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

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu chemie   farmakoterapie   mortalita   patologie   MeSH
• neoadjuvantní terapie MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• receptor erbB-2 analýza   MeSH
• receptory pro estrogeny analýza   MeSH
• receptory progesteronu analýza   MeSH
• retrospektivní studie MeSH
• senioři 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
• ERBB2 protein, human MeSH Prohlížeč
• receptor erbB-2 MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH

An increased incidence of complications of atherosclerosis has been noted in cancer survivors. The aim of the present study was to evaluate, in patients with breast carcinoma, the effect of antracycline-based chemotherapy on carotid intima-media thickness (IMT), myocardial perfusion, assessed by single-photon emission tomography (SPECT) and laboratory parameters associated with the risk of atherosclerosis. Thirty-six patients with breast cancer were evaluated before and after anthracycline-based chemotherapy. Retinol, alpha-tocopherol, glycosylated hemoglobin and urinary neopterin were measured by high-performance liquid chromatography. Peripheral blood cell count, D-dimers, fibrinogen, antithrombin, glucose, magnesium, creatinine, uric acid, albumin, C-reactive protein, lipoprotein (a), cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, homocysteine, urinary albumin and N-acetyl-beta-D-glucosaminidase (NAG) were determined with routine methods. No significant differences were observed between patients and 16 controls. Compared to the measurement before the start of therapy, peripheral blood leukocyte and platelet count, hemoglobin, creatinine, HDL cholesterol, retinol, albumin, urinary albumin and NAG decreased, and total cholesterol, LDL cholesterol, triglycerides, neopterin and mean IMT increased significantly after the treatment. Of the 36 patients who had SPECT after treatment, perfusion defects were noted only in two cases, including the patient who had perfusion defects at baseline examination and a patient who did not have a baseline SPECT. In conclusion, a significant increase in carotid IMT, total cholesterol, LDL cholesterol, triglycerides and urinary neopterin and a decrease of peripheral blood leukocyte and platelet counts, hemoglobin, creatinine, HDL cholesterol, retinol, albumin and NAG were observed after the treatment.

• MeSH
• antracykliny škodlivé účinky   MeSH
• ateroskleróza krev   komplikace   epidemiologie   MeSH
• dospělí MeSH
• intimomediální šíře tepenné stěny MeSH
• jednofotonová emisní výpočetní tomografie MeSH
• karcinom komplikace   farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard patologie   MeSH
• nádory prsu komplikace   farmakoterapie   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• rizikové faktory MeSH
• tunica intima patologie   MeSH
• tunica media patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antracykliny 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