Delay effects in the response of low-grade gliomas to radiotherapy: a mathematical model and its therapeutical implications

Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14, 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatmen

Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation

AIM: To investigate large tumor suppressor 1 (LATS1) expression, promoter hypermethylation, and microsatellite instability in colorectal cancer (CRC). METHODS: RNA was isolated from tumor tissue of 142 CRC patients and 40 colon mucosal biopsies of healthy controls. After reverse transcription, quantitative polymerase chain reaction (PCR) was performed, and LATS1 expression was normalized to expression of the ACTB and RPL32 housekeeping genes. To analyze hypermethylation, genomic DNA was isolated from 44 tumor CRC biopsies, and methylation-specific PCR was performed. Microsatellite instability (MSI) status was checked with PCR using BAT26, BAT25, and BAT40 markers in the genomic DNA of 84 CRC patients, followed by denaturing gel electrophoresis. RESULTS: Decreased LATS1 expression was found in 127/142 (89.4%) CRC cases with the average ratio of the LATS1 level 10.33 ± 32.64 in CRC patients vs 32.85 ± 33.56 in healthy controls. The lowest expression was found in Dukes’ B stage tumors and G1 (well-differentiated) cells. Hypermethylation of the LATS1 promoter was present in 25/44 (57%) CRC cases analyzed. LATS1 promoter hypermethylation was strongly associated with decreased gene expression; methylated cases showed 162× lower expression of LATS1 than unmethylated cases. Although high-grade MSI (mutation in all three markers) was found in 14/84 (17%) cases and low-grade MSI (mutation in 1-2 markers) was found in 30/84 (36%) cases, we found no association with LATS1 expression. CONCLUSION: Decreased expression of LATS1 in CRC was associated with promoter hypermethylation, but not MSI status. Such reduced expression may promote progression of CRC

Верификација на квалитативни методи Ñо теÑÑ‚ ленти за иÑпитување на дроги кои Ñе злоупотребуваат во урина

The verification of the  qualitative method with test  devices for detection of eight drugs of abuse in urine  (amphetamines, methamphetamine,  barbiturates,  benzoylecgonine,  marijuana, 3,4-methylendioxy-methamphetamine, methadone, and opiates) was done using the assessment results  from External Quality Assessment  Scheme according to  verification protocol in  our laboratory, which included predefined performance characteristics such as: accuracy, sensitivity and specificity of the method, as well as for method comparison analysis. Our results have shown that  qualitative methods for detection of drugs of abuse in urine have fulfilled the predefined criteria in regard to sensitivity, specificity and accuracy for screening purposes. There was a good agreement between the observed results and assessment results. Reliability of the method has fulfilled the predefined criteria with the exception for amphetamine and methamphetamine (weak and none, respectively). As a conclusion we may say that the rapid non-instrumented test devices for detection of drugs of abuse in urine have shown satisfactory verification results and have fulfilled the criteria for intended purposes according to the ISO 15189 Standard.Верификацијата на квалитативните методи Ñо брзи теÑтови за детекција на оÑум дроги кои Ñе злоупотребуваат во урината (амфетамини, метамфетамини,  Ð±Ð°Ñ€Ð±Ð¸Ñ‚урати, кокаин, марихуана,3,4-метилендиокÑи-метамфетамин, метадон и опиати) беше направена Ñо примена на резулта- тите од оценката од надворешната контрола на квалитетот, врз оÑнова на протоколот за вери- фикација во нашата лабораторија, кој опфаќа претходно дефинирани критериуми како  ÑˆÑ‚о Ñе: точноÑта, ÑензитивноÑта  Ð¸ ÑпецифичноÑта на методот. Ðашите резултати покажаа дека квалитативниот метод за детекција на дрогите кои Ñе злоупотребуваат во урина ги иÑполнува претходно дефинираните  критериуми во поглед на ÑензитивноÑта, ÑпецифичноÑта и точноÑ- та за screening потреби. ПоÑтои добро Ñовпаѓање на добиените резултати од наша Ñтрана Ñо резултатите од надвoрешната контрола на квалитет. ВеродоÑтојноÑта на методот ги иÑполни претходно дефинираните критериуми Ñо иÑклучок на амфетамините и метамфетаминот (Ñлаба, одноÑно никаква). Како заклучок можеме да кажеме дека брзите неинÑтрументални теÑтови за детекција на дроги кои Ñе злоупотребуваат во урината покажаа задоволителни резултати од верификацијата и ги иÑполнија критериумите за Ñоодветната планирана намена во ÑоглаÑноÑÑ‚ Ñо Ñтандардот ISO 15189

In vivo Antitumor and ametastatic efficacy of a polyacetal-based paclitaxel conjugate for prostate cancer therapy

Prostate cancer (PCa), one of the leading causes of cancer-related deaths, currently lacks effective treatment for advanced-stage disease. Paclitaxel (PTX) is a highly active chemotherapeutic drug and the first-line treatment for PCa; however, conventional PTX formulation causes severe hypersensitivity reactions and limits PTX use at high concentrations. In the pursuit of high molecular weight, biodegradable, and pH-responsive polymeric carriers, we conjugated PTX to a polyacetal-based nanocarrier to yield a tert-Ser-PTX polyacetal conjugate. tert-Ser-PTX conjugate provides sustained release of PTX over two weeks in a pH-responsive manner while also obtaining a degree of epimerization of PTX to 7-epi-PTX. Serum proteins stabilize tert-Ser-PTX, with enhanced stability in human serum vs. PBS (pH 7.4). In vitro efficacy assessments in PCa cells demonstrated IC50 values above those for the free form of PTX due to the differential cell trafficking modes; however, in vivo tolerability assays demonstrated that tert-Ser-PTX significantly reduced the systemic toxicities associated with free PTX treatment. tert-Ser-PTX also effectively inhibited primary tumor growth and hematologic, lymphatic, and coelomic dissemination, as confirmed by in vivo and ex vivo bioluminescence imaging and histopathological evaluations in mice carrying orthotopic LNCaP tumors. Overall, our results suggest the application of tert-Ser-PTX as a robust anti-tumor/antimetastatic treatment for PCa

Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD

Comics and Politics

Medea Vox, an academic podcast. Episode 24: Comics have been around for more than a hundred years. For a long time, comics were mainly viewed as light entertainment for kids, but today they can also be seen as an aesthetically ambitious art form. But are comics also a politically significant medium? In this Medea Vox episode, comics artist Daria Bogdanska and professor Magnus Nilsson talk about comics and politics. Can comics be used to criticize and think about society in new ways? Can comics articulate new voices, or reach out to those who are not taking part in political life? And which are the potentials and limitations of comics as a political art form

Comics and Politics

Medea Vox, an academic podcast. Episode 24: Comics have been around for more than a hundred years. For a long time, comics were mainly viewed as light entertainment for kids, but today they can also be seen as an aesthetically ambitious art form. But are comics also a politically significant medium? In this Medea Vox episode, comics artist Daria Bogdanska and professor Magnus Nilsson talk about comics and politics. Can comics be used to criticize and think about society in new ways? Can comics articulate new voices, or reach out to those who are not taking part in political life? And which are the potentials and limitations of comics as a political art form?Podcas