Genes and cancer

Summary: In the article a short description is given of genes involved in the development of neoplasia including tumour suppressors and oncogenes as well as the minimal number of changes required to transform a normal cell into a neoplastic one. Changes detected in mitochondrial DNA in solid tumours are also mentioned. 
 

Key Words: cancer, oncogenes, suppressor genes, cell cycle

Apoptosis and tumors

Summary: General characteristics of apoptosis and mechanisms leading to activation of caspases and endonucleases, the main executors of apoptosis is described. The crucial role in these processes of mitochondria and the proteins released from them � procaspase 9, cytochrom c and AIF factor is also shown. Information is also presented about membrane receptors, their ligands as well as various regulatory proteins, those from BCL-2/BAX and IAPs families included. It is pointed out that changes in the level of expression and/or properties of regulatory proteins characterize various tumor cells. The apoptotic pathway induced and regulated by suppressor (p53, pRb) and oncogenic (c-MYC) proteins was also depicted. 

Key Words: apoptosis, membrane receptors, ligands, mitochondria, caspases, endonucleases, BCL-2/BAX, p53, pRb, c-MYC

Cancer and aging

Summary: In aging population growing up rapidly causes of cancers are observed. Lost of immunological answer caused by DNA double-strand breakes, longer exposition to carcinogens, decreasing activity of DNA-repair system in aging cells, defects of supressor genes are caused carcinogenesis. DNA-defects of aging and cancer cells by hipermethylation GpC island of gene promoters are observed. Changes in extracellular matrix of aging and transformed cells are responsible forcell migration causing metastasis.

Słowa kluczowe: cancer, aging, senescence, DNA-methylation, extracellular matrix.
 

Lipids of cancer cell -- selected topics

Summary: Lipid metabolism plays a pivotal role in membrane biogenesis, synthesis of lipid second messengers and membrane repair processes. Recently, disturbances in a balance between synthesis and degradation of lipids have been ascribed to participate at early stages of cancer development. Therefore, in this article the following topics are discussed: relationship between membrane damage and cancerogenesis, characteristics of changes of membrane structure and lipid metabolism in cancer cells, a role of polyunsaturated fatty acids and lipid microdomains in multidrug resistance, and interactions of some anti-cancer drugs with membrane lipids. Taken together, these observations suggest that at early stages of cancer development crucial changes in lipid metabolism occur, that lead to remodelling of membrane chemical composition, disturbances of signal transduction, and changes of electric and structural properties of cell membranes.

Key Words: cancerogenesis, membrane structure, oxidative stress, phospholipid metabolism, polyunsaturated fatty acids, lipid microdomains, multidrug resistance

Genetic diagnostics of cancer

Summary: The article shows possibilities of improvement of cancer diagnosis based on general biological features of cancer. A short description of commonly used methods and their advantages and disadvantages are discussed. Diagnostic methods based on detection of changes in genetic material (mutations and translocations) as well as clonal growth of cancer cells are described in greater detail. Techniques of detection of cancer cells in the context of healthy cells/tissues are presented. The article also discusses other uses of the tumor's molecular properties in prognosis and choice of therapy in particular.

Key Words: molecular diagnostics, tumor markers, prognosis
 

Immunological mechanisms in cancer. Cancer immunotherapy in animal models and in the clinic

Summary: Cancer immunotherapy is not a standard in clinical treatment of tumors, while first attempts were made several years ago. The appearance of tumor specific antigens (TSA) e.g. Bcr/abl, or tumor associated antigens (TAA) in cancer cells may be used theoreticaly in cancer therapy. Tumor cells in transformation process accumulate products of oncogenes and/or loss the functional products of tumor suppressor genes. This processes change intracellular signaling roads regulating cell proliferation and/or apoptosis of cancer cells and effect the tumor growth progression. Tumor progression is, however, not only due to genetic transformation of cancer cells but as well to changes in response to the tumor of immunological system of the organism. The immunological tolerance of the organism develop in cancer, the situation when cancer cells and cytotoxic T cells (CTLs) coexist. The attack of CTL against tumor cells is blocked. Predendritic cells (pDC) are present in tissues, and they endocytose virally infected or pre-cancer cells. Then the pDC translocate to peripheral lymphatic tissue e.g. lymph nodes where they mature to dendritic cells (DC) and cross-present the antigens of infected cells or cancer cells to naive T cells CD8+ and CD4+. The antigens of apoptotic cells may be cross-presented by DC to T lymphocytes as well, and probably chaperone proteins (hsp) are involved in this process. The above observations were used to stop the immunological tolerance in cancer as part of immunotherapy. The scheduled procedure is, first surgical removal of the tumor. The tumor tissue is divided on portions and banked in liquid nitrogen. Then, about one months after surgery, the tumor tissue is recovered from the bank, tumor cells are isolated and ex vivo irradiated or treated with Mafosfamide (Maf) with a dose sufficient to block cell divisions, but not to kill the cells. The cell suspension is than injected s.c. to the patient four times in one week intervals. The activation of immunological system should induce removal of cancer cells remaining after surgery. The clinical results in colon cancer immunotherapy are similar as in chemotherapy after surgery. It is important, that immunotherapy does not expose the patient to bacterial, viral or fungal infections and does not induces secondary cancers as compared to chemotherapy.

Key Words: dendritic cells, TSA, TAA, cancer immunotherapy
 

Localization of maternal determinants in the oocytes of vertebrates

Summary: In many vertebrates and invertebrates the development of the embryo depends on the proper, often asymmetrical, localization of maternal determinants throughout the egg cytoplasm (ooplasm). One of the best known examples of such asymmetrical localization is the localization of maternal RNAs in Xenopus oocytes. Here, different RNAs localized to the vegetal cortex of the oocyte participate in germ cell determination and in axial patterning of the embryo. There are two different pathways of RNA localization during Xenopus oogenesis. Such mRNAs as Xcat2, Xwnt11, Xdazl, Xpat, Xotx1 and Xlsirts utilize the Early (METRO, message transport organizer) pathway. All these RNAs are localized in the mitochondrial cloud and are transported within its fragments to the vegetal cortex of the oocyte. After fertilization the fragments of mitochondrial cloud containing localized RNAs become a part of the germ plasm. It is believed that the components of germ plasm are responsible for the specification of germ cell fate in developing embryo. Such mRNAs as Vg1 and VgT utilize the Late (Vg1-like) pathway. This pathway does not involve mitochondrial cloud and it is microtubule and endoplasmic reticulum dependent. The Late pathway localizing RNAs play a role in endoderm and mesoderm specification and axial patterning during the development of the Xenopus embryo. 

Key Words: oogenesis, embryogenesis, RNA localization
 
 

Cellular differentiation in early development of the mouse  

Summary: During the preimplantation period of mammalian development two morphogenetic events take place: compaction and cavitation. In consequence, mammalian blastocyst is composed of two cell lineages: trophectoderm and inner cell mass. These cell lineages differ in morphology as well as in their developmental fate. This review summarizes the current knowledge of the cellular and molecular mechanisms, that participate in early differentiation events during mammalian development.

Key Words: embryo, cleavage, blastocyst, compaction, cavitation, trophectoderm, inner cell mass

GIBCO BRL reagents for eukaryotic transfections

Summary: A wide variety of techniques are used to deliver macromolecules (DNA, RNA, proteins) into eukaryotic cells. This process is transfection. This method allows examining gene expression, protein synthesis as well as malignant transformation. No single method works best, that's why GIBCO BRL (Life Technologies) presents eukaryotic transfection reagent family.

Key Words: transfection, Lipofectamine, Cellfectin, cationic lipid reagents, eukaryotic cell
 

Regulation of myogenesis

Summary: --- 

Key Words: ---
 

Differentiation of the thymic epithelial cells

Summary: Thymic epithelial cells constitute the major component of the thymus microenvironment responsible for maturation of immunocompetent T-cells. Differentiation of epithelial cells requires a series of stage- and site-specific cellular interactions. In the early stages of histogenesis of the thymus the interactions between pharyngeal endoderm and mesenchymal cells of neural crest take place. They are controlled by the activity of several genes and its products, transcription factors. Suppression of these genes results in various developmental changes in thymus. Next stage in the differentiation of epithelial cells is initiated by the process of colonisation of epithelial primordium of the thymus by lymphoid cells. The interactions between lymphoid and epithelial cells via several adhesion molecules and growth factors induce the process of differentiation and cause phenotypic changes both in thymocytes and epithelial cells. These interactions lead to the appearance of epithelial cell subpopulations and control microarchitecture of the thymus.

Key Words: epithelial cells, thymus, embryonic development, differentiation, cellular interactions