Antitumor effect of PEG-ZnPP in rat glioma cells, F98 and C6, and in rat brainstem tumor models

Objective: Brainstem tumors account for about 10-20% of all primary paediatric tumors in the central nervous system. Approximately 75% of all brainstem tumors in children are diffuse pontine gliomas (DIPG) and the median overall survival is less than a year. Due to its infiltrative character and anatomical location, surgical resection is not considered as therapeutic option. It was described that expression of HO-1 is associated with growth activity of cancer cells, which suggests that a specific inhibitor of HO-1, ZnPP, may work as a potent antitumor therapeutic agent. To evaluate the antitumor efficacy of PEG-ZnPP, a water soluble derivate of ZnPP, we performed studies in vitro and in vivo brainstem glioma models. Methods: To evaluate the antitumor efficacy of PEG-ZnPP in vitro, proliferation assay on glioma cell lines C6 and F98 was performed. Based on the results of our proliferation assay, apoptotic activity using conjugate of annexin V was evaluated and cell cycle analysis was assessed. After in vitro study, we performed systemic therapy with PEG-ZnPP in rat brainstem tumor models with F98 and C6. Neurological status and survival rate was monitored. Results: This project demonstrated that PEG-ZnPP significantly inhibits rat glioma cell proliferation and induces a significant level of apoptosis in C6 and F98 glioma cell lines, suggesting that PEG-ZnPP may represent a potential anticancer agent for brain tumors. In vivo study on rat brainstem glioma models, however, showed no differences of survival between the control group and animals receiving intravenous PEG-ZnPP therapy. Conclusion: In contrast to in vitro studies systemic administration of PEG-ZnPP did not improve the survival on the rat brainstem glioma model suggesting that different approaches and additional animal research are required to overcome the BBB and to further investigate the potential anticancer abilities of PEG-ZnPP.Einleitung: Tumore des Hirnstamms machen ca. 10-20% aller primären Tumoren des zentralen Nervensystems im Kindesalter aus. Zirka 75% aller Tumore im Hirnstamm sind die diffus intrinsischen Ponsgliome (DIPG) und deren mediane Lebenserwartung beträgt weniger als ein Jahr. Aufgrund des infiltrativen Charakters und deren Lokalisation kommt die Resektion als therapeutische Option nicht in Frage. Es ist bekannt, dass erhöhte Expression der HO-1 mit einem raschen Wachstum von Tumorzellen assoziiert ist, sodass eine spezifische Inhibition der HO-1 mittels PEG-ZnPP, eine wasserlösliche Form von ZnPP, als eine anti-tumorale Therapie möglich erscheinen lässt. In dieser Studie wurde antitumorale Wirkung von PEG-ZnPP innerhalb von in vitro Analyse und in vivo im Hirnstammgliom Modell bei der Ratte durchgeführt. Methoden: In der vitro Untersuchung erfolgte zur Evaluation der antitumoren Effektivität eine Proliferationsanalyse in den F98 und C6 Gliomzelllinien. Anschließend erfolgte in einer vivo Studie die Implantation von F98 und C6 Gliomzellen in den Hirnstamm der Ratte gefolgt von einer systemischen Gabe von PEG-ZnPP. Der neurologische Status und das Körpergewicht der Ratte wurden im Verlauf dokumentiert und die Überlebensrate der Tiere bestimmt. Ergebnisse: Diese Studie konnte in den in-vitro Untersuchungen die signifikante Hemmung der Gliomzell-Proliferation durch PEG-ZnPP zeigen. Demgegenüber zeigten die in-vivo Untersuchungen keine Unterschiede der Überlebensrate der PEG-ZnPP behandelten Tiere im Vergleich zu den Kontrolltieren. Schlussfolgerung: Trotz der antitumoralen Wirkung von PEG-ZnPP in vitro zeigte die systemische Applikation im Hirnstammgliom Modell keine überlebensverlängernde Wirkung der Ratte. Am ehesten scheint die Blut-Hirn-Schranke eine relevante Barriere für PEG ZnPP zu sein welches diese Diskrepanz erklären könnte. Als Herausforderung bleibt neue Versuchsverfahren zur Überwindung der Blut-Hirn-Schranke zu finden, um die antitumore Wirksamkeit von PEG-ZnPP in-vivo testen zu können

Efficacy of endoscopic third ventriculostomy in old aged patients with normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a chronic disorder caused by interrupted CSF absorption or flow. Generally, shunt placement is first option for NPH treatment. Due to complications of ventriculo-peritoneal (VP) shunt placement, endoscopic third ventriculostomy (ETV) can be considered as an alternative treatment option. Here we report the efficacy of ETV especially in old aged patients with normal pressure hydrocephalus. Total 21 old aged patients with communicating hydrocephalus with opening pressure, measured via lumbar puncture, less than 20cm H2O underwent ETV. 15 patients had primary/idiopathic NPH and 6 patients had secondary NPH. All patients were studied with a MRI to observe the flow void at aqueduct and the fourth ventricle outflow. And all of them underwent ETV. In a group with peak velocity was higher than 5cm/s, nine patients (75%) were evaluated was ‘favorable’ and three of them (25%) was scored ‘poor’. In another group with peak velocity less than 5cm/s, three of them were scored ‘poor’ and two of them were scored ‘stable’. None of them was evaluated as ‘favorable’. We also evaluated the outcomes according to etiology: 12 patients (80% of the patients with primary NPH) were evaluated with ‘favorable’ after ETV treatment. Two patients (13.3%) were as ‘stable’. And one patient was as ‘poor’ evaluated. Five patients (83.3%) among patients with secondary NPH were as ‘poor’ evaluated and one of them was stable and no patient was as ‘favorable’ evaluated. 4 patients, which was as ‘poor’ evaluated in the group with the secondary NPH, underwent additional VP shunt implantation. Overall, the outcomes of the group with the idiopathic NPH after ETV treatment were more favorable than of the group with the secondary NPH. Our study suggest that ETV can be effective for selected elderly patients with primary/idiopathic NPH, when they satisfy criteria including positive aqueduct flow void on T2 Sagittal MRI and the aqueductal peak velocity, which is greater than 5cm/s on cine MRI

In Vivo Biocompatibility Study of Electrospun Chitosan Microfiber for Tissue Engineering

In this work, we examined the biocompatibility of electrospun chitosan microfibers as a scaffold. The chitosan microfibers showed a three-dimensional pore structure by SEM. The chitosan microfibers supported attachment and viability of rat muscle-derived stem cells (rMDSCs). Subcutaneous implantation of the chitosan microfibers demonstrated that implantation of rMDSCs containing chitosan microfibers induced lower host tissue responses with decreased macrophage accumulation than did the chitosan microfibers alone, probably due to the immunosuppression of the transplanted rMDSCs. Our results collectively show that chitosan microfibers could serve as a biocompatible in vivo scaffold for rMDSCs in rats

Measurement of the polar-angle distribution of leptons from W boson decay as a function of the W transverse momentum in proton-antiproton collisions at sqrt{s}=1.8 TeV

We present a measurement of the coefficient alpha_2 of the leptonic polar-angle distribution from W boson decays, as a function of the W transverse momentum. The measurement uses an 80+/-4 pb^{-1} sample of proton-antiproton collisions at sqrt{s}=1.8 TeV collected by the CDF detector and includes data from both the W->e+nu and W->mu+nu decay channels. We fit the W boson transverse mass distribution to a set of templates from a Monte Carlo event generator and detector simulation in several ranges of the W transverse momentum. The measurement agrees with the Standard Model expectation, whereby the ratio of longitudinally to transversely polarized W bosons, in the Collins-Soper W rest frame, increases with the W transverse momentum at a rate of approximately 15% per 10 GeV/c.Comment: 47 pages, 16 figures, submitted to Physical Review

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació