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Part of breast and ovarian cancer cases develops on the hereditary predisposition, i.e. mutation in one of predisposing genes. Although this proportion is relatively small, 5-10% of all breast and ovarian carcinomas, it represents a group with clearly defined etiologic factor. Predictive analysis of unaffected family members allows to identify individuals at high risk of cancer and to include them into the programme of primary and secondary cancer prevention. Following article presents basic review of the hereditary predisposition to breast and ovarian cancer focusing especially on BRCA1 and BRCA2 genes, which are responsible for almost three-quarters of those hereditary tumours.

Objective: The article presents a review of basic information on incidence and detection of BRCA 1 and BRCA 2 genes mutations. Results of investigation in a group of women with ovarian and breast cancer are presented., Design: Retrospective clinical-laboratory study and review., Setting: Department of Gynaecology and Obstetrics, 1st Medical Faculty of Charles University, Prague, Apolinárská 18, Czech Republic., Material and Methods: Investigated group consisted of 16 persons--12 patients with ovarian or breast cancer and 4 healthy relatives of a woman--breast cancer patient and a carrier of BRCA 1 gene mutation. Protein truncation test (PTT) was performed in order to detect BRCA 1 gene mutation. This test detects mutations leading to premature termination of protein synthesis. Truncated proteins are easily discriminated from full size., Results: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history., Conclusions: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies. Genetic testing and counselling including investigation of some other genetic and environmental factors, related to cancer risk, may be of clinical significance in patients with increased risk of certain malignancies.

The incidence of breast cancer continuously increases in developed countries. The introduction of screening methods such as mammography or ultrasound lead to higher proportion of early diagnosed tumors. However, even in early stage tumors occult neoplastic cells can spread to the organism. Such tumor cells are very likely precursors of distant metastases. Using several monoclonal antibodies against epithelial mucins or cytokeratins on the cell surface could be detected one tumor cell among 10(5) or 10(6) of normal bone marrow cells. These cells are not detectable by routine histopathologic exam. More sensitive but also more costly and technically demanding are PCR assays. The sensitivity might reach almost 1:10(7). Prospective clinical trials using immunocytochemistry have shown that the presence of stained cells in bone marrow is clearly associated with shorter disease free survival and overall survival. In the near future we may use the bone marrow examination for the presence of occult tumor cells in order to improve current staging system or as a surrogate marker in the decision-making in regard to adjuvant systemic therapy or in the assessment of efficacy of adjuvant treatment. The review summarizes contemporary knowledge assembled in preclinical and clinical studies.

This review focuses on apoptosis and its regulation as a tool of principal control mechanism of tissue homeostasis. Defects in regulation of apoptosis contribute to a various pathological processes, including tumor development, chronic inflammatory diseases, immunological disorders and many others. Apoptosis influences sensitivity to radiotherapy and chemotherapy of tumours. Microscopically the apoptosis is characterized by morphological changes, which result in the formation of apoptotic bodies. Apoptosis is an active process, which require synthesis and activation of a set of the specific cellular proteins. Among them, the key role belongs to the family of cystein proteases--caspases activated either through the death receptors or via activation steps starting with the release of a mitochondrial cytochrome c. Activation of caspases promotes the activation of downstream effectors leading to the cleavage of target cellular proteins and genomic DNA. The members of Bcl-2 family and p53 are- the others important proteins influencing the regulation of apoptosis. Enhancing of our knowledge about apoptosis and its mechanisms highly improves the rationale for diagnostics and therapy in oncology.

The authors submitted a very brief review of some biological properties of iron in particular protein-bound iron and on the immense amount of iron which surrounds us (it is the fourth most frequent element). In the human organism there is no physiological system for iron elimination. Therefore its absorption is regulated and restricted. Some substances promote its absorption, other inhibit it. An important factor in the regulation of iron absorption are the iron reserves of the organism, the amount of dietary iron and the enhanced erythropoiesis (incl. the ineffective one), while reduced erythropoiesis does not affect iron absorption. Ascorbic acid forms chelates with iron and thus remains soluble and can be absorbed despite the alkaline pH in the duodenum. Unbound trivalent iron remains insoluble. An important asset to rational iron therapy are Lauberger's discovery of ferritin (1936), assessment of the iron plasma level (Heilmeyer and Plötner, 1937), Laurell's discovery of transferrin (1947), and Addison's RIA method for assessment of the serum ferritin level (1974). Sideropenia remains the most widespread deficiency in human pathology, sideropenic anaemia the most readily diagnosed anaemia which is, however, most wrongly treated.

Following up of specific melanogenesis metabolite excretion in the course of malignant melanoma disease is useful for the disease prognosis assessment. The authors elaborated a modified synthesis technique of 6-hydroxy-5-methoxy and 5-hydroxy-6-methoxyindole, eumelanin pigment precursors. The elaborated synthesis is economically and temporally reasonable and the synthesized compounds accord, as proved by means of elementary analysis, thin layer (TLC) and high performance liquid chromatography (HPLC) and last but not least by nuclear magnetic resonance (NMR), with demands for reference compounds needed for isomer hydroxymethoxyindole quantification in urine.