With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine. Increased urinary or serum concentrations of neopterin have been associated with poor prognosis across a spectrum of malignant disorders of different primary location. Neopterin concentration in peripheral blood as well as in the tumor microenvironment correlates with phenotypic and functional changes of lymphocytes, indicating immune dysfunction. Increased neopterin concentrations are also accompanied by increased rate of conversion of tryptophan to kynurenine. Increasing neopterin concentrations also accompany side effects of anticancer treatment and could predict subsequent complications. Although almost four decades have elapsed since the discovery of increased neopterin concentrations in cancer patients, the full potential of neopterin as a biomarker in this setting has not been so far realized.

• Klíčová slova
• Kynurenine, neopterin, tryptophan,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The aim of the present study was to examine the changes in intima-media thickness (IMT) and myocardial perfusion in association with other laboratory risk factors for atherosclerosis in patients treated with therapy that targeted vascular endothelial growth factor (VEGF). IMT, myocardial perfusion and laboratory risk factors of atherosclerosis were studied in 58 patients with metastatic colorectal carcinoma or metastatic renal cell carcinoma prior to and at 3-monthly intervals during anti-VEGF treatment. Compared with the pretreatment IMT, the results indicated that the IMT was consistently increased during therapy in the two patient groups. Patient blood pressure and concentration of troponin T increased transiently. An increase in the concentration of high-density lipoprotein cholesterol and decrease in the concentrations of C-reactive protein and homocysteine were also observed. Novel myocardial ischemia was evident in individual patients. In conclusion, anti-VEGF therapy affects the laboratory risk factors of atherosclerosis and results in an acceleration of atherosclerosis, as demonstrated by increased IMT.

• Klíčová slova
• atherosclerosis, biomarkers, intima-media thickness, single-photon emission computed tomography,
• Publikační typ
• časopisecké články MeSH

While 5-fluorouracil used as single agent in patients with metastatic colorectal cancer has an objective response rate around 20%, the administration of combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5-fluorouracil/folinic acid results in significantly increased response rates and improved survival. However, the side effects of systemic therapy such as myelotoxicity, neurotoxicity or gastrointestinal toxicity may lead to life-threatening complications and have a major impact on the quality of life of the patients. Therefore, biomarkers that would be instrumental in the choice of optimal type, combination and dose of drugs for an individual patient are urgently needed. The efficacy and toxicity of anticancer drugs in tumor cells is determined by the effective concentration in tumor cells, healthy tissues and by the presence and quantity of the drug targets. Enzymes active in drug metabolism and transport represent important determinants of the therapeutic outcome. The aim of this review was to summarize published data on associations of gene and protein expression, and genetic variability of putative biomarkers with response to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5-fluorouracil/leukovorin/irinotecan regimens. Gaps in the knowledge identified by this review may aid the design of future research and clinical trials.

• Klíčová slova
• 5-Fluorouracil, Chemotherapy, Colorectal cancer, Irinotecan, Oxaliplatin,
• MeSH
• biotransformace genetika   MeSH
• chemorezistence genetika   MeSH
• farmakogenetika * MeSH
• fenotyp MeSH
• fluoruracil aplikace a dávkování   MeSH
• individualizovaná medicína * MeSH
• irinotekan MeSH
• kamptothecin aplikace a dávkování   analogy a deriváty   MeSH
• kolorektální nádory farmakoterapie   genetika   MeSH
• leukovorin aplikace a dávkování   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• organoplatinové sloučeniny aplikace a dávkování   MeSH
• oxaliplatin MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fluoruracil MeSH
• irinotekan MeSH
• kamptothecin MeSH
• leukovorin MeSH
• nádorové biomarkery MeSH
• organoplatinové sloučeniny MeSH
• oxaliplatin MeSH

Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment. Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol.

• MeSH
• adenokarcinom farmakoterapie   imunologie   metabolismus   radioterapie   MeSH
• alfa-tokoferol krev   MeSH
• antioxidancia metabolismus   MeSH
• chromatografie plynová MeSH
• dietní sacharidy farmakokinetika   MeSH
• diterpeny MeSH
• fluoruracil škodlivé účinky   terapeutické užití   MeSH
• intestinální absorpce * účinky léků   účinky záření   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory rekta farmakoterapie   imunologie   metabolismus   radioterapie   MeSH
• neopterin moč   MeSH
• protinádorové antimetabolity škodlivé účinky   terapeutické užití   MeSH
• retinylestery MeSH
• sacharidy moč   MeSH
• senioři MeSH
• vitamin A aplikace a dávkování   analogy a deriváty   krev   farmakokinetika   MeSH
• vysokoenergetická radioterapie škodlivé účinky   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alfa-tokoferol MeSH
• antioxidancia MeSH
• dietní sacharidy MeSH
• diterpeny MeSH
• fluoruracil MeSH
• neopterin MeSH
• protinádorové antimetabolity MeSH
• retinol palmitate MeSH Prohlížeč
• retinylestery MeSH
• sacharidy MeSH
• vitamin A MeSH

BACKGROUND: Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum. METHODS: Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups. RESULTS: After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity. CONCLUSION: A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel and platinum. Increased lactulose absorption, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were evident in patients with grade 3 or 4 toxicity, and increased baseline lactulose/mannitol ratio predicted serious toxicity.

• MeSH
• adenokarcinom farmakoterapie   metabolismus   patologie   MeSH
• cisplatina aplikace a dávkování   MeSH
• dospělí MeSH
• gastrointestinální trakt metabolismus   MeSH
• humanizované monoklonální protilátky MeSH
• intestinální absorpce účinky léků   MeSH
• karboplatina aplikace a dávkování   MeSH
• laktulosa metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mannitol metabolismus   MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• nádory glandulární a epitelové farmakoterapie   metabolismus   patologie   MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• nádory vaječníků farmakoterapie   metabolismus   patologie   MeSH
• paclitaxel aplikace a dávkování   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• sacharosa metabolismus   MeSH
• senioři MeSH
• trastuzumab MeSH
• xylosa metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cisplatina MeSH
• humanizované monoklonální protilátky MeSH
• karboplatina MeSH
• laktulosa MeSH
• mannitol MeSH
• monoklonální protilátky MeSH
• paclitaxel MeSH
• sacharosa MeSH
• trastuzumab MeSH
• xylosa MeSH