Methamphetamine, mainly consumed as an illicit drug, is a potent addictive psychostimulant that has been detected in surface water at concentrations ranging from nanograms to micrograms per litre, especially in Middle and East Europe. The aim of this study was to expose brown trout (Salmo trutta fario) to environmental (1 μg L-1) and higher (50 μg L-1) concentrations of methamphetamine for 35 days with a four-day depuration phase to assess the possible negative effects on fish health. Degenerative liver and heart alterations, similar to those described in mammals, were observed at both concentrations, although at different intensities. Apoptotic changes in hepatocytes, revealed by activated caspase-3, were found in exposed fish. The parent compound and a metabolite (amphetamine) were detected in fish tissues in both concentration groups, in the order of kidney > liver > brain > muscle > plasma. Bioconcentration factors ranged from 0.13 to 80. A therapeutic plasma concentration was reached for both compounds in the high-concentration treatment. This study indicates that chronic environmental concentrations of methamphetamine can lead to health issues in aquatic organisms.

• MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• játra metabolismus   MeSH
• ledviny patologie   MeSH
• methamfetamin toxicita   MeSH
• pstruh metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.

• MeSH
• biologické markery MeSH
• dendritické buňky imunologie   metabolismus   patologie   MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• imunohistochemie MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom imunologie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory vaječníků imunologie   mortalita   patologie   terapie   MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• T-lymfocyty - podskupiny imunologie   metabolismus   patologie   MeSH
• tumor infiltrující lymfocyty imunologie   metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Detection of HPV in the oropharyngeal cancer prior to treatment selects the group of HPV positive and negative patients. In both groups a treatment response and survival rate for various treatment modalities (chemotherapy, radiotherapy, chemoradiotherapy, biological treatment with monoclonal antibodies, surgery) will be analysed. We would determine whether the prognostic advantage of patients with HPV positive tumours is treatment modality dependent. We suppose, that HPV positive patients could benefitfrom a less intensive non-surgical therapy with an equal survival rate. HPV status could soon become a tool for treatment individualisation. Direct (HPV DNA, HPV mRNA of E6 and E 2 genes) and indirect (p53, p16 proteins) markers of an active viral infection will be detected and sensitivity of HPV DNA detection by means of ISH and PCR would be compared. With the aim to find out the optimal diagnostic method for selection of patients with HPV related head and neck cancers in clinical setting.

Stanovení HPV ve vzorku orofaryngeálního dlaždicobuněčného karcinomu před léčbou selektuje skupinu pacientů s HPV pozitivními a negativními nádory. V obou skupinách bude zjišťována léčebná odpověď a přežití v závislosti na léčebných modalitách (chemoterapie, radioterapie, chemoradioterapie, biologická léčba monoklonální protilátkou, chirurgie). Bude zkoumáno, zda prognostická výhoda HPV pozitivity je vázána na způsob léčby. Předpokládáme, že HPV pozitivní pacienti by do budoucna mohli profitovat z méněintenzivní konzervativní terapie při zachování stejné prognózy. HPV status by se v krátkém časovém horizontu mohl stát významným nástrojem pro stratifikaci léčby. Detekovány budou přímé (HPV DNA, HPV mRNA genu E6 a E2) a nepřímé (exprese proteinů p53 a p16) markery aktivní virové infekce a bude srovnána senzitivita metod stanovujících přítomnost HPV DNA -PCR a ISH. Účelem je zjištění optimální diagnostické metody pro klinickou praxi k selekci pacientů s HPV pozitivními nádory hlavy a krku.

• MeSH
• DNA testy na papilomavirus MeSH
• infekce DNA virem MeSH
• infekce papilomavirem MeSH
• interpretace statistických dat MeSH
• nádory hlavy a krku MeSH
• nádory orofaryngu MeSH
• polymerázová řetězová reakce MeSH
• prognóza MeSH
• spinocelulární karcinom MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• otorinolaryngologie
• onkologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV-specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty-two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV-specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV-specific antibodies in the sera. Out of 66 patients with HPV-positive oral rinses at enrolment, 84.8% became negative at one-year follow-up, while most patients remained seropositive for HPV-specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow-up were significantly lower. Of 16 patients with recurrences at follow-up (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow-up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV-positive tumors.

• MeSH
• DNA virů izolace a purifikace   MeSH
• infekce papilomavirem * krev   genetika   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 imunologie   MeSH
• míra přežití MeSH
• nádorové biomarkery MeSH
• nádory hlavy a krku mortalita   virologie   MeSH
• onkogenní proteiny virové imunologie   MeSH
• Papillomavirus E7 - proteiny imunologie   MeSH
• prognóza MeSH
• protilátky virové krev   MeSH
• represorové proteiny imunologie   MeSH
• ústa virologie   MeSH
• virové plášťové proteiny imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH