O glioblastoma multiforme (GBM) é a forma mais maligna de tumor cerebral, originado de células astrocíticas e caracterizado pela intensa proliferação, angiogênese e invasão celular pelo parênquima cerebral normal. O ácido gama-linolênico (GLA) mostrou ter ações anti-tumorais, nos processos de proliferação, migração e angiogênese. Utilizou-se o modelo ortotópico de GBM de rato (C6) e o modelo ex vivo tratados com GLA para análise de migração e proliferação celular. Foi observada uma redução da imunomarcação do fator de crescimento para endotélio vascular (VEGF), seu receptor Flt-1 e da metaloproteinase-2 de matriz, com consequente diminuição de vasos após o tratamento com GLA. No modelo ex vivo observou que o GLA reduziu a distância de migração e a mitose das células tumorais e também causou aumento das células tumorais em processo de apoptose. Os resultados revelaram que o GLA foi capaz de modular a expressão de algumas proteínas envolvidas nos processos angiogênico, migratório e proliferativo do GBM, o que sugere a sua utilização no tratamento desta patologia. / Glioblastoma multiforme (GBM) is the most malignant form of brain tumour originating from astrocytes and is characterized by intense proliferation, angiogenesis and cell invasion through the normal brain parenchyma. Gamma-linolenic acid (GLA) has anti-tumour activities in the processes of proliferation, migration and angiogenesis. This study used the orthotopic GBM rat model (C6) and ex vivo model treated with GLA to analyze cell migration and proliferation. Decreased immunostaining was observed for vascular endothelial growth factor (VEGF), its receptor Flt-1 and matrix metalloproteinase-2, with consequent reduction of blood vessels after treatment with GLA. In the ex vivo model GLA reduced the migration distance and mitosis of tumor cells and increased tumour cell apoptosis. The results revealed that GLA was able to modulate the expression of several proteins involved in angiogenesis, migration and proliferation in GBM, supporting the use of GLA in the treatment of this disease.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-02-07T19:19:35Z No. of bitstreams: 1 Lizandra Moreira Góes... Caracterização dos efeitos tóxicos....pdf: 1602592 bytes, checksum: 16b9153b36fb34585abb21b40bd4bdef (MD5) / Made available in DSpace on 2014-02-07T19:19:35Z (GMT). No. of bitstreams: 1 Lizandra Moreira Góes... Caracterização dos efeitos tóxicos....pdf: 1602592 bytes, checksum: 16b9153b36fb34585abb21b40bd4bdef (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Catecóis são derivados do benzeno, podendo apresentar citotoxicidade, que pode constituir um modelo experimental útil para o desenvolvimento de novos fármacos. No bioma brasileiro inúmeras plantas produzem metabólitos com atividades diversas, como antioxidantes, ou inibidores do crescimento celular. No Brasil, as neoplasias são a segunda causa de óbito, especialmente aquelas derivadas do sistema nervoso, aumentando o interesse por novos antineoplásicos e agentes neuroprotetores. Este trabalho caracteriza efeitos citotóxicos do 1,2-dihidroxibenzeno (CAT) e discretamina (DSC) em células do sistema nervoso in vitro. Determinou-se a EC50 de CAT e DSC usando brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium (MTT), investigou-se sua auto-oxidação por espectrofotometria, avaliou-se mudanças morfológicas e condensação/fragmentação nuclear por microscopia. Avaliou-se a proteção de DSC e 8-metoxipsoraleno (8-MOP) contra a citotoxicidade do CAT. O padrão de morte celular foi analisado por citometria de fluxo. A espoliação de glutation reduzido (GSH) foi analisada usando monoclorobimano. A toxicidade do CAT para células SH-SY5Y e C6 depende da dose e associa-se à formação de quinonas. Houve mudanças morfológicas, condensação/fragmentação da cromatina e morte apoptótica, não relacionada à espoliação de GSH. DSC não foi tóxica para células SH-SY5Y, porém protegeu contra os efeitos do CAT em baixas concentrações. DSC mostrou-se citotóxica para células de glioma (GL-15 e C6) e potencializou o CAT. Pré-tratamento por 30 minutos com DSC protegeu contra a ação do CAT após 72 horas. 8-MOP potencializou os efeitos do CAT, não revertendo seus efeitos na viabilidade celular, morfologia celular, condensação/fragmentação nuclear, e espoliação de GSH. Esses resultados caracterizam um modelo de citotoxicidade que pode ser aplicado no desenvolvimento de novos agentes farmacológicos. Estudos complementares são necessários para elucidar a proteção da DSC. / Catechols are benzene derivatives, which may exhibit cytotoxic activity that can be employed to develop new drugs. Plants are important sources of metabolites with pharmacological activities such as antioxidants, or cell growth inhibitors. In Brazil, cancer is the second leading cause of death, especially those derived from the nervous system, which increase the interest for new antineoplastic and neuroprotective drugs. The cytotoxic effects promoted by 1,2-dihydroxybenzene (CAT) and discretamine (DSC) in nervous system cells were characterized in vitro. The protective effects of DSC and 8-methoxypsoralen (8-MOP) against CAT-induced cytotoxicity were also evaluated. CAT and DSC EC50 was determined by using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT). CAT auto-oxidation was investigated by spectrophotometry. Morphological changes and nuclear condensation/ fragmentation were evaluated by microscopy. The pattern of cell death was obtained by flow cytometry. Reduced glutathione (GSH) depletion was analyzed by using monochlorobimane. CAT induced a dose-dependent toxicity to SH-SY5Y and C6 cells, associated with reactive quinones formation. It also induced morphological changes, nuclear condensation/fragmentation, and apoptotic death not caused by GSH depletion. DSC was not toxic to SH-SY5Y cells, but protected against CAT effects at low concentrations. DSC was be cytotoxic to glioma cells (GL-15 and C6) and potentiated CAT effects. However, pretreatment for 30 minutes with DSC protected them against CAT after 72 hours. 8-MOP also potentiated CAT effects instead to protect cells. These results characterize an experimental model useful for studies searching new pharmacological agents. However, further studies are needed to elucidate the DSC protective effects.

O glioblastoma multiforme (GBM) é a forma mais maligna de tumor cerebral, originado de células astrocíticas e caracterizado pela intensa proliferação, angiogênese e invasão celular pelo parênquima cerebral normal. O ácido gama-linolênico (GLA) mostrou ter ações anti-tumorais, nos processos de proliferação, migração e angiogênese. Utilizou-se o modelo ortotópico de GBM de rato (C6) e o modelo ex vivo tratados com GLA para análise de migração e proliferação celular. Foi observada uma redução da imunomarcação do fator de crescimento para endotélio vascular (VEGF), seu receptor Flt-1 e da metaloproteinase-2 de matriz, com consequente diminuição de vasos após o tratamento com GLA. No modelo ex vivo observou que o GLA reduziu a distância de migração e a mitose das células tumorais e também causou aumento das células tumorais em processo de apoptose. Os resultados revelaram que o GLA foi capaz de modular a expressão de algumas proteínas envolvidas nos processos angiogênico, migratório e proliferativo do GBM, o que sugere a sua utilização no tratamento desta patologia. / Glioblastoma multiforme (GBM) is the most malignant form of brain tumour originating from astrocytes and is characterized by intense proliferation, angiogenesis and cell invasion through the normal brain parenchyma. Gamma-linolenic acid (GLA) has anti-tumour activities in the processes of proliferation, migration and angiogenesis. This study used the orthotopic GBM rat model (C6) and ex vivo model treated with GLA to analyze cell migration and proliferation. Decreased immunostaining was observed for vascular endothelial growth factor (VEGF), its receptor Flt-1 and matrix metalloproteinase-2, with consequent reduction of blood vessels after treatment with GLA. In the ex vivo model GLA reduced the migration distance and mitosis of tumor cells and increased tumour cell apoptosis. The results revealed that GLA was able to modulate the expression of several proteins involved in angiogenesis, migration and proliferation in GBM, supporting the use of GLA in the treatment of this disease.

Flavonoids are a class of plant metabolites with C6-C3-C6 structure responsible for many biological functions, including coloration and defense. Citrus paradisi, grapefruit, contains a wide variety of flavonoids which are grouped by the extent of modification, examples of which are flavonols, flavones, and flavanones. A major modification is the addition of glucose by glucosyltransferases (GTs) to stabilize the structure and provide ease of transport. This process can be highly substrate and regiospecific. With Cp3OGT, glucose is added at the 3-hydroxy position. This 3GT only accepts flavonols as its substrate; however, a Vitis vinifera (grape) 3-GT can accept both flavonols and anthocyanidins. Homology modeling using the crystallized structure of the V. vinifera GT predicted sites of amino acids that could influence substrate binding site. The 382 position was of particular interest with arginine in C. paradisi and tryptophan in V. vinifera. This change is hypothesized to cause a shift in substrate specificity of the Cp3OGT to accept anthocyanidins as well as flavonols. Site-directed mutagenesis was performed to form the R382W mutant Cp3OGT and transformed into yeast for expression. Western blot determined the optimal protein induction period for the cells, after which the cells were broken to extract the recombinant mutant protein. Purification of the R382W 3GT allowed for enzyme analysis to be performed by measuring the incorporation of radioactive glucose into the reaction product. HPLC will be used to identify reaction products. An enzyme kinetics study will show the extent of any biochemical change in function as a result of this mutation; results will then be incorporated into a refined protein model.

Borrelios är den vanligaste fästingburna infektionen på norra halvklotet, och orsakas av spiroketer tillhörande Borrelia burgdorferi sensu lato-komplexet. Dessa bakterier kan spridas till flera organ och ge upphov till olika symptom i bland annat hud, nervsystem, leder och hjärta. Omkring 15 % utvecklar neurologiska symptom, så kallad neuroborrelios. Den bästa indikatorn på aktiv neuroborrelios är framförallt karakteristiska neurologiska symptom samt tecken på en inflammatorisk förändring i cerebrospinalvätskan (CSV) i kombination med lokalt producerade antikroppar mot Borrelia burgdorferi s.l. i CSV. Nuvarande metod för diagnostik av neuroborrelios är en immunokemisk metod, en ELISA (enzyme-linked immunosorbent assay) som bygger på en jämförelse av Borrelia-antikroppsnivåer i CSV och i serum genom beräkning av antikroppsindex (AI). Beräkning av AI kompenserar för en eventuell ospecifik överföring av antikroppar från serum, till följd av en skada på blod-hjärnbarriären. Det finns dock tecken på att den nuvarande analysmetoden har för låg sensitivitet med falskt negativa resultat, framförallt tidigt i infektionsförloppet. För diagnostik av andra former av borrelios än neuroborrelios används en typ av ELISA baserad på C6-peptid. C6-peptid ELISA visar god känslighet för detektion av B. burgdorferi s.l.-specifika antikroppar i serum. C6-antigenet utgör en starkt immunogen och konserverad region av bakteriens VlsE-ytprotein. Syftet med den här studien var att undersöka om detektion av antikroppar mot C6-peptid i CSV kan komplettera den nuvarande använda metoden och därmed förbättra den totala sensitiviteten för diagnostik av neuroborrelios. I studien analyserades 169 patientprover från unga personer, samt 18 oklara patientfall som tidigare bedömts negativa med den nuvarande metoden. Antikroppar mot C6-peptid detekterades hos åtta unga patienter samt två oklara patientfall. Av dessa hade åtminstone tre unga patienter sannolikt neuroborrelios. Resultat från den här studien tyder på att C6-peptid-ELISA på CSV-prover kan fungera som ett komplement till befintlig metod för diagnostik av neuroborrelios. En kombination av båda metoderna kan sannolikt ge en betydligt högre sensitivitet. Vid tolkning av resultat från C6-peptid-baserade analysmetoder på CSV ska hänsyn tas till eventuell ospecifik överföring av B. burgdorferi s.l.-specifika antikroppar genom blod-hjärnbarriären. / Lyme Borreliosis, caused by spirochetes of the Borrelia burgdorferi sensu lato-complex, is the most common tick-borne infection in the temperate regions of the northern hemisphere. The bacteria can infect many different organs, this can give rise to a variety of symptoms in skin, the nervous system, joints and heart. Approximately 15 % of the infected individuals show neurological symptoms referred to as neuroborreliosis. An active neuroborreliosis is indicated by inflammatory changes in the cerebrospinal fluid (CSF) and local synthesis of anti-Borrelia antibodies in CSF. The current method to diagnose neuroborreliosis is an enzyme-linked immunosorbent assay (ELISA) which compares levels of anti-Borrelia antibodies in CSF and serum by calculating an antibody index (AI). Calculations of AI compensate for unspecific leakage of antibodies from serum to CSF following an injury of the blood-brain barrier. The drawback of the current method is a low sensitivity with a high rate of false negative results in samples collected early during an infection. Another type of ELISA, based on the use of a C6 peptide, has earlier shown good sensitivity for detection of B. burgdorferi s.l.-specific antibodies in serum. The C6 antigen corresponds to a highly immunogenic and conserved region of the bacterial surface protein VlsE. The aim of this study was to investigate whether a detection of antibodies against the C6 peptide in CSF could improve the total sensitivity for the diagnostics of neuroborreliosis. In the current study, 169 samples with negative AI from young patients and 18 samples from special cases were analyzed. Antibodies against the C6 peptide were found in 8 young patients and in 2 samples from special cases. Out of these, 3 young patients were stated positive for neuroborreliosis. Results of this study show that the C6 peptide ELISA on CSF samples could act as a complement to the current serological method for diagnosing neuroborreliosis. A combination of both methods could possibly increase the overall sensitivity. However, the blod-brain barrier injury issue is a problem in the analysis and interpretation of the results of the C6 peptide-based method on CSF should take into consideration a possible dysfunction of the blood-brain barrier. In conclusion, a combination of both the current method and the C6 peptide ELISA could give a markedly improved sensitivity in diagnostics of neuroborreliosis.

Wound dressing plays an important role in wound recovery and collagen interacts with the human body in such a way that it has specific advantages compared to synthetic materials. The aim of the present study was to get an optimal crosslinking agent for collagen and so the mechanical, chemical and biochemical properties of crosslinked collagen materials were investigated. Fibroblast cells are important in the process of wound healing, so the interaction of human fibroblast cells with crosslinked collagen films were investigated as well. Collagen I was isolated from bovine achilles tendons and collagen films were formed using the isolated collagen I solution. Collagen films were crosslinked with glutaraldehyde (GA), genipin, hexamethylenediisocyanate (HMDC), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) at the equal concentration of 0.02 M and these crosslinked collagen films were compared with uncrosslinked collagen films (control). The surfaces of the crosslinked films were investigated using scanning electron microscopy (SEM). There was observable fibre structure on GA- and genipin-crosslinked collagen films. The tensile strength, elongation at break and low strain modulus of the crosslinked collagen films were investigated. The results showed that GA-, genipin- and HMDC-crosslinked collagen films obtained higher tensile strength than the control. Elongation at break of all the crosslinked collagen films became lower than the control. GA- and genipin-crosslinked collagen films obtained higher low strain modulus than other crosslinked collagen films and the control. The denaturation temperatures of all crosslinked collagen films were significantly higher than the control and the denaturation temperatures of GA- and genipin-crosslinked films were much higher than those of HMDC- and EDC-crosslinked films. All the crosslinked collagen films were resistant to the digestion of collagenase. These results suggest that all the crosslinking agents are effective and GA- and genipin-crosslinked films obtained more extensive crosslinking. The interaction of crosslinked collagen films with fibroblast cells was investigated, e.g. adhesion, proliferation and migration of fibroblast cells. The results demonstrated that the control, genipin- and EDC-crosslinked collagen films were conducive to cell adhesion. Fibroblast cells on the control, genipin- and EDC-crosslinked collagen films were able to proliferate after 24 hours, with increased growth after 48 hours. The fibroblast cells on the control, genipin- and EDC-crosslinked collagen films migrated directionally. The cells on genipin-crosslinked film initiated directional migration earlier than those on control- and EDC-crosslinked films. In summary, genipin crosslinked collagen films show high denaturation temperature, higher tensile strength and good biocompatibility for fibroblast cells adhesion, proliferation and migration. Genipin should be regarded as a suitable crosslinking agent for reconstituted collagen for use in wound dressing.

Association rule mining is one of the most popular data mining methods. However, mining association rules often results in a very large number of found rules, leaving the analyst with the task to go through all the rules and discover interesting ones. Sifting manually through large sets of rules is time consuming and strenuous. Although visualization has a long history of making large amounts of data better accessible using techniques like selecting and zooming, most association rule visualization techniques are still falling short when it comes to large numbers of rules. In this paper we introduce a new interactive visualization method, the grouped matrix representation, which allows to intuitively explore and interpret highly complex scenarios. We demonstrate how the method can be used to analyze large sets of association rules using the R software for statistical computing, and provide examples from the implementation in the R-package arulesViz. (authors' abstract)

Vegetable tannins used in tanning of hides and skins are limited to surface reactions by their large molecular weights. The molecular weight reduces penetration into the skin and lowers the thermal stability or tanning effect. Investigation into the utilisation of small phenolic compounds such as catechin to improve penetration with subsequent in situ enzymecatalysed polymerisation may provide a novel and alternative tanning agent. In this research, catechin was oxidised by enzymatic catalysis using laccase, with the polymerisation confirmed by FT-IR and UHPLC. Tanning experiments were undertaken to measure the effect of laccase-catalysed polymerisation of catechin in the thermal stabilisation of collagen, by monitoring the change in shrinkage temperature between the treated and untreated sample of hide powder (ΔTs). This study demonstrates that the stabilisation of collagen (ΔTs) is increased with the use of in situ enzyme-catalysed polymerisation. Depolymerisation of condensed tannins is presented as an alternative source of low molecular weight phenolics to be applied in the stabilisation of collagen. In this research, mimosa tannin from the Black Wattle tree (Acacia mearnsii) was used in the depolymerisation process. Preliminary experiments on depolymerisation were undertaken using the methods laccase-mediator system and L-cysteine in mild acidic medium, both showing unsatisfactory results. Acid-catalysed depolymerisation followed by nucleophile addition is a common analytical method for determining the degree of polymerisation of proanthocyanidins. The acid-catalysed depolymerisation method was scaled-up, with the addition of pyrogallol as a nucleophile trapping agent, and powdered depolymerised mimosa was obtained. Data show an increase in the monomeric content and decrease in percentage of condensed tannins for the acid-catalysed process, indicating the potential of the depolymerisation of mimosa tannin in obtaining environmentally friendly sources of low molecular weight phenolic compounds for use in large scale/industrial applications. The depolymerised product was applied in the stabilisation of hide powder and goat skin. Using hide powder, data show that the laccase-assisted polymerisation of the depolymerised mimosa reached higher values of ΔTs in comparison with the conventional process employing unmodified mimosa. Using goat skin, the new process achieved similar values of ΔTs as the conventional process. In order to obtain similar results for goat skin as obtained with hide powder, an optimisation may be carried out. Therefore, data obtained demonstrates the potential of the new route in vegetable tanning of leather.

Chinese parental involvement in children‘s learning has been regarded as one of the key factors in accounting for their children‘s superior academic success. Chinese cultural ideologies which highlight the value of learning and parents‘heightened role in children‘s learning may shape Chinese parental involvement. The first goal of the current research was to understand Chinese parental involvement by developing a scale. The second goal was to examine the factors which influenced Chinese parental involvement. Four parental beliefs were tested: parental self-efficacy for helping the child succeed in school, parental value of academic success, parental educational aspiration and expectation for child and parental role belief in children‘s learning in children‘s learning. Children‘s academic performance was also tested as antecedent. Third, the study attempted to examine the effects of Chinese parental involvement on children‘s academic (i.e., children‘s motivational outcomes and academic achievement) and emotional functioning (i.e., life satisfaction). / A total of 323 7th graders and one of their parents participated. Children reported the involvement of their participating parents, as well as their motivational outcomes (i.e., children‘s value of academic success, relative autonomy in pursing academics, self-regulated learning strategies) and life satisfaction at Time 1 and Time 2(abbreviation for T1 and T2, 6 months apart); and children‘s grades were obtained from school records. Parents reported on their involvement in children‘s learning as well as parental beliefs in children‘s learning at T1. / The current research found that Chinese parental involvement not only included teacher initiated school-based involvement, help with schoolwork, cognitive-intellectual involvement, academic socialization regarding current learning, academic socialization regarding future academic goals which have been identified in Western countries, but also included parent initiated school-based involvement, providing a good environment, setting family rules, extra learning, reinforcement/punishment which were also important in Chinese context but have been neglected in previous work. Both parental beliefs and children‘s academic performance were related to Chinese parental involvement. Specifically, four parental beliefs differed in their contributions to various types of involvement. Children‘s academic achievement at T1 positively predicted child-reported parental help with schoolwork and providing a good environment but negatively predicted reinforcement/punishment at T2. Concurrent results (T1) demonstrated that child-reported parental involvement was significantly related to children‘s academic and emotional functioning with the effects varying by types of parental involvement. Specifically, child-reported parental academic socialization regarding current learning was positively associated with children‘s motivational outcomes. However, parental reinforcement/punishment was negatively associated with relative autonomy. Parental providing a good environment positively correlated with children‘s life satisfaction but was not related to children‘s academic outcomes. / Taken together, the study underscores the importance of studying various types of parental involvement practices in understanding Chinese parental involvement. Findings of the current study also highlight the role of parental beliefs and children‘s academic performance in parental involvement. / 中國的家長參與子女學業是造就中國學生優異成績的重要因素之一。中國文化重視學習以及家長在孩子學習中的作用，這些文化觀念會塑造中國家長參與的特點。西方的關於家長參與的理論框架可能不足以讓我們理解中國的家長參與。因此，本研究的第一個目的在於通過編制中國家長參與量表來研究中國家長參與的結構。第二個目的是探討中國家長參與的影響因素：家長的信念以及子女的學業成績。基於信念指導行為的假設，探討了家長的信念包括家長對於輔導子女學業的效能感、家長對學業的價值、家長對子女的期望以及家長對自己參與子女學業的角色建構對家長參與子女學業的影響。此外，基於家長社會化的互動模型，探討了孩子的學業成績對家長參與的影響。研究目的三則探討了家長參與對子女學業和情緒發展的影響，主要關注了家長參與對子女的學習動機、成績以及生活滿意度。 / 323名7年級學生及其家長參加了本次研究。調查分兩次進行，間隔六個月。家長只參加第一次調查，家長報告他們參與子女學業程度以及家長的信念。小孩則在兩次調查中報告他們家長的參與程度、學習動機以及生活滿意度。 / 結果表明，中國的家長參與包括了十個維度: 教師發起的基於學校的參與、輔導功課、認知-智力參與、關於當前學業的社會化、關於未來學習目標的社會化、家長發起的基於學校的參與、提供良好環境、設定家庭規則、課外輔導、強化/懲罰。家長的信念和孩子的學業成績影響家長參與的程度。具體來說，這四種家長的信念對家長參與的不同類型影響不同。孩子的成績正向預測了半年後孩子報告的家長的輔導功課、提供良好環境的程度，負向預測了家長的強化/懲罰。橫向調查的結果發現孩子報告的家長參與與孩子的學業相關，但是這種關係因不同類型的家長參與而異。 / 本研究表明了探討不同類型的中國的家長參與子女學業的重要性。本研究也表明家長的信念以及孩子的學業成績對家長參與的程度的影響。 / Wu, Nini. / Thesis Ph.D. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 108-124). / Abstracts also in Chinese; appendix includes Chinese. / Title from PDF title page (viewed on 12, October, 2016). / Wu, Nini. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Glioblastoma multiforme (GBM) is the most aggressive and most common primary brain tumor in adults accounting for 50-60% of primary brain tumors. The prognosis for patients with GBM remains poor and treatment is mainly palliative with a mean survival time of less than one year. Radiotherapy is used extensively in the management of glioblastoma either alone or in combination with surgery and/or chemotherapy. However, this tumor is one of the most resistant tumors to radiotherapy thus limiting the benefit of this form of treatment. <p>Studies have shown that malignant tumors have a high content of glutathione an antioxidant responsible for protecting the cells against damage from free radicals (mainly superoxide, hydroxyl and hydrogen peroxide). It is well established that glutathione, by neutralizing these free radicals plays a major role in radioresistance. Glioblastoma has relatively high levels of glutathione. In this study, by reducing the glutathione content of glioblastoma in a rat model, we were able to investigate the effect of this reduction in enhancing the effect of radiotherapy as a form of treatment for glioblastoma multiforme in a rat model. <p>By injecting L-Buthionine-SR-Sulfoximine (BSO) in to the tumor tissue, the glutathione content of the tumor was reduced by about 70% of its initial value. When administered into the tumors 2 hours prior to radiotherapy the animals so treated had a significantly longer median survival time compared with animals that received radiotherapy alone.