RESUMO
Intratumoral heterogeneity (ITH) represents an obstacle for cancer diagnosis and treatment, but little is known about its functional role in cancer progression. The A Desintegrin And Metalloproteinase 23 (ADAM23) gene is epigenetically silenced in different types of tumors, and silencing is often associated with advanced disease and metastasis. Here, we show that invasive breast tumors exhibit significant ADAM23-ITH and that this heterogeneity is critical for tumor growth and metastasis. We demonstrate that while loss of ADAM23 expression enhances invasion, it causes a severe proliferative deficiency and is not itself sufficient to trigger metastasis. Rather, we observed that, in ADAM23-heterotypic environments, ADAM23-negative cells promote tumor growth and metastasis by enhancing the proliferation and invasion of adjacent A23-positive cells through the production of LGI4 (Leucine-rich Glioma Inactivated 4) and nitric oxide (NO). Ablation of LGI4 and NO in A23-negative cells significantly attenuates A23-positive cell proliferation and invasion. Our work denotes a driving role of ADAM23-ITH during disease progression, shifting the malignant phenotype from the cellular to the tissue level. Our findings also provide insights for therapeutic intervention, enforcing the need to ascertain ITH to improve cancer diagnosis and therapy.
Assuntos
Proteínas ADAM/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas da Matriz Extracelular/metabolismo , Óxido Nítrico/metabolismo , Proteínas ADAM/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células , Metilação de DNA , Epigênese Genética , Proteínas da Matriz Extracelular/genética , Feminino , Inativação Gênica , Humanos , Metástase Neoplásica , Proteínas do Tecido Nervoso , Carga Tumoral , Microambiente TumoralRESUMO
Avaliou-se o efeito da inclusão de zeólita na dieta de bovinos de corte sobre os parâmetros ruminais, as digestibilidades total e parcial, a produção de nitrogênio, a eficiência microbiana e as características do sangue. Os tratamentos, com base na matéria seca (MS) da dieta, foram: 0; 0,75; 1,5; 2,25 e 3,0% de zeólita. Utilizaram-se cinco bovinos machos mestiços, fistulados no rúmen e abomaso, alimentados com silagem de milho e concentrado, representando 65% de volumoso e 35% de concentrado. O delineamento utilizado foi em quadrado latino 5×5, com cinco períodos de 15 dias. Os animais receberam 15g de dióxido de titânio (TiO2) do terceiro ao 12º dia de cada período. Houve efeito (P<0,05) sobre o consumo diário (kg/dia) de proteína bruta (PB) e efeito (P<0,05) sobre o consumo de MS e de fibra em detergente neutro corrigida para cinza e proteína, expresso em g/kg de peso. A digestibilidade total dos nutrientes digestíveis totais (NDT) foi influenciada pelos tratamentos (P<0,05). A digestibilidade ruminal dos carboidratos não fibrosos (CNF) foi afetada quadraticamente (P<0,05), assim como a intestinal da PB e dos CNF. A ingestão e a excreção fecal de nitrogênio (g/dia) foram influenciadas linearmente (P<0,05) pela inclusão de zeólita. Concluiu-se que a adição de zeólita na dieta, embora tenha aumentado os consumos de MS e de FDN, não melhorou a utilização da ureia em dietas de bovinos de corte.
We evaluated the effect of the inclusion of zeolite in the diet of beef cattle on the ruminal digestibility, total and partial production of nitrogen, microbial efficiency and blood characteristics. Treatments based on the dietary dry matter (DM) were: 0%, 0.75%, 1.5%, 2.25% and 3.0% of zeolite. We used five crossbred steers fistulated in the rumen and abomasum, fed corn silage and concentrate, representing 65% forage and 35% concentrate. The design was a 5x5 latin square with five periods of 15 days. The animals received 15g of titanium dioxide (TiO2) from the third to the 12th day of each period. A significant effect (P<0.05) on the daily consumption (kg/day) of crude protein (CP) was observed (P<0.05) for DM intake and neutral detergent fiber corrected for ash and protein (NDFap) expressed in g/kg. The total digestibility of total digestible nutrients (TDN) was influenced by treatments (P<0.05). Ruminal digestibility of non-fiber carbohydrates (NFC) was affected quadratically (P<0.05) as well as intestinal CP and NFC. Intake and fecal excretion of nitrogen (g/day) were affected linearly (P<0.05) by adding zeolite. It was concluded that the addition of zeolite in the diet, while increasing the intake of DM and NDF, did not improve the use of urea in the diet of beef cattle.
RESUMO
Avaliou-se o efeito da inclusão de zeólita na dieta de bovinos de corte sobre os parâmetros ruminais, as digestibilidades total e parcial, a produção de nitrogênio, a eficiência microbiana e as características do sangue. Os tratamentos, com base na matéria seca (MS) da dieta, foram: 0; 0,75; 1,5; 2,25 e 3,0% de zeólita. Utilizaram-se cinco bovinos machos mestiços, fistulados no rúmen e abomaso, alimentados com silagem de milho e concentrado, representando 65% de volumoso e 35% de concentrado. O delineamento utilizado foi em quadrado latino 5×5, com cinco períodos de 15 dias. Os animais receberam 15g de dióxido de titânio (TiO2) do terceiro ao 12º dia de cada período. Houve efeito (P<0,05) sobre o consumo diário (kg/dia) de proteína bruta (PB) e efeito (P<0,05) sobre o consumo de MS e de fibra em detergente neutro corrigida para cinza e proteína, expresso em g/kg de peso. A digestibilidade total dos nutrientes digestíveis totais (NDT) foi influenciada pelos tratamentos (P<0,05). A digestibilidade ruminal dos carboidratos não fibrosos (CNF) foi afetada quadraticamente (P<0,05), assim como a intestinal da PB e dos CNF. A ingestão e a excreção fecal de nitrogênio (g/dia) foram influenciadas linearmente (P<0,05) pela inclusão de zeólita. Concluiu-se que a adição de zeólita na dieta, embora tenha aumentado os consumos de MS e de FDN, não melhorou a utilização da ureia em dietas de bovinos de corte.(AU)
We evaluated the effect of the inclusion of zeolite in the diet of beef cattle on the ruminal digestibility, total and partial production of nitrogen, microbial efficiency and blood characteristics. Treatments based on the dietary dry matter (DM) were: 0%, 0.75%, 1.5%, 2.25% and 3.0% of zeolite. We used five crossbred steers fistulated in the rumen and abomasum, fed corn silage and concentrate, representing 65% forage and 35% concentrate. The design was a 5x5 latin square with five periods of 15 days. The animals received 15g of titanium dioxide (TiO2) from the third to the 12th day of each period. A significant effect (P<0.05) on the daily consumption (kg/day) of crude protein (CP) was observed (P<0.05) for DM intake and neutral detergent fiber corrected for ash and protein (NDFap) expressed in g/kg. The total digestibility of total digestible nutrients (TDN) was influenced by treatments (P<0.05). Ruminal digestibility of non-fiber carbohydrates (NFC) was affected quadratically (P<0.05) as well as intestinal CP and NFC. Intake and fecal excretion of nitrogen (g/day) were affected linearly (P<0.05) by adding zeolite. It was concluded that the addition of zeolite in the diet, while increasing the intake of DM and NDF, did not improve the use of urea in the diet of beef cattle.(AU)
Assuntos
Animais , Bovinos , Bovinos/crescimento & desenvolvimento , Zeolitas/administração & dosagem , Ureia/metabolismo , Rúmen/metabolismo , Proteínas Alimentares/administração & dosagemRESUMO
O trabalho teve como objetivo avaliar a influência de doses de cinzas em diferentes substratos no enraizamento de estacas de manjericão (Ocimum basilicum). O experimento foi conduzido em área do Núcleo de Capacitação e Pesquisa da Universidade Federal Rural da Amazônia, em Belém. Foi utilizado o delineamento experimental inteiramente casualizado, em esquema fatorial 2 x 5, constituído pelas combinações entre os fatores substratos (casca de arroz carbonizada e casca de castanha triturada) e acréscimo de cinzas (5 mL e 10 mL de cinza de casca de arroz, 5 mL e 10 mL de cinza de casca de castanha e sem cinza) com 4 repetições. Cada unidade experimental foi constituída por 10 estacas, num total de 400 estacas. Foram avaliadas as características percentual de enraizamento de estacas, número e comprimento de raízes. Não houve interações significativas entre os fatores avaliados (substrato e cinzas). Entre as características avaliadas o substrato casca de arroz carbonizada apresentou diferenças apenas no comprimento da raiz e no número de raízes, enquanto as dosagens de cinzas apresentaram diferenças apenas no percentual de enraizamento. O trabalho permitiu concluir que as dosagens de cinzas apresentaram efeito positivo sobre o enraizamento das estacas de manjericão, assim como o substrato a base de casca de arroz carbonizada propiciou melhores condições para o desenvolvimento das raízes. Assim, a casca de arroz é uma alternativa totalmente viável, pois além de apresentar características apropriadas para o enraizamento também possui baixo custo de aquisição, estando ao alcance de muitos produtores.
The study aimed to evaluate the influence of ash doses on different substrates on the stem rooting of basil (Ocimum basilicum). The experiment was conducted in the area of core training and research at the Universidade Federal Rural da Amazônia, in Belém, used a completely randomized design, factorial scheme 2 x 5 consisting of the combinations of the factors substrate (carbonized rice husk and bark brown ground) and increase ash (5 mL and 10 mL of rice husk ash 5 mL and 10 mL of husk ash and brown bark no gray) with four repetitions. Each experimental unit consisted of 10 cuttings, a total of 400 cuttings. Was evaluated the characteristics percentage of rooting, number and length of roots. There was no significant interaction between the factors evaluated (substrate and ash). Among the characteristics evaluated the carbonized rice showed only differences in root length and root number, while the levels of ash showed only differences in rooting percentage. The study revealed that the dosages of ash had a positive effect on rooting of cuttings of basil, as well as the substrate prepared with rice hulls provided the best conditions for root development. Thus, the rice husk is an alternative, as well as presenting features suitable for rooting also has a low cost of acquisition, being within reach of many producers.
Assuntos
Cinzas/métodos , Substratos para Tratamento Biológico/análise , Raízes de Plantas , Ocimum basilicum/crescimento & desenvolvimento , Casca de Planta/efeitos adversosRESUMO
BACKGROUND AND AIMS: Hypertriglyceridemia is an important independent risk factor for coronary artery diseases and is determined by a wide range of factors, both genetic and exogenous. The A5 apolipoprotein, which is associated with the synthesis and removal of triglycerides (TG), is encoded by the APOA5 gene. One of the polymorphisms of this gene that has been the focus of a large number of studies, and which appears to be associated with increased TG, is S19W (rs 3135506). In this study, we examined the influence of this single nucleotide polymorphism (SNP) on TG levels of a sample of southern Brazilians. METHODS AND RESULTS: Samples obtained from 567 people of European descent were genotyped; interactions between this variant and anthropometric variables were analyzed, and the effects of lifestyle, sex, menopause, and variations of the APOE gene were evaluated. We found that the 19W allele is associated with increased TG (p = 0.025) and that this influence was modulated by sex (p = 0.003), menopause (p = 0.022) and the presence of the E*4 allele (p = 0.027). CONCLUSION: Our data showed, for the first time, the importance and magnitude of the influence of the S19W variant in a southern Brazilian population.
Assuntos
Apolipoproteínas A/genética , Apolipoproteínas E/genética , Menopausa , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Adulto , Alelos , Apolipoproteína A-V , Apolipoproteínas A/metabolismo , Apolipoproteínas E/metabolismo , Brasil , Doença da Artéria Coronariana , Feminino , Genótipo , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/genética , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
It is known that complete axillary lymph node dissection for breast cancer treatment causes more frequent sensitive and motor alterations in the homolateral shoulder and upper limb than sentinel lymph node (SLN) biopsy. However, it is not clear how often patients treated by SLN biopsy suffer from shoulder mobility (SM) restriction, as well as its severity and duration. This study was done aiming to evaluate SM in 38 patients with early infiltrating breast cancer treated by SLN biopsy in whom shoulder movements were assessed before surgery and repeated at one, two and three months later. Shoulder-arm mobility was evaluated by goniometry considering flexion, abduction, aduction, extension, internal rotation and external rotation. An abnormal result for each movement was defined by restriction greater than ten degrees compared to preoperative findings. Significant abnormal results for flexion and abduction were found in all of the patients at the first month evaluation. At the third month assessment no women showed any kind of SM impairment. The average restriction evolution for each of the parameters is presented. It is concluded that there is frequently a slight and transient SM limitation in patients undergoing SLN biopsy. Early postoperative physiotherapeutical assistance should thus be advisable to relieve and shorten disability symptomatology.
Assuntos
Amplitude de Movimento Articular , Biópsia de Linfonodo Sentinela/efeitos adversos , Articulação do Ombro/fisiopatologia , Adulto , Idoso , Artrometria Articular , Axila , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Pessoa de Meia-IdadeRESUMO
RESUMO O grau de radiosensibilidade de um embrião vegetal depende da espécie, do estágio de desenvolvimento deste embrião durante a irradiação, da dose empregada e do critério usado para medir o efeito biológico. Um dos critérios mais comuns utilizado para avaliar a radiosensibilidade de sementes é medir a altura da planta em um tempo determinado após a germinação. A dose de radiação necessária para provocar uma redução de 50% na altura média da população estudada chama-se GR50 (growth reduction to 50%) e a dose que mata 50% da população em estudo é chamada de dose letal para 50% da população ou LD50 (lethal dose to 50%). O objetivo deste trabalho foi estudar quantitativamente a sensibilidade da soja à radiação gama através do GR50 e LD50. As sementes variedade IAC 12 provenientes do Instituto Agronômico, Campinas, SP, foram irradiadas em uma fonte de 60Co tipo gammacell modelo 220 no CENA com taxa de dose de 1,481 kGy/h. As doses em kGy foram as seguintes: 0,0 (controle), 0,10, 0,20, 0,30, 0,40 e 0,50. Concluiu-se que o GR50 da soja ocorre em 0,30 ± 0,04 kGy. Não foi possível determinar o LD50 para a faixa de doses utilizadas neste experimento.
ABSTRACT The degree of radiosensitivity depends mostly on the species, the stage of the embryo at irradiation, the doses employed and the criteria used to measure the effect. One of the most common criteria to evaluate radiosensitivity in seeds is to measure the average plant height at a determined time after germination. The radiation dose value that causes a 50% growth reduction of a population is called GR50. The goal of this research was to study soybean radiosensitivity from a quantitative point of view. Soybena seeds from Instituto Agronômico, Campinas, SP, were irradiated in a 60Co gamma source type 220 excell from MDS Nordion with dose rate of 1.48 kGy / h in CENA. Applied doses in kGy unit was follows: 0.0, 0.10, 0.20, 0.30, 0.40 and 0.50. It was concluded that the GR50 of soybeans is 0.30 ± 0.04 kGy. It was not possible to determine the LD50 for the dose range employed in this experiment.
Assuntos
Árvores , Agricultura , Brasil , Conservação dos Recursos Naturais , Indústrias , Mudança SocialRESUMO
Venoms from five species of Micrurus (coral snakes) from Brazil (Amazonas State) were tested for the following effects: edematogenic, myotoxic, coagulant, hemorrhagic and phospholipase A2 (PLA2) detection. None of the venoms tested presented coagulant activity. The presence of PLA2 was detected by ELISA in the venoms of M. spixii, M. averyi and M. lemniscatus. The myotoxicity was estimated by the increase in the serum creatine kinase level and by histological analysis. All venoms, except that from M. surinamensis, induced intense edematogenic and myotoxic effects. The venom of M. averyi showed hemorrhagic activity which was confirmed by histopathological analysis. This is the first evidence of such an effect by coral snake venom.
Assuntos
Venenos Elapídicos/toxicidade , Elapidae , Músculos/efeitos dos fármacos , Músculos/patologia , Animais , Creatina Quinase/sangue , Edema/induzido quimicamente , Venenos Elapídicos/análise , Ensaio de Imunoadsorção Enzimática , Hemorragia/induzido quimicamente , Injeções Intramusculares , Camundongos , Fosfolipases A/análise , Fosfolipases A2 , Especificidade da EspécieRESUMO
CA 15.3, a new tumor marker, is a glycoprotein antigen produced in greater amounts by breast tumor cells. It can be quantitatively detected, circulating in human serum or plasma, using an immunoradiometric assay with monoclonal antibodies. In order to evaluate the usefulness of the method and to determine the cut-off for metastatic disease, the CA 15.3 levels were determined in 78 patients (5 patients with breast fibroadenoma and 73 patients with breast cancer). The conclusions of the study are that the CA 15.3 is a useful parameter in the management of patients in different stages of the disease: levels above 36 U/ml are suggestive of metastasis, and above 86 U/ml are indicative of them. On the other hand, CA 15.3 does not seem to be helpful in the pre-operative differential diagnosis of breast lumps.
Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Neoplasias da Mama/imunologia , Carcinoma Ductal de Mama/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/secundário , Diagnóstico Diferencial , Feminino , Humanos , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Acute pancreatitis in pregnancy is not a frequent condition: only a few hundred cases have been published in the literature. Its diagnosis can be misguided by clinical manifestations of the pregnancy itself, and by the delay in ordering the required diagnostic tests. These facts may contribute to the serious prognosis of this disease, which in the past had a mortality of up to 20%. The treatment recommended is conservative. A surgical intervention in the event of biliary lithiasis is best to be postponed till after delivery. Parenteral alimentation can be helpful because of its effects in the promotion of pancreatic rest with simultaneous improvement of the nutritional conditions of the mother and the fetus.
Assuntos
Pancreatite/terapia , Nutrição Parenteral , Complicações Infecciosas na Gravidez/terapia , Doença Aguda , Adjuvantes Imunológicos/administração & dosagem , Adulto , Feminino , Humanos , GravidezRESUMO
E apresentado um caso de tumor misto da pele. Foi realizada uma breve revisao da literatura, e os aspectos clinicos e histologicos do caso sao descritos e comparados aos da literatura mundial