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Soares Mayara Sandrielly Pereira Viau Cassiana Macagnan Saffi Jenifer Costa Marcelo Zanusso da Silva Tatiane Morgana Oliveira Pathise Souto Azambuja Juliana Hofstatter Barschak Alethéa Gatto Braganhol Elizandra S Wyse Angela T Spanevello Roselia Maria Stefanello Francieli Moro 《Metabolic brain disease》2017,32(5):1693-1703
Metabolic Brain Disease - High plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO) may occur in several genetic abnormalities. Patients with hypermethioninemia... 相似文献
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Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model
Andressa Bernardi Elizandra Braganhol Eliézer Jäger Fabrício Figueiró Maria Isabel Edelweiss Adriana R. Pohlmann Sílvia S. Guterres Ana M.O. Battastini 《Cancer letters》2009
Multimodal combinations of target agents with radiation and chemotherapy may enhance cancer treatment efficacy; however, despite these treatments, gliomas recur early due to their highly proliferative, infiltrative and invasive behaviors. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted intensive interest in recent years since they may provide a sustained, controlled and targeted delivery. In the present study, we investigated the effect of indomethacin-loaded nanocapsules in an experimental glioma model. The rats treated with indomethacin-loaded nanocapsules demonstrated a significant reduction in tumor size and half of these animals presented just cells with characteristics of a residual tumor, as shown by immunostaining for nestin. Pathological analyses showed that the treated gliomas presented a significant reduction in the mitotic index and other histological characteristics that indicate a less invasive/proliferative tumor. An important finding of the present study is that indomethacin carried by polymeric nanocapsules achieved higher intracerebral drug concentrations than those of indomethacin in solution. Furthermore, indomethacin achieved a greater concentration in the hemisphere where the glioma was implanted, compared with the contralateral healthy hemisphere. Indomethacin-loaded nanocapsule treatment did not cause characteristics of toxicity and increased the survival of animals. Thus, our results show that polymeric nanocapsules are able to increase the intratumoral bioavailability of indomethacin and reduce the growth of implanted gliomas. Data suggest that indomethacin-loaded nanocapsules could offer new and potentially highly effective strategies for the treatment of malignant gliomas. 相似文献
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Marianne Schrader de Oliveira Giovana Cechim Elisandra Braganhol Daniel Garcia Santos Luise Meurer Cláudio Galvão de Castro Jr. Algemir Lunardi Brunetto Gilberto Schwartsmann Ana Maria Oliveira Battastini Guido Lenz Rafael Roesler 《Journal of neuro-oncology》2009,93(2):203-201
Malignant gliomas have a dismal prognosis despite multi-modality treatments like neurosurgical resection, radiation therapy
and chemotherapy. Evidence has indicated that gastrin-releasing peptide (GRP) and its receptor (GRPR) play a role in the development
of a variety of cancers including gliomas. In the present study, we investigated the effects of RC-3095, a selective GRPR
antagonist, alone or in combination with temozolomide (TMZ), a DNA alkylating agent, in in vitro and in vivo experimental
rat C6 glioma models. Cellular proliferation was significantly reduced by all treatments with the combined administration
of TMZ and RC-3095 being the most effective treatment. In in vivo experiments, the control group displayed the largest tumors
(52 ± 15.5 mm3), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 ± 9.7 mm3). The combined therapy produced further reduction in tumor size (10 ± 7.5 mm3). Our results show that the combination of RC-3095 with TMZ produced an important reduction in in vitro and in vivo glioma
growth therefore making RC-3095 a candidate drug to potentiate the effects of the DNA alkylating agent TMZ in the treatment
of glioma.
An erratum to this article can be found at 相似文献
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Feijó Grace dos Santos Jantsch Jeferson Correia Lidia Luz Eller Sarah Furtado-Filho Orlando Vieira Giovenardi Márcia Porawski Marilene Braganhol Elizandra Guedes Renata Padilha 《Metabolic brain disease》2022,37(6):1875-1886
Metabolic Brain Disease - The excessive production of pro-inflammatory mediators, characteristic of obesity, leads to neuroinflammation. Zinc (Zn) and the branched-chain amino acids (BCAA) are... 相似文献
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Zanotto-Filho A Braganhol E Schröder R de Souza LH Dalmolin RJ Pasquali MA Gelain DP Battastini AM Moreira JC 《Biochemical pharmacology》2011,(3):753-424
Identification of novel target pathways in glioblastoma (GBM) remains critical due to poor prognosis, inefficient therapies and recurrence associated with these tumors. In this work, we evaluated the role of nuclear-factor-kappa-B (NFκB) in the growth of GBM cells, and the potential of NFκB inhibitors as antiglioma agents. NFκB pathway was found overstimulated in GBM cell lines and in tumor specimens compared to normal astrocytes and healthy brain tissues, respectively. Treatment of a panel of established GBM cell lines (U138MG, U87, U373 and C6) with pharmacological NFκB inhibitors (BAY117082, parthenolide, MG132, curcumin and arsenic trioxide) and NFκB-p65 siRNA markedly decreased the viability of GBMs as compared to inhibitors of other signaling pathways such as MAPKs (ERK, JNK and p38), PKC, EGFR and PI3K/Akt. In addition, NFκB inhibitors presented a low toxicity to normal astrocytes, indicating selectivity to cancerous cells. In GBMs, mitochondrial dysfunction (membrane depolarization, bcl-xL downregulation and cytochrome c release) and arrest in the G2/M phase were observed at the early steps of NFκB inhibitors treatment. These events preceded sub-G1 detection, apoptotic body formation and caspase-3 activation. Also, NFκB was found overstimulated in cisplatin-resistant C6 cells, and treatment of GBMs with NFκB inhibitors overcame cisplatin resistance besides potentiating the effects of the chemotherapeutics, cisplatin and doxorubicin. These findings support NFκB as a potential target to cell death induction in GBMs, and that the NFκB inhibitors may be considered for in vivo testing on animal models and possibly on GBM therapy. 相似文献
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Elizandra Braganhol Fernanda B. Morrone ressa Bernardi Daiane Huppes Luise Meurer Maria Isabel A. Edelweiss Guido Lenz Márcia R. Wink Simon C. Robson Ana Maria O. Battastini 《Cancer science》2009,100(8):1434-1442
The ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are a family of ectoenzymes that hydrolyze extracellular nucleotides, thereby modulating purinergic signaling. Gliomas have low expression of all E-NTPDases, particularly NTPDase2, when compared to astrocytes in culture. Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic, does not evoke cytotoxic action on the majority of glioma cultures. We have previously shown that the co-injection of apyrase with gliomas decreases glioma progression. Here, we tested whether selective re-establishment of NTPDase2 expression would affect glioma growth. NTPDase2 overexpression in C6 glioma cells had no effect on in vitro proliferation but dramatically increased tumor growth and malignant characteristics in vivo . Additionally, a sizable platelet sequestration in the tumor area and an increase in CD31 or platelet/endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial growth factor and OX-42 immunostaining were observed in C6-Enhanced Yellow Fluorescent Protein (EYFP)/NTPDase2-derived gliomas when compared to controls. Treatment with clopidogrel, a P2Y12 antagonist with anti-platelet properties, decreased these parameters to control levels. These data suggest that the ADP derived from NTPDase2 activity stimulates platelet migration to the tumor area and that NTPDase2, by regulating angiogenesis and inflammation, seems to play an important role in tumor progression. In conclusion, our results point to the involvement of purinergic signaling in glioma progression. ( Cancer Sci 2009) 相似文献
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Braganhol E Zamin LL Canedo AD Horn F Tamajusuku AS Wink MR Salbego C Battastini AM 《Anti-cancer drugs》2006,17(6):663-671
Recent epidemiological and dietary intervention studies in animals and humans have suggested that diet-derived flavonoids, in particular quercetin, may play a beneficial role by preventing or inhibiting tumorigenesis. The aim of this study was to evaluate whether quercetin may act differently on cancer and normal neuronal tissue. In order to investigate this, the U138MG human glioma cell line and hippocampal organotypic cultures were used. The study showed that quercetin induced in glioma cell cultures results in (a) a decrease in cell proliferation and viability, (b) necrotic and apoptotic cell death, (c) arrest in the G2 checkpoint of the cell cycle, and (d) a decrease of the mitotic index. Furthermore, we demonstrated that while quercetin promotes cancer regression it was able to protect the hippocampal organotypic cultures from ischemic damage. To sum up, our results suggest that quercetin induced growth inhibition and cell death in the U138MG human glioma cell line, while exerting a cytoprotective effect in normal cell cultures. 相似文献
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Joséli Stella Luci Bavaresco Elizandra Braganhol Liliana Rockenbach Patrícia Fernandes Farias Márcia R. Wink Alan A. Azambuja Carlos Henrique Barrios Fernanda Bueno Morrone Ana Maria Oliveira Battastini 《Urologic oncology》2010,28(3):260-267
Bladder cancer is the most prevalent tumor in the genitourinary tract. Nucleotides are important molecules that regulate many pathophysiological functions in the extracellular space. Studies have revealed evidence of a relationship between purinergic signaling and urothelial malignancies. Nucleotide-mediated signaling is controlled by a highly efficient enzymatic cascade, which includes the members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDases), ectonucleotide pyrophosphatase/phosphodiesterase (E-NPPs), ecto-alkaline phosphatases, and ecto-5′-nucleotidase/CD73. In an attempt to identify possible differential expression of ectonucleotidases during bladder cancer progression, a comparative analysis between RT4 (grade 1) and T24 (grade 3) bladder cancer cell lines was performed. In RT4 cells, the hydrolysis of tri- and diphosphate nucleosides was higher than monophosphonucleosides. T24 cells, however, presented the opposite profile, a low level of hydrolysis of tri- and diphosphate nucleosides and a high level of hydrolysis of monophosphates. Phosphodiesterase activity was negligible in both cell lines at physiological pH, indicating that these enzymes are not active under our assay conditions, although they are expressed in both cell lines. The T24 cells expressed NTPDase5 mRNA, while the RT4 cells expressed NTPDase3 and NTPDase5 mRNA. Both cell lines expressed ecto-5′-nucleotidase/CD73 mRNA. The present work describes, for the first time, the differential pattern of ectonucleotidases in the more malignant bladder cancer cells compared with cells derived from an early stage of bladder cancer. Our results open new avenues for research into the physiological roles of this family of enzymes and their possible therapeutic potential in bladder cancer. 相似文献
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Bona Natália P. Pedra Nathalia S. Azambuja Juliana H. Soares Mayara S. P. Spohr Luíza Gelsleichter Nicolly E. de M. Meine Bernardo Sekine Fernanda G. Mendonça Lorenço T. de Oliveira Francine H. Braganhol Elizandra Spanevello Roselia M. da Silveira Elita F. Stefanello Francieli Moro 《Metabolic brain disease》2020,35(2):283-293
Metabolic Brain Disease - Glioblastoma is a devastating tumor affecting the central nervous system with infiltrative capacity, high proliferation rate and chemoresistance. Therefore, it is urgent... 相似文献