Trastuzumab in the adjuvant treatment of breast cancer.

Four large randomized trials to assess efficacy and toxicity of trastuzumab in adjuvant systemic therapy of breast cancer have been initiated. Results clearly demonstrate, that adjuvant treatment of trastuzumab significantly improves outcomes for women with HER2 positive breast cancer. The clinically most significant adverse events of trastuzumab are serious-infusion related reactions and cardiotoxicity. Benefit for patient should be considered according to advantage versus risk (Tab. 1, Fig. 2, Ref. 17) Full Text (Free, PDF) www.bmj.sk.

Genetic tests for predicting the toxicity and efficacy of anticancer chemotherapy.

The standard anticancer therapy based "on one size fits all" modality has been determined to be ineffective or to be the cause of adverse drug reactions in many oncologic patients. Most pharmacogenetic and pharmacogenomic studies so far have been focused on toxicity of anticancer drugs such as 6-mercaptopurine, thioguanine, irinotecan, methotrexate, 5-fluorouracil (5-FU). Variation in genes are known to influence not only toxicity, but also efficacy of chemotherapeutics such as platinum analogues, 5-FU and irinotecan. The majority of current pharmacogenetic studies focus on single enzyme deficiencies as predictors of drug effects; however effects of most anticancer drugs are determined by the interplay of several gene products. These effects are polygenic in nature. This review briefly describes genetic variations that may impact efficacy and toxicity of drugs used in cancer chemotherapy.

Endothelaemia--a marker of vascular damage.

OBJECTIVES: The aim of the study was to determine the amount of circulating endothelial cells (CECs) in patients with an advanced cardiovascular (CV) disease, compare the values with a control group and finally to ascertain if there are statistically significant differences within the studied patient groups. BACKGROUND: Endothelaemia has been intensively studied as a marker of vascular injury. Clinical studies have demonstrated an increased endothelaemia in patients at high CV risk but also in certain non-cardiovascular disorders. Its possible usage in the diagnostics of the acute coronary syndrome and for CV risk assessment needs further investigations. METHODS: Thirty six hospitalized patients were studied. Quantitative measurement of endothelaemia was performed by the method developed by J. Hladovec. It is based on ECs counting in Bürker's chamber after their isolation with platelets and the removal of the latter by an addition of adenosine-diphosphate. RESULTS: The mean baseline endothelaemia was significantly higher in patients with increased cardiovascular risk when compared with the control group (1.38 +/- 0.899): ACS (4.9 +/- 1.59, p < 0.05) and PAOD (3.74 +/- 0.61, p < 0.05). When comparing the mean endothelaemia values in patients with PAOD before (2.67 +/- 0.86) and after (3.88 +/- 0.77) surgery, a significant increase of endothelaemia was observed (p < 0.05). CONCLUSION: Our pilot study, though limited by a relatively small number of patients, proved a significant increase of endothelaemia in patients at high CV risk, which is consistent with other available data. The introduction of newer specific methods based on immunomagnetic principles may provide a wider use of endothelaemia measurement in clinical settings (Fig. 3, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Red wine polyphenols prevent endothelial damage induced by CCl4 administration.

It became evident in the present study that carbon tetrachloride (CCl(4)), in addition to its known liver and renal toxicity, causes serious damage to endothelial cells. The preventive effect of red wine on cardiovascular diseases has been documented in a number of human population studies as well as in animal experimental models. In this study, the endothelium protective effect of polyphenolic compounds isolated from red wine was studied in rats administered 0.5 ml of CC(4)/kg body weight intraperitoneally twice a week for 8 weeks. Endothelemia (endothelial cells/10 microl of plasma) was used as the marker of endothelial cell injury in vivo. Chronic CCl(4) treatment for 8 weeks lead to a 3-fold increase of free endothelial cells circulating in the blood when compared to the baseline values (2.5+/-0.3). Parallel oral administration of polyphenols 40 mg/kg/day significantly decreased the endothelemia. Polyphenolic compounds alone did not produce significant changes. Three weeks of spontaneous recovery after the 8-week treatment with CCl(4) did not lead to a marked decrease of endothelemia, but the administration of red wine polyphenols during the 3-week period significantly decreased free endothelial cells in the blood. It can be concluded that long-term administration of CCl(4) may serve as a useful experimental model of endothelial damage. The red wine polyphenolic compounds exert a powerful protective effect on endothelial cells from the injury caused by CCl(4). This effect was documented by decreased endothelemia that corresponded to diminished endothelial cell swelling and detachment evaluated by histology of the vascular intima. The endothelium protective effect may be one of the key factors that contribute to the preventive action of red wine on cardiovascular diseases.