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Abstract: Patients affected by malignant brain tumor present an extremely poor prognosis, notwithstanding improvements in surgery techniques and therapeutic protocols. Late diagnosis and the limitation of conventional therapies are major reasons for this unsolved clinical problem. The blood-brain barrier formed by a complex of endothelial cells, astrocyte and pericytes reduces notably the diffusion of a large number of therapeutic agents. Nanotechnology involves the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer scale. The nanoparticles have emerged as potential vectors for brain delivery able to overcome the difficulties of modern strategies. Nanoparticles drug delivery systems can be, also, used to provide targeted delivery of drugs, improve bioavailability, sustains release of drugs for systemic delivery. Moreover, multi-functionality can be engineered into a single nanoplatform so that it can provide tumor-specific detection, treatment, and follow-up monitoring. In this study we will focus on the blood-brain barrier role and possibilities of its therapeutic overcoming. Recent studies of some kinds of nanoparticles systems in brain tumors treatment are summarized. Keywords: Blood-Brain Barrier,Brain Tumors, Glioma, Glioblastoma Multiforme, Nanoparticles. |
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Abstract: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumour-induced angiogenesis in several types, including melanoma. Bevacizumab, a monoclonal antibody anti-VEGF, could be used as an imaging tool in clinical studies. The aim of this study was to radiolabeled Bevacizumab with 99mTc and evaluate it in vivo imaging properties. Bevacizumab was derivatized with the activated ester succinimidyl-hydrazinonicotinamide hydrochloride (Suc-HYNIC) as a bifunctional coupling agent. A mixture of Tricine/SnCl2.2H2O was added to Bevacizumab-HYNIC and radiolabeled with 99mTcO4-. The radiochemical stability of the radiolabeled sntibody was assessed. Biodistribution studies and SPECT-CT imaging were evaluated in healthy and tumor-bearing C57BL/6J mice at 1, 4 and 24 h (n =5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable over 24 h in solution and serum. In vivo biodistribution studies revealed tumor-to-muscle ratios of 99mTc-HYNIC-Bevacizumab was 9.28, 17.19 and 8.51 at 1, 4 and 24 h p.i. SPECT/CT imaging of tumor-bearing C57BL/6J mice showed tumor selective uptake of 99mTc-HYNIC-Bevacizumab. 99mTc-HYNIC-Bevacizumab could become a potential radiopharmaceutical to evaluate the expression of vascular endothelial growth factor (VEGF) in solid tumors and could be seen as a clinic tool for the screening of solid tumors that might respond to the Bevacizumab chemotherapy. Keywords: Melanoma, Angiogenesis, Bevacizumab, HYNIC, organic synthesis, technetium-99m.Download Full Article |
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Abstract: The Wnt signalling pathway is involved in regulating cellular proliferation and differentiation, and aberrant activation has been described in several cancers including breast. Oestradiol up regulates Wnt pathway gene expression, and thereby activates the Wnt signalling pathway. We used the oestrogen-responsive breast cancer cell line MCF-7 to examine the effects of secreted frizzled related protein 4 (sFRP-4) on oestradiol-induced growth, including gene expression of the Wnt signalling pathway genes Frizzled Receptor, Wnt-10b, and β-catenin. We demonstrate here that sFRP-4 inhibits oestradiol-induced cell growth in the MCF-7 cell line and also down regulates oestradiol-induced expression of selected Wnt signalling genes including β-catenin. We propose that sFRP-4 is a potent inhibitor of the Wnt signalling pathway and may negatively regulate oestradiol-mediated proliferation in human breast cancer cells. Keywords: Breast cancer, sFRP4, Wnt signalling, oestradiol, β-catenin, cellular proliferation, growth inhibition.Download Full Article |
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Abstract: Aims and background: The addition of bevacizumab to preoperative chemotherapy is a common therapeutic practice in patients with colorectal liver metastases. The aim of the present study was to assess the effect of bevacizumab on postoperative complications after liver resection. Methods:A retrospective analysis was performed including patients who underwent liver resection for colorectal liver metastases after receiving chemotherapy with or without bevacizumab in two hospitals. Univariate logistic regression models were used to identify predictors of postoperative morbidity in both groups of patients. Results: A total of 76 patients were analyzed: 22 patients did not receive preoperative chemotherapy (control group), 21 patients received preoperative chemotherapy alone and 33 patients received preoperative chemotherapy in combination with bevacizumab. The median number of chemotherapy cycles received was 4 (range, 1-23) for the chemotherapy group and 7 (range, 2-36) for the chemotherapy plus bevacizumab group Morbidity rate was similar in the three groups of patients considered: 54.5 %, 47.6% and 39.4, respectively. The most common complications were infections and wound complications. The number of preoperative chemotherapy cycles received was the only clinical variable that was significantly correlated with postoperative comorbidity. Conclusions: Our results support the evidence that the addition of bevacizumab to preoperative chemotherapy does not increase the risk of complications following surgery of colorectal liver metastases. Keywords: Colorectal liver metastases, bevacizumab, postoperative complications, preoperative chemotherapy, surgery complications.Download Full Article |
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Abstract: Objectives:Carcinoembryonic antigen (CEA), epidermal growth factor (EGF) and leptin have been reported to be intimately intertwined in lung carcinogenesis.However, few studies have simultaneously examined these proteins in lung cancer and whether a correlation exist among them remains unclear. Here, we compared the levels of CEA, EGF and leptin in non-small-cell lung cancer (NSCLC) patients and controls and evaluated the possible associations among them. Methods:97 patients ranged from 30 to 83 years of age were studied. Serum CEA, EGF and leptin levels were determined following a standard protocol. The relationships between these proteins and clinicopathological factors were evaluated by Wilcoxon rank sum or Kruskal-Wallis H test. Spearman rank-correlation were used to determine the correlations among CEA, EGF and leptin. Co-expression of these proteins in NSCLC tissues was examined by immunofluorescence. Results: Serum CEA and leptin levels in NSCLC patients were significantly higher compared to controls (both P = 0.000), but no statistically significant difference was found for EGF. CEA and EGF were not associated with the tumor-related factors, but leptin was strongly correlated with sex (P = 0.005). Significant correlations among these proteins were found when the patients were categorized into subgroups. Co-expresstion of these proteins was significantly enhanced with lung carcinogenesis. Conclusions:CEA, EGF and leptin may interplay and play vital roles in the pathogenesis of NSCLC. Besides CEA, the leptin levels were also significantly higher in NSCLC patients than in controls. Determination of preoperative leptin levels may prove useful for screening and predicting NSCLC. Keywords: Non-small-cell lung cancer, Carcinoembryonic antigen (CEA), Epidermal growth factor (EGF), Leptin,Immunofluorescence,Correlation.Download Full Article |