The Use of Cytogenetic Analysis in B-cell Lymphoma Diagnosis

Summary: Many studies in malignant lymphoma have discussed correlation between histologic subtypes and specciifc cytogenetic abnormalities. Several cytogenetic abnormalities in lymphoma cells are associated with characteristic morphology, specific immunophenotype an have distinctive clinical features. Certain chromosomal markers detected by conventional G-banding and fluorescent in situ hybrydization (FISH) methods. Typical cytogenetic changes of Non Hodgkin's Lymphoma (NHL), eg. the translocation t(8;14)(q24;q32) in Burkitt's lymphomas (BL), t(14;18)(q32;q11) in follicular lymphomas (FL) or t(11;14)(q13;q32) in Mantle cell lymphomas (MCL) may by useful in definition of NHL subtypes and, may require different treatment strategies. Currently, the practical application occur karyotypic changes, not only for diagnostic purposes but also for predictic response to therapy and prognosis.

Key words: lymphoma, karyotypic aberration, translocation.

CD39 (NTPDase 1) – Characteristics of the Enzyme And its Role in Regulating Coagulation and Inflammation Processes

Summary: CD39 (NTPDase 1), an ectoenzyme expressed on vascular endothelium and blood cells, plays a significant role in regulation of blood clotting, inflammation and angiogenesis. CD39 hydrolyses extracellular ATP and ADP, and therefore modulates function of P2 receptors, for which these nucleotides are agonists. Nucleoside tri- and diphosphates elicit in cells various responses such as proliferation, differentiation, chemotaxis and cytokine release. Loss of CD39 activity associated with activation of endothelial cells and ischemia-reperfusion process leads to activation and aggregation of platelets. Crucial role of CD39 in angiogenesis is indicated by significant impairment of new blood vessel formation in vivo and in vitro in cd39 knockout mice. In this review, CD39 is characterized and current data related to posttranslational modifications of the molecule, CD39 like family and potential therapeutical applications of CD39 are presented.

Key words: ADP, ATP, ATPDase, CD39, endothelial cell, NTPDase 1, platelet, thrombosis.
 

The Dynamic of The Steroid Hormone Receptors Distribution in the Ovary

Summary: In the adult ovary the process of follicle development, which involves cell proliferation and differentiation, take place. The expression of genes in the ovary occurs in a sequential hormone-dependent manner and is dependent on numerous factors. Some of the proteins are known to be expressed at defined stages of follicular development and luteinization. As ovarian functions are also regulated by ovarian steroids, the distribution of their receptors is crucial. Immunohistochemistry, hybridization in situ and biochemical analysis provide data which, when they are analysed jointly, may led to a better understanding of folliculogenesis.

Key words: steroids, receptors, immunohistochemistry, in situ hybridization

Sucrose Metabolism in Plants and its Regulation under Environmental Stresses

Summary:This paper discusses the mechanism that regulate sucrose metabolism and source-sink relations and describes possible functions for sucrose-cleaving enzymes. The influence of abiotic stress factors such as low temperature, nutrient deficit, drought, salinity, anaerobiosis and environmental pollution on sucrose metabolism are also explored.

Key words: carbohydrate allocation, sucrose metabolism, stressing factors

Regulation of Expression and Function of Nur77 Family of Nuclear Receptors and Their Role in the Control Points of Signaling Pathways Leading to Apoptosis, Differentiation and Synthesis of Steroid Hormones

Summary: The orphan nuclear receptors Nur77, Nurr1 and Nor-1 are the members of Nur77 family and of the steroid/thyroid hormone receptor superfamily. These proteins are mediators in signaling pathways leading to apoptosis of thymocytes, neuronal differentiation, synthesis of steroid hormones. Therapeutic intervention in these processes should be preceded by the knowledge of mechanisms of regulation of expression and function of Nur77 family proteins and their role in different signaling pathways. Expression and function of Nur77 is regulated on the levels of transcription of gene and fosforylation of protein. Nur77 family proteins function as transcription activators in the form of monomers, homodimers and heterodimers with retinoid X receptors. Nur77 family proteins are involved in cross-talk of signaling pathways dependent on receptors of growth factors, hormones, antigens (T cell receptor) with glucocorticoids and retinoids dependent signaling pathways. In the signaling pathway leading to apoptosis Nur77 is exported from the nucleus to the mitochondria and may act as an adaptor protein.:

Key words: Nur77, Nurr1, orphan nuclear receptors, signaling pathways, apoptosis
 

Gene Expression Profiling of Tumor Cells

Summary: For biologists studing cancer, a major chalange is to identify the underlying molecular changes that switch cells to tumorigenic and metastatic state. Previous research has focused on the contribution of individual genes to tumour formation and metastasis. Now, creation of human tumour cells with defined genetic elements as well as gene-expression profiling using DNA microarrays, is revolutionizing our approach to study cancer.

Key words: tumour, metastasis, telomerase, retinoblastoma, p53, RhoC, fibronectin, thymosin ?4.
 

Methods for Representing Water in Molecular Dynamics Simulation Studies

Summary: Water plays a crucial role in living cells; therefore, proper treatment of water in molecular dynamics (MD) simulations of biological systems is very important. A brief review of most popular methods for representing water in MD simulations is presented. The methods range from simple modifications of Coulombic term in  the potential function through solvatation potential and polarization of solvent, to explicite inclusion of solvent molecules. Possible applications and validity of the methods is discussed. Various models of a water molecule whose parametrization reflects properties of water in the condensed phase are presented.

Keywords: molecular dynamics (MD) simulations, water

Regulatory Elements Agr and Sar in Staphylococcus Aureus

Summary: Staphylococcus aureus is a human pathogen, capable of causing a wide range of diseases, including life-threatening. The expression of virulence factors is controlled mainly by two global regulatory systems called agr and sar. The agr locus is composed of two transcripts: RNA III (effector molecule) and RNA II. The last encodes four proteins involved in stimulation of transcription of RNA II and RNA III. The locus sar is composed of three overlapping open reading frames, all encoding DNA-binding protein SarA, an agr activator. The result of interactions between agr and sar is reduction of expression of surface proteins and increasing secretion of exoproteins. The agr operon is a part of cell-to-cell communication mechanism called „quorum sensing”, based on self generated signal molecules (autoinducers). Owing to the usage of autoinducers bacteria can collectively regulate the expression of wide spectrum of virulence factors dependently on population density. Quorum sensing seems to be an attractive new target for the development of novel antibiotics-blocking the intercellular signalling mechanism will help to fight drug-resistant bacteria. Regulatory elements homologous to described above were discovered in coagulase-negative staphylococci and additional sar-homologous genes in S. aureus.

Key words: agr, sar, virulence factors, quorum sensing, S. aureus

Breast Cancer: Alterations of Methylation and Expression Genes of Nuclear Receptors: ? Estrogen (ER?) and ?2 Retinoic Acid (RAR?2)

Summary: Epigenetic alterations of genes coding proteins which contribute to regulation of cell proliferation and differentiation, are a significant element of early development of breast cancer. Two nuclear proteins (i.e. estrogen receptor ?, ER?, and retinoic acid receptor ?2, RAR?2) play an important role in the regulation of cells function. Clinical and genetic studies of breast cancer cells resistant to antiestrogen and retinoid therapy, reveal that cell resistance results from the lack of ER? and RAR?2 genes expression on transcriptional level. The trans-criptional silence of genes, including also ER? and RAR?2, is frequently associated with hypermethylation of promoter regions of these genes. Alterations of promoter methylation are the most significant element of a complex process which leads to chromatin inactivation. Estimation of methylation pattern changes of ER? and RAR?2 genes, and possibilities of gene reactivation should be important for the selection of effective therapy to inhibit development and invasion of breast cancer cells.

Key words: DNA methylation, breast cancer, estrogen receptor ?, retinoic acid receptor ?2.

[Postepy Biologii Komorki 2002; 29: 121–139]

The Role of Molecular Cytogenetics in B-Cll Cells Clonal Proliferation Analyses

Summary: Clonal chromosomal abnormalities are present in leukemic cells of almost half of studied patients with chronic lymphocytic leukemia. B-CLL lymphocytes are characterized by low mitotic indexs in vitro despite mitogen stimulation, which makes conventional cytogenetics difficult. That is why the molecular techniques like FISH to interphase nuclei are often employed in cytogenetic analyses. The most frequent structural abnormalities in B-CLL involve  the partial deletion of chromosome 13 in subcentromeric region 13q14, partial deletion of chromosome 11 in 11q23 region, trisomy 12, and mono or biallelic loss of tumor supprresor gene TP53 in chromosome 17p13. The significance of above markers to clonal proliferation of B-lymphocytes and/or to B-CLL progression was assessed.

Key words: chronic lymphocytic leukemia-B lymphocytes, clone cytogenetics

Cell Cycle Checkpoints: Do We Know Their Molecular Background?

Summary: Nobel prize laureates in physiology and medicine in 2001 were three researches – Leland Hartwell, Paul Nurse and Timothy Hunt, honoured for their pioneering studies on molecular mechanisms regulating cell cycle progression. They discovered that cell cycle is  controlled through cooperation of some serine-threonine kinases and specific proteins – cyclins. These kinases, later named cyclin-dependent kinases, appeared to be indispensable for progression of cells through every phase of the cell cycle. The classic nowadays concepts of START and cell cycle checkpoints, introduced by Hartwell, point on importance in the regulation of cell proliferation of intra- and extracellular signals integration and on precize monitoring of cell readiness to pass to the next phase of cell cycle, after succesful completion of the previous one. In the article the information is given about main proteins and processes in which they participate in various cell cycle checkpoints, activated by DNA damage (in phases G1/S, S and G2) or perturbations in the mitotic spindle formation (during mitosis).

Key words: cell cycle, cell cycle checkpoints, cyclin-dependent kinases, ATM kinase, Cdc25 phosphatase, suppressor protein p53