MEG3: a novel long noncoding potentially tumour-suppressing RNA in meningiomas.

Meningiomas represent one of the most common types of primary intracranial tumours. However, the specific molecular mechanisms underlying their pathogenesis remain uncertain. Loss of chromosomes 22q, 1p, and 14q have been implicated in most meningiomas.

Preparation, preliminary screening of new types of steroid conjugates and their activities on steroid receptors.

There were synthesized new types of ribbon type steroidal dimers derived from three types of steroidal skeletons (cholic acid, etienic acid, estrone) using Cu(I) catalyzed 1, 3-dipolar cycloaddition reaction. Steroid parts of the molecular "ribbons" are linked by heterocyclic moiety, namely by 2,6-bis((1H-1,2,3-triazol-1-yl)-methyl)pyridine. Compounds synthesized possess different cytotoxic and hormone receptor modulating activities.

The MS(E)-proteomic analysis of gliadins and glutenins in wheat grain identifies and quantifies proteins associated with celiac disease and baker's asthma.

Precise content of gliadin (Glia) and glutenin (Glu) proteins in wheat grain are largely unknown despite their association with celiac disease, various allergies, and physical processing properties of wheat. Developing methods to quantitatively measure clinically relevant proteins could support advancement in understanding exposure thresholds and clinical study design. The aim of this study was to use a data-independent mass spectrometry (MS(E)) approach for quantifying gliadin and glutenin proteins in wheat grain.

Evaluation of laparoscopic resection of colorectal carcinoma from the viewpoint of molecular biology.

Aim: Detection of the possible impact of surgical management on the occurrence of minimal residual disease (MRD) in patients with colorectal carcinoma (CRC) in bone marrow samples, portal and peripheral blood samples. Comparison of MRD prevalence in patients with laparoscopic resection of CRC and those with open colorectal resection. Assessment of the potential impact of MRD on the relapse of the disease and overall survival of patients.

Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy.

Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDI-TOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs.

Combination of prednisolone and low dosed dexamethasone exhibits greater in vitro antileukemic activity than equiactive dose of prednisolone and overcomes prednisolone drug resistance in acute childhood lymphoblastic leukemia.

Introduction: Glucocorticoids, particularly prednisone/ prednisolone and dexamethasone, play a prominent role in the treatment of pediatric patients with acute lymphoblastic leukemia due to their ability to induce apoptosis in susceptible cells. Current therapeutic protocols use prednisone for both the prophase and the induction phase of the therapy because the greater antileukemic activity of dexamethasone is compromised by its high frequency of serious adverse reactions.

Aim: To compare, for the first time, the in vitro antileukemic activity of prednisolone alone to that of a combination of prednisolone and dexamethasone using dexamethasone at a very low and presumably safe dosage (1/50 w/w).

Occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic cancer.

Aims: The aim of this study was to test the hypothesis that occult tumour cells in peritoneal lavage are a negative prognostic factor in pancreatic adenocarcinoma.

Methods: Real-time RT-PCR analysis of CEA, EGFR and hTERT transcript levels was used to identify occult tumour cells in peritoneal lavage samples from 96 pancreatic cancer patients.

Results: We found significant association between CEA expression levels in peritoneal lavage and clinical stage.

Soybeans grown in the Chernobyl area produce fertile seeds that have increased heavy metal resistance and modified carbon metabolism.

Plants grow and reproduce in the radioactive Chernobyl area, however there has been no comprehensive characterization of these activities. Herein we report that life in this radioactive environment has led to alteration of the developing soybean seed proteome in a specific way that resulted in the production of fertile seeds with low levels of oil and β-conglycinin seed storage proteins. Soybean seeds were harvested at four, five, and six weeks after flowering, and at maturity from plants grown in either non-radioactive or radioactive plots in the Chernobyl area.

Seeds in Chernobyl: the database on proteome response on radioactive environment.

Two serious nuclear accidents during the last quarter century (Chernobyl, 1986 and Fukushima, 2011) contaminated large agricultural areas with radioactivity. The database "Seeds in Chernobyl" (http://www.chernobylproteomics.

Hepatoprotective effect of MMP-19 deficiency in a mouse model of chronic liver fibrosis.

Liver fibrosis is characterized by the deposition and increased turnover of extracellular matrix. This process is controlled by matrix metalloproteinases (MMPs), whose expression and activity dynamically change during injury progression. MMP-19, one of the most widely expressed MMPs, is highly expressed in liver; however, its contribution to liver pathology is unknown.

A comparison of Direct sequencing, Pyrosequencing, High resolution melting analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations in non small cell lung carcinomas.

Background: It is mandatory to confirm the absence of mutations in the KRAS gene before treating metastatic colorectal cancers with epidermal growth factor receptor inhibitors, and similar regulations are being considered for non-small cell lung carcinomas (NSCLC) and other tumor types. Routine diagnosis of KRAS mutations in NSCLC is challenging because of compromised quantity and quality of biological material. Although there are several methods available for detecting mutations in KRAS, there is little comparative data regarding their analytical performance, economic merits, and workflow parameters.

Synthesis and cytotoxicity of some D-mannose click conjugates with aminobenzoic acid derivatives.

Two sets of new conjugates obtained from d-mannose derivatives and o-, m-, and p-substituted benzoic acid esters interconnected through a triazole ring were synthesized by Cu(I) catalyzed azide-alkyne cycloaddition. All synthesized compounds were tested for their in vitro cytotoxic activity against seven cancer cell lines with/without multidrug resistance phenotype as well as non-tumor MRC-5 and BJ fibroblasts. Butyl ester of 4-aminobenzoic acid 6c showed the highest activity among all tested compounds, however, it was active only against K562 myeloid leukemia cells.

[Biomarkers in the detection of minimal systemic dissemination in lung cancer patients].

Introduction: Minimal systemic disease (MSD) means the presence of circulating or disseminated tumour cells in mesenchymal compartments of a patientts' body (lymphatic nodes, blood or bone marrow). The aim of our pilot study was to identify sensitive and specific markers for MSD detection in 50 lung cancer patients, who underwent curative surgery in the I. Department of Surgery, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital Olomouc in 2009 and 2010.

Akt expression and compartmentalization in prediction of clinical outcome in HER2-positive metastatic breast cancer patients treated with trastuzumab.

Trastuzumab is effective in about half of HER2-positive breast cancer patients. The PI3K/Akt signalling pathway plays an important role in the process of primary and secondary resistance to anti-HER2 targeted therapy. We evaluated the relationship between expression, activation and subcellular localization of selected Akt isoforms and response to trastuzumab-based anti-HER2 targeted therapy in patients with HER2-positive metastatic breast cancer.

Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas.

Unlabelled: Epidermal growth factor receptor (EGFR) is an important therapeutic target and a poor prognosis factor in head and neck squamous cell carcinoma (HNSCC). The aim of the study was to analyze EGFR expression and KRAS and EGFR mutational status and to correlate it with treatment response to anti-EGFR therapy combined with radiotherapy in 29 patients with advanced head and neck squamous cell carcinomas (HNSCC).EGFR gene expression normalized to GAPDH and EGFR variant type III (EGFRvIII) was detected in tumor tissue using real time reverse transcription -PCR.

Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid.

The aim of this work was to synthesize a set of heterocyclic derivatives of lupane, lup-20(29)-ene, and 18α-oleanane, and to investigate their cytotoxic activities. Some of those heterocycles were previously known in the oleanane (allobetulin) group; however, to our knowledge the syntheses and biological activities of lupane heterocycles have not been reported before. Starting from betulin (1) and betulinic acid (2), we prepared 3-oxo compounds and 2-bromo-3-oxo compounds 3-10, 2-hydroxymethylene-3-oxo compounds 11-13 and β-oxo esters 14-16.

High lapatinib plasma levels in breast cancer patients: risk or benefit?

Aims And Background: Lapatinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptors 1 (EGFR/HER1) and 2 (HER2) used in the treatment of patients with HER2-positive breast cancer. The aim of the present study was to determine lapatinib plasma levels in breast cancer patients treated with lapatinib plus capecitabine.

Patients And Methods: We assessed lapatinib plasma levels in blood samples from 21 breast cancer patients treated with lapatinib plus capecitabine using the standard regimen in an expanded access program.

Aurora kinase inhibitors: progress towards the clinic.

The Aurora kinases (serine/threonine kinases) were discovered in 1995 during studies of mutant alleles associated with abnormal spindle pole formation in Drosophila melanogaster. They soon became the focus of much attention because of their importance in human biology and association with cancer. Aurora kinases are essential for cell division and are primarily active during mitosis.

Mass spectrometry-based analysis of proteomic changes in the root tips of flooded soybean seedlings.

Flooding injury is a major problem in soybean cultivation. A proteomics approach was used to clarify the occurrence of changes in protein expression level and phosphorylation in soybeans under flooding stress. Two-day-old seedlings were flooded for 1 day, proteins were extracted from root tips of the seedlings and digested with trypsin, and their expression levels and phosphorylation states were compared to those of untreated controls using mass spectrometry-based proteomics techniques.

MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients.

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM.

Synthesis of various 5-alkoxymethyluracil analogues and structure-cytotoxic activity relationship study.

A number of 5-alkoxymethyluracil analogues were synthesized to evaluate their cytotoxic activity. 5-Alkoxymethyluracil derivatives 1 were prepared via known nucleophilic substitution of 5-chloromethyluracil 5 and subsequently transformed to their corresponding nucleosides 2. All prepared compounds were submitted to cytotoxic activity testing against drug sensitive and drug resistant leukaemia cells and solid tumour derived cell lines.

Mutations in EGFR signal pathway in correlation with response to treatment of head and neck cancers.

Unlabelled: The prognostic and predictive value of the epidermal growth factor receptor (EGFR) expression and some genetic alterations in an EGFR signal pathway, such as the EGFR amplification, the EGFR activating tyrosine kinase domain mutations or the k-ras gene mutation were investigated in our study. The aim of the research was to evaluate the occurrence of the above-mentioned biomarkers in correlation with a therapeutic response and survival in patients with locoregionally advanced spinocellular head and neck cancers.

Keywords: Head and neck cancer, EGFR, predictive marker, k-ras, EGFR amplification, EGFR tyrosine kinase domain mutation.

Synthesis and significant cytostatic activity of 7-hetaryl-7-deazaadenosines.

A series of 7-aryl- and 7-hetaryl-7-deazaadenosines was prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes, or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro antiproliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells.

Proteomic comparison of virulent phase I and avirulent phase II of Coxiella burnetii, the causative agent of Q fever.

Coxiella burnetii, a category B biological warfare agent, causes multiple outbreaks of the zoonotic disease Q fever world-wide, each year. The virulent phase I and avirulent phase II variants of the Nine Mile RSA 493 and 439 strains of C. burnetii were propagated in embryonated hen eggs and then purified by centrifugation through Renografin gradients.