[Molecular biological diagnostics of KRAS and BRAF mutations in patients with colorectal cancer - laboratory experience]. / Molekulárne biologická diagnostika mutací genu KRAS a BRAF u pacientu s kolorektálním karcinomem - zkusenosti laboratorního pracoviste

BACKGROUND: Targeted biological therapy based on blocking growth factor receptors and inhibition of cancer-inducing signaling pathways is a new treatment facility for patients with colorectal cancer (CRC). Therapeutic agents are monoclonal antibodies targeting epidermal growth factor receptor (EGFR). Gene aberrations in the EGFR-induced pathways are negative predictors of therapeutic response. Determination of -non-mutated KRAS is a requirement for the indication of targeted anti-EGFR therapy in the present time, BRAF mutation analysis is recommended. Comparison of our results with published data and verification of routine laboratory methods in relation to diagnostic kits were the purposes of this study. PATIENTS AND METHODS: In addition to routine methods based on PCR, direct sequencing as well as two diagnostic kits for KRAS (codon 12 and 13) and BRAF (codon 600) mutation analysis were used for 132 patients. RESULTS: KRAS mutations were detected in 45 patients (34%), V600E mutation of the BRAF gene in 9 patients (7%). Both mutations simultaneously were not detected. Tissues from primary tumor and metastases were available from 33 patients. KRAS mutation was detected in 13 cases of this group. KRAS mutations in tumor and metastasis were of the same type in 9 patients; types of mutation in both tissues were different in one case. KRAS mutation only in one tissue was detected in 3 cases. BRAF mutation in both tissues was detected in the 4 patients. A low percentage of tumor cells in 17 patients specimen did not allow performance of routine analysis and diagnostic kit was used. CONCLUSION: The frequency of KRAS and BRAF mutations in our cohort of patients corresponds to published data. The suitability of metastatic tissue analysis due to tumor heterogeneity was confirmed. KRAS analysis requires a comprehensive methodological approach with regard to reduced DNA quality and different percentage of tumor cells in tissue. For this reason, commercial diagnostic kits constitute a suitable supplement to standard methods.

[Semisynthetic cellulose derivatives as the base of hydrophilic gel systems]. / Polosyntetické deriváty celulosy jako základ hydrofilních gelových systému.

The field of drug technology widely ulilizes gel systems of high-molecular substances, which have a number of advantages, such as low toxicity, availability, unique physical properties, biocompatibility, mucoadhesivity, and others. Gel systems are used in the field of local as well as general therapy, in both shape-specific and shape-non-specific dosage forms, in medicaments of the first, second, and third generations. An important group of gels employed in pharmacy are hydrophilic gels or hydrogels, most frequently composed of hydrophilic polymers of natural, semisynthetic and synthetic origin. Though cellulose derivatives as the representatives of polymers of semisynthetic origin are used in pharmaceutical technology for a long time, their research continues and their other possible uses are being searched for. Their advantages include especially safety, easy availability, and a relatively low price. The review paper describes selected cellulose derivatives, their properties and uses in pharmaceutical technology with regard to their use in the field of production of gel systems.

[Hemostatic effects of oxidized cellulose]. / Hemostatické úcinky oxidované celulosy.

Oxidized cellulose ranks among nontoxic and biocompatible biopolymers. Oxidized regenerated cellulose (ORC) is manufactured from regenerated cellulose derived from wood pulp containing about 50% of cellulose. To obtain purified cellulose, it is necessary to decompose it in a chemical way and subsequently put it together to make "regenerated" cellulose. Thanks to its good hemostatic effects, high biosolubility and biodegradability, antioxidant and wound-healing properties, oxidized cellulose represents a suitable means for the therapy of bleeding conditions in various fields of medicine. In addition, the confirmed bactericidal effects of oxidized cellulose towards a wide spectrum of aerobic and anaerobic pathogens increase the therapeutic potential of this agent for use in clinical practice. At present there is a renewed interest in its wider use in clinical practice and in an improvement of the knowledge of its mechanisms of effects, which are tested in vitro, on animal models as well as in clinical studies. The present paper attempts to summarize the hitherto knowledge of hemostatic properties of oxidized cellulose and also to characterize other possible biological effects.

[A cellulose derivative with a potential to become an active pharmaceutical substance as well as an auxiliary substance]. / Oxycelulosa--celulosový derivát s potenciálem ucinné i pomocné látky.

The review article is focused on one of the wide range of pharmaceutically and medicinally employed cellulose derivates--oxycellulose. This substance, prepared by oxidation of cellulose, in contrast to cellulose esters and ethers, has not been not employed in practice in a wide extent yet. However, recent studies reveal its potential use in modern therapeutical systems, whether as a release-modifying excipient, a drug carrier, or also an active substance with ability of hemostasis, prevention of tissue adhesion after surgical operations, and a substance with antimicrobial and immunomodulating activity, whose unique property of biodegradability, promoted by hypoallergenicity and non-irritability, has not been observed in any of the hitherto used cellulose derivates. The article presents a comprehensive overview about the history of this derivate, from its physico-chemical properties through the description of the ability of biodegradability to its already realized and planned utilization.