RESUMO
INTRODUCTION AND AIMS: Mucin 1 (MUC1) is a transmembrane glycoprotein that is overexpressed in many tumor types, including breast, pancreatic, and ovarian cancer. The aim of this study was to create a construct containing sodium-iodide symporter (NIS) under the control of the 0.8-kb MUC1 promoter to infect pancreatic cancer cells both in vitro and in vivo, to investigate the potential for radioiodide imaging and ablation of this disease. METHODOLOGY: We amplified the 797-bp MUC1 promoter by two-step nested PCR. Subsequently, a replication-deficient adenoviral construct was created containing the MUC1 promoter followed by the human NIS gene. Iodide uptake assays and immunofluorescence were used to confirm NIS expression and function. Pancreatic cancer xenografts in mice were infected with Ad/MUC1/NIS and then imaged and treated using radioiodide. RESULTS: A 23- and 15.5-fold increase in iodide uptake was observed in Ad/MUC1/NIS-infected MUC1-positive Capan-2 and SW1990 cells with no significant increase observed in MUC1-negative Hela cells or in cells infected with the control virus. The in vivo study showed a clear image of Ad/MUC1/NIS-infected tumor xenografts using (125)I. Administration of a therapeutic dose of (131)I resulted in a regression in size to 76 +/- 15% of their original volume, whereas control tumors continued to increase in size to >200% of their original volume. CONCLUSIONS: These results show that the 0.8-kb MUC1 promoter was successfully used to drive human NIS-targeted expression in pancreatic cancer cells, and Ad/MUC1/NIS-mediated radiotherapy can make pancreatic cancer xenografts in mice shrinking. This could potentially have applications for both imaging and therapy in other MUC1-positive tumors.
Assuntos
Iodetos/metabolismo , Mucina-1/genética , Neoplasias Pancreáticas/radioterapia , Regiões Promotoras Genéticas/fisiologia , Simportadores/biossíntese , Animais , Sequência de Bases , Linhagem Celular Tumoral , Feminino , Imunofluorescência , Células HeLa , Humanos , Radioisótopos do Iodo/uso terapêutico , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Neoplasias Pancreáticas/metabolismo , Simportadores/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To assess the recovery effect of panaxatriol (PT) on myeloid hemopoiesis in radiation injured mice, and analyze the underlying mechanism. METHODS: This study was carried out in the Animal Center of Shandong University, Jinan, China, during March to September 2006. Forty-five inbred albino mice were separated randomly into 3 groups: control group, radiation group, and radiation + PT group (200 mg/kg/d, 3 weeks). Peripheral blood cells were detected by globuli meter, CD34+ cells in bone marrow were detected by flow cytometry, and the protein expression of granulocyte-macrophage colony stimulating factor (GM-CSF) was detected by immunocytochemistry. RESULTS: The numbers of peripheral blood cells and bone marrow CD34+ cells, and the expression of GM-CSF in the radiation group were lower than in the control group. After treatment with PT, the numbers of peripheral blood cells and CD34+ cells, and the expression of GM-CSF increased significantly. CONCLUSION: Panaxatriol can relieve myelosuppression induced by radiation injury. The abilities of regulating the expression of hemopoietic growth factor GM-CSF and promoting the maturation of bone marrow cells may be responsible for some of these beneficial effects.
Assuntos
Ginsenosídeos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Hematopoese/efeitos dos fármacos , Lesões por Radiação/sangue , Triterpenos/farmacologia , Animais , Contagem de Células Sanguíneas , Células da Medula Óssea/metabolismo , Hemoglobinas/metabolismo , CamundongosRESUMO
Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% less than 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation.
Assuntos
Neoplasias Induzidas por Radiação/epidemiologia , Nêutrons , Exposição Ocupacional , Saúde Ocupacional , Petróleo , China , HumanosRESUMO
AIM: To identify the cathepsins in adult worms of Schistosoma japonicum and their proteolytic activities. METHODS: The vomitus from adult worms of S. japonicum was collected. The proteolytic activity of cathepsins in the vomitus was identified and measured using synthetic substrates with arginyl bonds. RESULTS: Specific synthetic subtracts Z-Arg-Arg-AMC (for cathepsin B) and Z-Phe-Arg-AMC (for cathepsin B and L) were degraded by the vomitus. An inhibitor, Z-Phe-PheCHN2 for cathepsin L, inhibited partially the activity of the vomitus to degrade Z-Phe-Arg-AMC. The optimal pH for cathepsin B/L is 5.0-5.5. CONCLUSION: The vomitus of S. japonicum has cathepsin B- and L-like activity.
Assuntos
Catepsinas/análise , Schistosoma japonicum/enzimologia , AnimaisRESUMO
Obesity is a growing threat to women of childbearing age. Increased maternal weight or excessive weight gain in pregnancy is associated with adverse pregnancy outcomes. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on a number of clinical outcomes. There is no consensus amongst the trialists on the core outcomes that need to be reported to inform the clinical care of pregnant women. The aim of this systematic review is to evaluate variation in the type and quality of outcomes reported in systematic reviews and randomised controlled trials on diet and lifestyle interventions on maternal and fetal outcomes. We will assess the correlation between the type of outcome, the quality of the studies and journal impact factor. We searched the major databases from the inception to October 2013 without language restrictions. We used current recommendations for quality of outcome reporting using a 6-point scale. The quality assessment of systematic reviews and RCTs was performed using the AMSTAR and Jadad scoring systems. Additionally we obtained journals' impact factor in the year of publication. We calculated Spearman rank coefficient to assess the correlation between the type of outcome, and study quality. An overview of outcome reporting will show the current attitude of the researchers towards outcomes of importance when conducting trials on diet and lifestyle management in pregnancy. If our abstract is accepted, we will provide the details of the results.
Assuntos
Isquemia Encefálica/metabolismo , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/biossíntese , Selectinas/biossíntese , Animais , Isquemia Encefálica/complicações , Moléculas de Adesão Celular/biossíntese , Humanos , Inflamação/etiologia , Integrinas/biossíntese , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
The egg of the ascidian Ciona Intestinalis was divided 20 min after fertilization into two fragments, one nucleated and the other non-nucleated. Nucleus of ectodermal, mesodermal, or endodermal cell, taken from gastrula or tail-bud embryo was transplanted into the non-nucleated fragment. The fragment developed into abnormal or partial embryo, of which the cells or tissues were differentiated mainly according to the regional distribution of presumptive organ-forming substances of the egg cytoplasm that the fragment contained. The result indicated that differentiation of cells in ascidians was principally determined by the components of the mature egg cytoplasm, not by the transplanted nucleus, and the activity of the nucleus was, to some degree, controlled by the surrounding cytoplasm.