function depends on their complementarity to the 3'UTR regions of mRNAs. MicroRNAs are essential for proper development and functioning of the organism. They are so important because of their participation in such processes as angiogenesis, apoptosis, cell cycle control and oncogenesis. Over thirty percent of human genes are controlled by miRNAs. This indicates the great importance of these molecules. Alterations of numerous cellular processes can be caused by the dysregulation of miRNA expression. Such disturbances are observed in cancer cells, and signatures of microRNA expression are specific to particular types of cancer. It is suggested that miRNAs may serve as diagnostic and prognostic factors in oncologic and hematooncologic disorders. The expression of specific miRNAs can indicate benign or aggressive course of disease. The overall survival or time to treatment are also possible to estimate based on the microRNA expression profile. Knowledge about changes in miRNA expression observed in leukemia patients may enable the selection of appropriate individual therapy. Recent reports indicate that various hematooncologic disorders may be well characterized by microRNAs circulating in plasma or serum. It is of great potential importance, considering the availability of material for analysis, simplicity of diagnostic procedures and shortening of time required to conduct them.

Continuous improvement of appropriate methods of dealing with cancer require active search for the possibility of applying more and newer targeted therapies. Scientific reports, in addition to best-described proteins KRAS, PI3K emphasize the important role in carcinogenesis. This paper presents overview PIK3CA mutations in the path PI3K/PTEN/Akt the most common cancers. Targeted to stop the most important components of this path can be used to create targeted therapies. PIK3CA mutation may also be a predictive factor in the selection of targeted therapies. A lot of questions remain unanswered such as: how the structure and biochemical effects of intracellular affect different mutations in PIK3CA, and all mutations in the gene lead to the activation of p110a subunit? Additional research on the biochemical structure and cell structure are necessary to complete the discovery of PIK3CA gene function and, in particular subunits of p110a.

Epigenetic changes, including DNA methylation, influence the structure of chromatin, gene expression and genomic stability. It appears that the abnormal pattern of DNA methylation may be important in pathological conditions, including colorectal cancer. The most common pathway leading to this tumor is adenoma-carcinoma sequence. It was reported that during this process changes in the pattern of DNA methylation occurred, but the question whether these changes are the causes of neoplastic transformation of colorectal cancer or the consequences of pathological changes in the cancer cells is still open. Thus, changes in DNA methylation pattern may influence the pathogenesis of colorectal cancer but this hypothesis has not been confirmed experimentally and there is a need for research determining the relationship between changes in DNA methylation profile and colorectal cancer. By analyzing methylation of DNA sequences a molecular subgroup of this tumor has been distinguished. It is characterized by a high frequency of methylation of genes and it was denoted CpG islands methylator phenotype (CIMP). Changes in the pattern of DNA methylation are used as molecular markers for diagnosis and screening of colorectal cancer. A better understanding of changes in DNA methylation in colorectal cancer may help to facilitate prognosis and prediction of the disease and to improve its diagnosis.

Posttranslational modifications of histones belong to epigenetic mechanisms involved in normal development and maintaining the pattern of gene expression. Histone modifications can influence the global and local organization of chromatin structure. The effects of histone modifications can have mutual synergistic or antagonistic influence regulating access of chromatin-binding proteins and in this way determining the transition between transcriptionally active and inactive chromatin. Deregulation of this mechanism may be associated with many pathological conditions, including cancer. The question whether histone modifications belong to the reasons or the consequences of neoplastic transformation remaines unanswered. Based on research on restoring silenced gene expression through administration of histone deacetylase inhibitor or by knockout of the gene encoding the histone methyltransferase in cancer, it seems that at least some modifications of histones may have a causal nature. Histone modifications may be reversible which is a rationale to generate a new set of anticancer drugs--inhibitors of enzymes that modify histones.

Splicing of pre-mRNA is one of the post-transcriptional modifications in which introns are removed from primary transcript and exons are joined. pre-mRNA splicing reactions are catalyzed by dynamic complex called spliceosome. Exons can be joined on different manners in a process known as alternative splicing, that provide production of multiple mRNA and protein isoforms from relatively low number of genes. Alternative splicing is regulated by cis elements localized within exons or introns and trans-acting factors including spliceosome components and members of the SR and hnRNP protein family that exert antagonistic effects on splicing. Aberrant pre-mRNA splicing may be caused by mutations in cis elements and altered expression of splicing factors. This review describes disturbances in splicing of genes controlling proliferation and metastasis that can lead to tumoral transformation. Also, potential applications of abnormally spliced transcripts that may potentially serve as diagnostic biomarkers of cancer or targets in anticancer therapy are discussed.

DNA methylation plays an important role in the regulation of gene expression. Tumor cells are characterized by alterations of DNA methylation pattern, namely local CpG island hypermethylation and genome wide hypomethylation. The hypomethylation of the genome affects many repetitive sequences and transposable elements and is believed to results in chromosomal instability and increased mutations events. In this review we summarize the current knowledge concerning epigenetic mechanisms related to cancer, especially the relationship of DNA hypomethylation to carcinogenesis.

DNA adducts, one of genetic damages markers, precede and finally can lead to oncogenic mutations. They appear in genome as a result of DNA bases damages caused by various and numerous environmental factors eg. ultraviolet light, ionic radiation, toxins and also endogenic substances, for example estrogens. It is believed that the creation of DNA adducts is a necessary but insufficient process for the neoplastic transformation of the cell. The following review presents concise knowledge about the DNA adducts creation and their sequels served in healthy and cancerous tissues of the female genital organs, on the base of the available data.

Peroxisome proliferators-activated receptors are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. The PPAR subfamily consists of three members: PPAR-alpha, PPAR-sigma (NUC-1 or beta) and PPAR-gamma. PPARs regulate gene expression by binding, as heterodimers with retinoid X receptors (RXR), to specific response elements (PPREs) in the promoter regions of target genes. The prostaglandin 12 especially, all arachidonic acid metabolites and polyunsaturated fatty acids are naturally occuring PPAR ligands. Synthetic PPAR ligands are thiazolidinediones (TZDs--rosiglitazone, pioglitazone, troglitazone). Activation of nuclear hormone receptors has been identified as an approach to induce differentiation and inhibit proliferation of cancer lines. The anti-proliferative, pro-differentiation effects of PPAR activators (TZDs) suggest that these compounds might be useful in slowing the proliferation of un-differentiated tumour cells. TZDs inhibit proliferation of human breast, prostate and colon cancers, both in vitro and in tumours derived from these cells implanted into rodents. Furthermore, recent studies show that PPAR-gamma ligands are potent inhibitors of angiogenesis, a process essential for solid-tumour growth and metastasis. In conclusion, the evidence to date suggests that activation of PPAR should suppress tumour growth and development. This represents an exciting novel therapeutic application of TZDs. In present paper, structural features of PPARs, their gene transcription mechanisms and recent developments in the discovery of their biological functions are reviewed.

Microarrays are one of the latest breakthroughs in experimental molecular biology, which allow monitoring of gene expression for tens of thousands of genes in parallel and are already producing huge amounts of valuable data. Microarray RNA expression on a genome-wide range is now a proven technology, although the idea of analysis of expression many genes in one sample is not new. Since the development of clone printing technology and oligonucleotide synthesis allowed to produce high density microarray. In this publication we provide the information about the technology, available detection systems and data analysis software. Comprehensive review of current or fundamental papers using microarray technology application in immunology, rheumatoid arthritis, oncology, cystis fibrosis research, primary pulmonary hypertension, psychiatry, and allergic airways inflammation is also included.

The aim of the study of 41 multiform glioblastomas was the analysis of p53-protein immunoreactivity in neoplastic cells and evaluation of relationship of this biologic marker to tumour proliferation activity. Positive p53 expression was observed in 24 (58.5%) tumours, the negative one in 17 tumours (41.5%). Proliferation indexes of PCNA, anti-Ki6 and AgNORs showed high values in the multiform glioblastoma p53 positive group, but without statistical differences in comparison with the group of p53-negative glioblastomas. Significant differences were observed in survival time of patients with p53 positive tumours in comparison with p53-negative ones. In 15 patients with p53-positive multiform glioblastomas survival time was less than 6 months (62.5%) on the contrary with only 4 patients with similar survival time in p53-negative glioblastoma group (23.5%). Our results suggest that p53 expression in multiform glioblastoma cells, generally considered as the indirect index of p53 suppressor gene, reflects aggressive stadium of neoplastic disease and significantly worsens the prognosis.

This paper summarizes the current knowledge on the role of genetic factors in the development of thyroid neoplasms. The introduction of the methods and concepts of molecular genetics (as, e.g. recombinant DNA technology) have elucidated etiopathogenesis of the majority of thyroid tumours and, in the future, can make the diagnosis easier. Mutations of genes involved in the control of cellular growth and/or differentiation (ras, c-myc, RET, met) affect the development of thyroid neoplasms. Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has been reported in thyroid follicular carcinomas. Activation of tyrosine kinase, whether by specific oncogene amplification or by rearrangement, appears to be highly specific for the transformation of thyroid follicular cells into papillary tumours. Cytogenetic studies have shown frequent clonal abnormalities in thyroid follicular adenomas and carcinomas.

This article describes the significance of the mouse transgenic model in elucidation of the role and the oncogenic potential of such genes as N-ras, pim-1, bcl-2, myc and p53. The role of gene targetting by homologous recombination in the study of preneoplastic state in the mice model was also discussed.

Main aim of this study was evaluation of application of stable clones of transforming cells, containing DNA of plasmid vector for the investigation of oncogenes. Plasmid vector was constructed basing on pSV2neo vector, containing activated oncogene c-Ha-ras-1, derived from pT 24-C3 which was followed by evaluation of phenotypic and genetic changes in standard line of NIH3T3 mouse fibroblast line after transfection with constructed plasmid. After two weeks of culture in selective conditions, transformants resistant to geneticin were obtained and analysis of clones was performed after transfection with constructed vector containing ras oncogene and after transfection pSV2neo. Analysis of efficiency of cloning and transformation basing on growth independent from placement and morphology and investigation of karyotypes demonstrated similar irregularities in both investigated groups and subchromosomal aberrations of NIH3T3 cells were even more frequent than in initial lines of NIH3T3 cells. Southern hybridization with pSV2neo-ras probe demonstrated that only restrictive DNA fragments, obtained by Pst1 enzyme contain copies of neo in cell genomes. Integration of gene cf geneticin-resistance increases thus normally unstable genetically NIH3T3 cells.

This review describes the role of cellular protooncogenes in cancer development. The chemical activation of cellular protooncogenes is also presented.

Oxygen, a necessary element for the life of a cell is also the source of active state of oxygen including free radicals, which can induced damage to cellular DNA. The damage can result in deleterious biological consequences such as the initiation and promotion of cancer. In this paper the characterization of the DNA damage and molecular mechanisms causing this damage is presented.

The role of glycosphingolipids in the expression of neoplastic phenotype. III. Alterations in glycosphingolipids of tumor cells related to their metastatic potential and tumorigenicity. This review describes changes in glycosphingolipids related to metastatic and tumorigenic properties of malignant cells. The possible effects of such alterations on malignant behavior of cells is discussed.