Quantitative profiling of genes associated with cancer pathways in brain tumors.

Background: Brain tumors are a heterogeneous group of malignancies characterized by inter- and intratumoral heterogeneity. Among them, the most aggressive and, despite advances in medicine, still incurable remains glioblastoma. One of the reasons is the high recurrence rate of the disease and resistance to temozolomide, a golden standard in chemotherapy of brain tumors.

Immunodetection of Pyruvate Carboxylase Expression in Human Astrocytomas, Glioblastomas, Oligodendrogliomas, and Meningiomas.

Pyruvate carboxylase (PC) is an enzyme catalyzing the carboxylation of pyruvate to oxaloacetate. The enzymatic generation of oxaloacetate, an intermediate of the Krebs cycle, could provide the cancer cells with the additional anaplerotic capacity and promote their anabolic metabolism. Recent studies revealed that several types of cancer cells express PC.

Different Approaches for the Profiling of Cancer Pathway-Related Genes in Glioblastoma Cells.

Deregulation of signalling pathways that regulate cell growth, survival, metabolism, and migration can frequently lead to the progression of cancer. Brain tumours are a large group of malignancies characterised by inter- and intratumoral heterogeneity, with glioblastoma (GBM) being the most aggressive and fatal. The present study aimed to characterise the expression of cancer pathway-related genes ( = 84) in glial tumour cell lines (A172, SW1088, and T98G).

The effect of temozolomide on apoptosis-related gene expression changes in glioblastoma cells.

Background: Glioblastoma (GB) is the most common and biologically the most aggressive primary brain tumor of the central nervous system (CNS) in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy, and chemotherapy with temozolomide (TMZ). Despite numbers of studies, a resistance to chemotherapy is the major obstacle to successful GB treatment.

Expression of 3-Methylcrotonyl-CoA Carboxylase in Brain Tumors and Capability to Catabolize Leucine by Human Neural Cancer Cells.

Leucine is an essential, ketogenic amino acid with proteinogenic, metabolic, and signaling roles. It is readily imported from the bloodstream into the brain parenchyma. Therefore, it could serve as a putative substrate that is complementing glucose for sustaining the metabolic needs of brain tumor cells.

Associations between matrix metalloproteinase, tissue inhibitor of metalloproteinase and collagen expression levels in the adjacent rectal tissue of colorectal carcinoma patients.

As the commonest type of cancer in Europe and the third most common type of cancer worldwide, colorectal carcinoma (CRC) poses a challenge for numerous scientific studies. At present, the cause of this disease is remains to be elucidated, but early diagnosis is only one solution to prevent serious health complications. As a structural scaffold, the extracellular matrix (ECM) is in direct contact with tumour cells and significantly interferes with tumour progression.

γ- and δ-Tocotrienols interfere with senescence leading to decreased viability of cells.

Senescence is an irreversible permanent cell cycle arrest accompanied by changes in cell morphology and physiology. Bioactive compounds including tocotrienols (vitamin E) can affect important biological functions. The aim of this study was to investigate how γ- and δ-tocotrienols can affect stress-induced premature senescence.

Noninvasive study of brain tumours metabolism using phosphorus-31 magnetic resonance spectroscopy.

Phosphorus-31 magnetic resonance spectroscopy (31P MRS) is currently not accepted as a diagnostic tool in the neuro-oncological practice, although it provides useful non-invasive information about biochemical processes ongoing in the intracranial tumours. This pilot study was aimed to present the diagnostic capability of the 31P MRS in brain tumour examination, even its application on clinical 1.5T MR scanner.

Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects - a preliminary study.

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non-specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy.

Cobalt chloride affects the death of SH-SY5Y cells induced by inhibition of ubiquitin proteasome system. Role of heat shock protein 70 and caspase 3.

The aim our study was to investigate protective effect of cobalt chloride (CoCl2) in the model of proteasome stress of neuroblastoma SH-SY5Y cells induced by bortezomib, an inhibitor of 26S proteasome. We have focused our interests on Hsp70 and activation of caspase 3. Finally, we have compared the effect of CoCl2 with an effect of the pre-treatment of the cells with 17-AAG, an inhibitor of Hsp90 that is capable to induce expression of Hsp70, or with IOX2, an inhibitor of isoform 2 of prolyl hydroxylase that increases stability of hypoxia inducible factor 1α (HIF1α).

Methylation status of KLF4 and HS3ST2 genes as predictors of endometrial cancer and hyperplastic endometrial lesions.

Endometrial carcinoma is one of the most common tumours in developed countries. In addition to the active role of genetic factors, epigenetic changes also have an important effect. The present study analysed the methylation status of kruppel like factor 4 (KLF4) and heparan sulfate‑glucosamine 3‑sulfotransferase 2 (HS3ST2) genes in three endometrial tissue types for carcinoma prediction.

miRNA in a multiomic context for diagnosis, treatment monitoring and personalized management of metastatic breast cancer.

Metastatic breast cancer is characterized by aggressive spreading to distant organs. Despite huge multilevel research, there are still several important challenges that have to be clarified in the management of this disease. Therefore, recent investigations have implemented a modern, multiomic approach with the aim of identifying specific biomarkers for not only early detection but also to predict treatment responses and metastatic spread.

The metabolism of 5-methylcytosine residues in DNA.

The fundamental biochemical processes of 5-methylcytosine (5-mC) synthesis, maintenance, conversion and removal determine the time and spatial pattern of DNA methylation. This has a strong effect on a plethora of physiological aspects of cellular metabolism. While the presence of 5-mC within the promoter region can silence gene expression, its derivative - 5-hydroxymethylcytosine exerts an opposite effect.

Differential mRNA expression of the main apoptotic proteins in normal and malignant cells and its relation to in vitro resistance.

Background: Apoptosis plays an important role in the development and homeostasis of multicellular organisms and its deregulation may result in many serious diseases, including cancer. Now it is clear that some oncogenic mutations disrupt apoptosis, leading to tumour initiation, progression or metastasis. Here, expression of apoptotic genes in context of drug resistance was investigated.

Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737.

Colorectal carcinoma (CRC) that represents one of the major causes for cancer-related death in humans is often associated with over-expression of anti-apoptotic proteins of Bcl-2 family. The aim of presented study was to determine the effect of ABT-737 inhibitor of anti-apoptotic proteins Bcl-2, Bcl-XL and Bcl-w as well as cyclin-dependent kinase 2 (CDK2) inhibitor SU9516 alone and in combination with ABT-737 on survival of colorectal cell lines HT29 and Caco-2. We have shown that both Caco-2 and HT29 cells that are relatively resistant to ABT-737 are also partially sensitive to SU9516, which increased sensitivity of Caco-2 but not HT29 cells to ABT-737.

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients.

DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients.

Role of S-adenosylmethionine cycle in carcinogenesis.

Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases.

The role of CYP17A1 in prostate cancer development: structure, function, mechanism of action, genetic variations and its inhibition.

Androgens play an important role during the development of both normal prostate epithelium and prostate cancer and variants of genes involved in androgen metabolism may be related to an increased risk of prostate disease. Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) is a key regulatory enzyme in the steroidogenic pathway; it catalyses both 17α-hydroxylase and 17,20-lyase activities and is essential for the production of both androgens and glucocorticoids. In this review, we focus on the structure and enzymatic activity of CYP17A1 and the mechanism of modulation of CYP17A1 activities.

Proteasome Stress Triggers Death of SH-SY5Y and T98G Cells via Different Cellular Mechanisms.

Overload or dysfunction of ubiquitin-proteasome system (UPS) is implicated in mechanisms of neurodegeneration associated with neurodegenerative diseases, e.g. Parkinson and Alzheimer disease, and ischemia-reperfusion injury.

Microfluidic profiling of apoptosis-related genes after treatment with BH3-mimetic agents in astrocyte and glioblastoma cell lines.

Glioblastoma (GB) is the most frequent and biologically the most aggressive primary brain tumor in adults. Standard treatment for newly diagnosed GB consists of surgical resection, radiotherapy and chemotherapy. Resistance to therapy is a major obstacle, even with optimal treatment with a survival median of only 12-15 months.

DNA Methylation Machinery in the Endometrium and Endometrial Cancer.

During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis.

Bcl-2 family proteins: master regulators of cell survival.

The most prominent function of proteins of the Bcl-2 family is regulation of the initiation of intrinsic (mitochondrial) pathways of apoptosis. However, recent research has revealed that in addition to regulation of mitochondrial apoptosis, proteins of the Bcl-2 family play important roles in regulating other cellular pathways with a strong impact on cell survival like autophagy, endoplasmic reticulum (ER) stress response, intracellular calcium dynamics, cell cycle progression, mitochondrial dynamics and energy metabolism. This review summarizes the recent knowledge about functions of Bcl-2 family proteins that are related to cell survival.

The Role of Heat Shock Proteins in Leukemia.

Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are molecular chaperones; their expression is increased after exposure of cells to conditions of environmental stress, including heat shock, heavy metals, oxidative stress, or pathologic conditions, such as ischemia, infection, and inflammation. Their protective function is to help the cell cope with lethal conditions. The HSPs are a class of proteins which, in normal cells, are responsible for maintaining homeostasis, interacting with diverse protein substrates to assist in their folding, and preventing the appearance of folding intermediates that lead to misfolded or damaged molecules.

New molecular aspects of endometrial carcinoma.

Endometrial cancer is the most commonly diagnosed gynecological cancer and its incidence is increasing worldwide. The number of patients with this disease is likely to continue to grow, including younger patients. It is a complex disease driven by abnormal genetic and epigenetic alterations, as well as environmental factors.