Neoadjuvant concomitant chemoradiotherapy has become a standard treatment of locally advanced rectal adenocarcinomas (LARA). It leads to shrinkage of the tumor mass and subsequently to an increase in complete resections (R0 resections), increasing a feasibility of sphincter-sparing intervention avoiding colostomy. It is based on concurrent application of fluoropyrimidines (5-fluorouracil, capecitabine) and radiotherapy (45 - 50,4 Gy). It shows less acute toxicity and improves local control rate in comparison to adjuvant treatment. Unfortunately, neoadjuvant chemoradiotherapy is not beneficial for all patients. The treatment response ranges from a complete pathological remission (pCR, ypT0ypN0) to a resistance. It is reported that cca 15 percent of patients with advanced rectal cancer show pCR which is indicative of improved long-term prognosis. DESIGN: The following is a review of the significance of neoadjuvant concomitant chemoradiotherapy in the treatment algorithm of patients with LARA and summary of potentional clinical-pathological and molecular markers of response prediction to neoadjuvant therapy. The most important clinical studies concern serum tumor markers levels, clinical lymph node classification. The components of the carcinogenic pathways are explored, including oncogenes, tumor supressor genes, microsatellite instability (MSI) and potentional markers involved in apoptosis, angiogionesis, proliferation as well as metastasis and invasion, are reviewed. Finally, the role of specific enzymes associated with the metabolism of fluoropyrimidines are examined. CONCLUSIONS: No one marker has been consistently identified as clinically applicable. Studies designed to determine the potentional markers are hampered by various techniques as well as tumor heterogenity and recent scientific approach--studying individual molecular markers. Gene expression profiling analysis of multiple genes from the same tumor is becoming reality. We suppose that this assessment will lead in future in finding combination of markers for predicting prognosis and response to therapy in rectal cancer., Garajová Ingrid, Svoboda M., Slabý O., Kocáková L., Fabian P., Kocák I., Vyzula R., and Lit.: 71
Srdcovo-cievne ochorenia patria medzi vážne príčiny úmrtia ľudí. Ateroskleróza a oxidačne modifi kované lipoproteíny výraznou mierou prispievajú k patológii týchto ochorení. Významnú úlohu v antiaterogénnych procesoch hrajú HDL- -lipoproteíny a s nimi asociované enzýmy, najmä paraoxonáza. Živočíšne paraoxonázy (PON1, PON2 a PON3) sú rodinou významných hydroláz závislých od Ca2+ a aktívnych voči celému radu rôznych substrátov. Aj keď skutočný fyziologický substrát pre jednotlivé PON sa nepozná, v súčasnosti sa považujú za významné substráty laktóny, niektoré oxidované fosfolipidy, produkty oxidácie kyseliny arachidónovej a dokozahexaénovej ako aj laktóny odvodené od N-acetyl-homoserínu. Všetky PON sa pokladajú za enzýmy s významnou antiaterogénnou aktivitou. Ich aktivity sa stanovujú voči rôznym substrátom, pričom arylesterázová aktivita PON1 sa považuje za smerodatnejší ukazovateľ antiaterogénnej aktivity ako paraoxonázová aktivita PON1. Laktonázová aktivita je pravdepodobne bližšie k fyziologickému substrátu ako paraoxon, či fenylacetát., Cardiovascular diseases (CV) are one of the most important mortal diseases. Atherosclerosis and oxidatively modifi - ed lipoproteins are main risk factors that contribute to the pathology of CV diseases. HDL as well as HDL-associated enzyme paraoxonase play an important role in the antiatherogenic processes. Mammalian paraoxonases (PON1, PON2 and PON3) are a unique family of calcium dependent hydrolases, with enzymatic activity towards a broad range of substrates. Although PONs physiological substrates have not been identifi ed yet, some studies suggest some lactones, or some specifi c oxidized phospholipids, or products of oxidation of arachidonic and docosahexaenoic acid as well as N-acyl-homoserine lactones to be suitable substrates for the enzyme. All three members of the PON family were shown to protect from atherosclerosis development. Their biological activities are determined towards different substrates and arylesterase activity is more decisive indicator of antiatherogenic activity than paraoxonase activity. However structure- -reactivity studies indicate that lactonase activity of PON1 is its native activity., Ďuračková Z., Andrezálová L., and Lit.: 28
Súčasné odporúčania Národného cholesterolového edukačného programu pre liečbu dospelých jedincov s dyslipidémiami nemajú vekové limity, ale zdôrazňujú potrebu dôkladného fyzikálneho hodnoteni a stavu pacienta nad 65 rokov, pred zahájením hypolipemickej liečby. Mnoho štúdií, ktoré boli použité, nezahrňovalo staršie ženy, špeciálne ženy nad 80 rokov. Taktiež štúdie zahrňujúce seniorov potvrdili vysoké kardiovaskulárne riziko u probandov s vysokými, či nízkymi koncentráciami cholesterolu. Tento jav je označovaný ako strata schopnosti celkového cholesterolu "predvídať" kardiovaskulárne príhody. Hlavno u príčinou tohto javu, ktorý sťažuje identifikáciu vysokorizikových pacientov v staršej populácii je tzv. syndróm stareckej krehkosti. Na druhej strane, nízke koncentrácie HDL cholesterolu zostávajú najsilnejším prediktorom kardiovaskulárneho rizika a nestrácajú na svojej prediktívnej sile s postupom veku. Triacylglyceroly sú asociované s kardiovaskulárnym rizikom v populácii stredného veku. V štúdii, ktorej sa zúčastnili iba pacienti nad 65 rokov, boli koncentrácie triaclyglycerolov prediktívnym faktorom len u starších žien, nie u mužov., The current guidelines of the National Cholesterol Education Programme for treatment of adults with hyperlipidemia do not have age limits but specify that thorough physical examination is necessary before lipid lowering therapy is initi ated in patients over 65 years of age. Many studies used to formulate these guidelines did not include older women, especially those older than 80 years. Numerous studies involving older participants reported high cardiovascular disease risk for subjects with high as well as with low cholesterol concentrations. This was interpreted as a loss of ability of total cholesterol to predict cardiovascular events. The main ca use of this phenomenon contributing to difficulties in identifying subjects at higher cardiovascular risk in older population is the frailty syndrome. On the other hand, low HDL cholesterol concentrations remain the most powerful predictor of cardiovascular risk and it does not loose any of its predictive power even with advancing age. Triglycerides are associated with cardiovascular risk in middle age cohorts. A study including participants over 65 years of age only showed triglycerides to be a powerful independent predictor of cardiovascular disease in women but not in men., Viola Vargová, Marek Pytliak, Viola Mechírová, and Lit.: 29