RESUMO
Iron (Fe) is an essential microelement for all living organisms playing important roles in several metabolic reactions. Rice (Oryza sativa L.) is commonly cultivated in paddy fields, where Fe goes through a reduction reaction from Fe3+ to Fe2+. Since Fe2+ is more soluble, it can reach toxic levels inside plant cells, constituting an important target for studies. Here we aimed to verify morphological changes of different rice genotypes focusing on deciphering the underlying molecular network induced upon Fe excess treatments with special emphasis on the role of four WRKY transcription factors. The transcriptional response peak of these WRKY transcription factors in rice seedlings occurs at 4 days of exposition to iron excess. OsWRKY55-like, OsWRKY46, OsWRKY64, and OsWRKY113 are up-regulated in BR IRGA 409, an iron-sensitive genotype, while in cultivars Nipponbare (moderately resistant) and EPAGRI 108 (resistant) the expression profiles of these transcription factors show similar behaviors. Here is also shown that some cis-regulatory elements known to be involved in other different stress responses can be linked to conditions of iron excess. Overall, here we support the role of WRKY transcription factors in iron stress tolerance with other important steps toward finding why some rice genotypes are more tolerant than others.
Assuntos
Ferro/metabolismo , Oryza/genética , Fenótipo , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Genoma de Planta , Ferro/toxicidade , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Fatores de Transcrição/metabolismoRESUMO
WHAT IS KNOWN AND OBJECTIVES: Most antineoplastic drugs are highly toxic and have low therapeutic indexes, which can result in drug-related problems. In this context, pharmacist interventions may play an important role in the success of the treatment. The objective of this study was to examine the effects of pharmacist interventions on adult outpatients with cancer using antineoplastic drugs. METHODS: A literature search was performed using PubMed, ISI Web of Science and LILACS databases from January 1990 to April 2016, using MeSH terms or text words related to pharmacist interventions, cancer and outpatient care. Studies published in English, Portuguese or Spanish on the effects of pharmacist interventions in outcome measures in adult outpatients with cancer were included. Two independent authors performed study selection and data extraction with a consensus process. The articles were analysed according to previously established criteria, such as country, study design, setting, population, type of cancer, description of the intervention and control groups, outcomes, main conclusions and study limitations. RESULTS AND DISCUSSION: A total of 874 records were identified, of which 11 satisfied the inclusion criteria. The studies were conducted mainly in the United States and included patients aged >50 years. Most studies had a before-after design. Pharmacist interventions primarily included educating and counselling patients on the management of adverse events. Rates of nausea and vomiting control, medication adherence and patient satisfaction were the most common outcome measures; a significant benefit in these parameters as a result of pharmacist interventions was noted in most studies. WHAT IS NEW AND CONCLUSION: The findings from this systematic review indicate that pharmacist interventions can improve outcome measures in outpatients with cancer. However, the collective quality of the studies was poor and gaps identified indicate that further research is needed to provide more robust results.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Farmacêuticos/organização & administração , Adulto , Assistência Ambulatorial/organização & administração , Humanos , Adesão à Medicação , Avaliação de Resultados em Cuidados de Saúde , Pacientes Ambulatoriais , Satisfação do Paciente , Papel ProfissionalRESUMO
UNLABELLED: In spite of considerable evidence on the regulation of immunity by thyroid hormones, the impact of the thyroid status in tumor immunity is poorly understood. Here, we evaluated the antitumor immune responses evoked in mice with different thyroid status (euthyroid, hyperthyroid, and hypothyroid) that developed solid tumors or metastases after inoculation of syngeneic T lymphoma cells. Hyperthyroid mice showed increased tumor growth along with increased expression of cell cycle regulators compared to hypothyroid and control tumor-bearing mice. However, hypothyroid mice showed a higher frequency of metastases than the other groups. Hyperthyroid mice bearing tumors displayed a lower number of tumor-infiltrating T lymphocytes, lower percentage of functional IFN-γ-producing CD8(+) T cells, and higher percentage of CD19(+) B cells than euthyroid tumor-bearing mice. However, no differences were found in the distribution of lymphocyte subpopulations in tumor-draining lymph nodes (TDLNs) or spleens among different experimental groups. Interestingly, hypothyroid TDLN showed an increased percentage of regulatory T (Treg) cells, while hyperthyroid mice displayed increased number and activity of splenic NK cells, which frequency declined in spleens from hypothyroid mice. Moreover, a decreased number of splenic myeloid-derived suppressor cells (MDSCs) were found in tumor-bearing hyperthyroid mice as compared to hypothyroid or euthyroid mice. Additionally, hyperthyroid mice showed increased cytotoxic activity, which declined in hypothyroid mice. Thus, low levels of intratumoral cytotoxic activity would favor tumor local growth in hyperthyroid mice, while regional and systemic antitumor response may contribute to tumor dissemination in hypothyroid animals. Our results highlight the importance of monitoring the thyroid status in patients with T cell lymphomas. KEY MESSAGES: T cell lymphoma phenotype is paradoxically influenced by thyroid status. Hyperthyroidism favors tumor growth and hypothyroidism rises tumor dissemination. Thyroid status affects the distribution of immune cell types in the tumor milieu. Thyroid status also modifies the nature of local and systemic immune responses.
Assuntos
Imunomodulação , Linfoma de Células T/imunologia , Linfoma de Células T/metabolismo , Doenças da Glândula Tireoide/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Contagem de Linfócitos , Linfoma de Células T/complicações , Linfoma de Células T/patologia , Camundongos , Metástase Neoplásica , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Doenças da Glândula Tireoide/complicações , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/farmacologia , Carga Tumoral , Microambiente Tumoral/imunologiaRESUMO
In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 µg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.
Assuntos
Dextranos/farmacocinética , Compostos Férricos/farmacocinética , Campos Magnéticos , Nanopartículas , Animais , Chlorocebus aethiops , Dextranos/administração & dosagem , Dextranos/toxicidade , Cães , Portadores de Fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Compostos Férricos/administração & dosagem , Compostos Férricos/toxicidade , Técnicas In Vitro , Injeções Intravenosas , Fígado/metabolismo , Pulmão/metabolismo , Células Madin Darby de Rim Canino , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/toxicidade , Neoplasias Mamárias Experimentais/metabolismo , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Polietilenoglicóis , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual , Células VeroRESUMO
BNCT was proposed for the treatment of diffuse, non-resectable tumors in the lung. We performed boron biodistribution studies with 5 administration protocols employing the boron carriers BPA and/or GB-10 in an experimental model of disseminated lung metastases in rats. All 5 protocols were non-toxic and showed preferential tumor boron uptake versus lung. Absolute tumor boron concentration values were therapeutically useful (25-76ppm) for 3 protocols. Dosimetric calculations indicate that BNCT at RA-3 would be potentially therapeutic without exceeding radiotolerance in the lung.
Assuntos
Compostos de Boro/administração & dosagem , Compostos de Boro/farmacocinética , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Fenilalanina/análogos & derivados , Animais , Linhagem Celular Tumoral , Combinação de Medicamentos , Neoplasias Pulmonares/radioterapia , Taxa de Depuração Metabólica , Especificidade de Órgãos , Fenilalanina/administração & dosagem , Fenilalanina/farmacocinética , Dosagem Radioterapêutica , Ratos , Distribuição TecidualRESUMO
We propose a new method for determining the quantity of superparamagnetic iron oxide nanoparticles (Fe3O4, SPIONs) embedded in animal tissue using magnetization measurements. With this method, the smallest detectable quantity of magnetite nanoparticles in a tissue sample is -1 microg. We showed that this method has proved being efficient. In this study, we focused in determining the quantity of SPION confined in lung and liver tissue of mice injected with -13 nm magnetite superparamagnetic nanoparticles. Furthermore, the method allowed us to detect the magnetite nanoparticles present in animal tissues without letting the natural iron ions present in the tissue or blood interfere with the measurements.
Assuntos
Dextranos/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Nanopartículas de Magnetita/química , Nanotecnologia/métodos , Animais , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de ÓrgãosRESUMO
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Once a tumor is established it may attain further characteristics via mutations or hypoxia, which stimulate new blood vessels. Angiogenesis is a hallmark in the pathogenesis of cancer and inflammatory diseases that may predispose to cancer. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage and was previously reported to play a key role in prostate carcinogenesis. To gain insight into the anti-tumoral properties of HO-1, we investigated its capability to modulate PCa associated-angiogenesis. In the present study, we identified in PC3 cells a set of inflammatory and pro-angiogenic genes down-regulated in response to HO-1 overexpression, in particular VEGFA, VEGFC, HIF1α and α5ß1 integrin. Our results indicated that HO-1 counteracts oxidative imbalance reducing ROS levels. An in vivo angiogenic assay showed that intradermal inoculation of PC3 cells stable transfected with HO-1 (PC3HO-1) generated tumours less vascularised than controls, with decreased microvessel density and reduced CD34 and MMP9 positive staining. Interestingly, longer term grown PC3HO-1 xenografts displayed reduced neovascularization with the subsequent down-regulation of VEGFR2 expression. Additionally, HO-1 repressed nuclear factor κB (NF-κB)-mediated transcription from an NF-κB responsive luciferase reporter construct, which strongly suggests that HO-1 may regulate angiogenesis through this pathway. Taken together, these data supports a key role of HO-1 as a modulator of the angiogenic switch in prostate carcinogenesis ascertaining it as a logical target for intervention therapy.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/farmacologia , Neovascularização Patológica/tratamento farmacológico , Neoplasias da Próstata/irrigação sanguínea , Análise de Variância , Animais , Primers do DNA/genética , Heme Oxigenase-1/metabolismo , Técnicas Histológicas , Humanos , Imuno-Histoquímica , Luciferases , Masculino , Camundongos , Camundongos Nus , Neovascularização Patológica/patologia , Plasmídeos/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
The electrochemical treatment of cancer (EChT) consists in the passage of a direct electric current through two or more electrodes inserted locally in the tumor tissue. The extreme pH changes induced have been proposed as the main tumor destruction mechanism. Here, we study ion transport during EChT through a combined modeling methodology: in vivo modeling with BALB/c mice bearing a subcutaneous tumor, in vitro modeling with agar and collagen gels, and in silico modeling using the one-dimensional Nernst-Planck and Poisson equations for ion transport in a four-ion electrolyte. This combined modeling approach reveals that, under EChT modeling, an initial condition with almost neutral pH evolves between electrodes into extreme cathodic alkaline and anodic acidic fronts moving towards each other, leaving the possible existence of a biological pH region between them; towards the periphery, the pH decays to its neutral values. pH front tracking unveils a time scaling close to t(1/2), signature of a diffusion-controlled process. These results could have significant implications in EChT optimal operative conditions and dose planning, in particular, in the way in which the evolving EChT pH region covers the active cancer cells spherical casket.
Assuntos
Modelos Biológicos , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Biologia Computacional , Condutividade Elétrica , Estimulação Elétrica , Eletroquímica , Eletrodos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Transporte de Íons , Camundongos , Camundongos Endogâmicos BALB C , Necrose/terapiaRESUMO
Glypican-3 (GPC3), a proteoglycan bound to the cell membrane through a GPI anchor, is widely expressed in the embryo but down regulated in most adult tissues, with some exceptions as mammary cells. GPC3 is involved in the regulation of cell proliferation and survival in specific cell types. LM3, a murine mammary tumor cell line unable to express GPC3, was stably transfected with the rat GPC3 gene to analyze its role in tumor progression. Upon injection into syngeneic BALB/c mice LM3-GPC3 clones showed less local invasiveness and developed fewer spontaneous and experimental lung metastasis than controls. GPC3-expressing cells were more sensitive to apoptosis induced by serum depletion, exhibited a delay in the first steps of spreading and were less motile than controls. On the other hand, LM3-GPC3 cells were significantly more adherent to FN than control ones. We observed that GPC3 transfectants presented a higher expression of E-cadherin and beta-catenin, molecules whose down regulation has been associated with tumor progression. Exogenous TGF-beta increased MMP-9 activity in both control and GPC3-expressing cells, but did not modulate MMP-2. Contrarily, GPC3 expression prevented the increase of MMP-2 activity induced by IGF-II. Our results suggest that GPC3 has a protective role against mammary cancer progression.