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Monocarboxylate transporters (MCTs) in gliomas : expression and exploitation as...

Gonçalves, Vera M.; Honavar, Mrinalini; Pinheiro, Céline; Martinho, Olga; Pires, Manuel Melo; Pinheiro, Célia; Cordeiro, Michelle; Bebiano, Gil

Background. Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in...


RKIP Inhibition in cervical cancer Is associated with higher tumor aggressive b...

Martinho, Olga; Pinto, Filipe; Granja, Sara Costa; Gonçalves, Vera M.; Longatto Filho, Adhemar; Reis, R. M.; Loreto, Celso di; Rosner, Marsha R.

Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial ...


In vitro and in vivo analysis of RTK inhibitor efficacy and identification of i...

Martinho, Olga; Oliveira, Renato Silva; Gonçalves, Vera M.; Clara, Carlos; Almeida, José Reynaldo; Carvalho, André Lopes; Barata, João Taborda

Treatment for glioblastoma consists of radiotherapy and temozolomide-based chemotherapy. However, virtually all patients recur, leading to a fatal outcome. Receptor tyrosine kinase (RTK)-targeted therapy has been the focus of attention in novel treatment options for these patients. Here, we compared the efficacy of imatinib, sunitinib, and cediranib in glioblastoma models. In the present work, the biologic effe...


Loss of WNK2 expression by promoter gene methylation occurs in adult gliomas an...

Moniz, Sónia; Martinho, Olga; Pinto, Filipe; Sousa, Bárbara; Loureiro, Claúdia; Oliveira, Maria José; Moita, Luis Ferreira; Honavar, Mrinalini

The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours. Following experimental depletion in cell lines, WNK2 was further found to control GTP-loading of Rac1, a signalling guanosine triphosphatase involved in cell migration and motility. Here we show that WNK2 promoter methyl...


Protein Kinase WNK2 has a Tumour Suppressor Role in Gliomas

Moniz, Sonia; Martinho, Olga; Pinto, Filipe; Reis, Rui Manuel; Jordan, Peter

Malignant glioblastoma is the most common and lethal adult brain tumour type. Recently, the promoter region of the protein kinaseWNK2 gene was found to be hypermethylated in 29 of 31 infiltrative gliomas and about 5 of 7 meningiomas. We have previously described that theexperimental depletion of WNK2 expression decreases RhoA activity whilst leading to increased Rac1 activity. RhoA/Rac1 activities are important...


Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147)...

Oliveira, Antônio Talvane Torres; Pinheiro, Céline; Filho, A. L.; Brito, Maria José; Martinho, Olga; Matos, Delcio; Carvalho, André Lopes

Antônio Talvane Torres de Oliveira and Céline Pinheiro contributed equally to the study ; Prova tipográfica (uncorrected proof) ; Monocarboxylate transporters (MCTs) have been described to play an important role in cancer, but to date there are no reports on the significance of MCT expression in gastrointestinal stromal tumors (GISTs). The aim of the present work was to assess the value of MCT expression, as ...


Zeolite structures loading with an anticancer compound as drug delivery systems

Amorim, Ricardo; Vilaça, Natália; Martinho, Olga; Reis, R. M.; Sardo, Mariana; Rocha, João; Fonseca, António Manuel; Baltazar, Fátima

The authors are thankful to Dr. A. S. Azevedo for collecting the powder diffraction data. ; Two different structures of zeolites, faujasite (FAU) and Linde type A (LTA), were studied to investigate their suitability for drug delivery systems (DDS). The zeolites in the sodium form (NaY and NaA) were used as hosts for encapsulation of α-cyano-4- hydroxycinnamic acid (CHC). CHC, an experimental anticancer drug, w...


Downregulation of RKIP is associated with poor outcome and malignant progressio...

Martinho, Olga; Granja, Sara Costa; Jaraquemada, Teresa; Caeiro, Cláudia; Gonçalves, Vera M.; Honavar, Mrinalini; Costa, Paulo; Damasceno, Margarida

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis ...


Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gast...

Oliveira, Antônio Talvane Torres; Reis, R. M.; Afonso, Julieta; Martinho, Olga; Matos, Delcio; Carvalho, André Lopes; Vazquez, Vinícius Lima

This study aimed to assess the distribution of VEGF-C and VEGFR-3 expression in gastrointestinal stromal tumours (GISTs), and to analyse the value of lymphatic vessel density (LVD) in a tumour that is believed to preferentially metastasize through blood vessel conduits. A panel of immunohistochemical antibodies was used to evaluate 51 cases of genetically characterised GISTs: VEGF-C, VEGFR-3, D2-40 (for LVD ass...


Prognostic value of MGMT promoter methylation in glioblastoma patients treated ...

Costa, Bruno Marques; Caeiro, Cláudia; Guimarães, Inês; Martinho, Olga; Jaraquemada, Teresa; Augusto, Isabel; Castro, Lígia; Osório, Lígia

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-speci...


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Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia