RESUMO
OBJECTIVE: To analyze the phenotypic characteristics of LAP(+) CD4(+) T lymphocytes and investigate their molecular mechanisms in colorectal cancer (CRC) microenvironment. METHODS: Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors (HD) were collected to isolate the lymphocytes. The different expressions of CCR7, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP(+) CD4(+) T and LAP(-)CD4(+) T lymphocytes were analyzed by flow cytometry (FCM). RESULTS: The FCM assay detected that the percentage of LAP(+) CD4(+) T cells in peripheral blood of the CRC patients were significantly higher than that of HD [(9.44±3.18)% versus (1.49±1.00)%, P<0.001]. In addition, significantly more LAP(+) CD4(+) T cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [(11.76±3.74)% versus (3.87±1.64)%, P<0.001]. LAP(+) CD4(+) T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP(+) CD4(+) T cells was (3.87±1.12)%, significantly lower than that in the LAP(-)CD4(+) T cells (16.70±2.61)%, (P<0.001); the expression of CTLA-4 in the LAP(+) CD4(+) T cells was (36.36±19.14)%, significantly higher than the (19.60±8.91)% in the LAP(-)CD4(+) T cells (P<0.001); the expression of CCR4 in the LAP(+) CD4(+) T cells was (37.72±11.14)%, significantly higher than the (30.06±9.14)% in the LAP(-)CD4(+) T cells (P<0.001); and the expression of CCR5 in the LAP(+) CD4(+) T cells was (18.86±7.10)%, significantly higher than the (13.92±3.31)% in the LAP(-)CD4(+) T cells (P<0.001). CONCLUSIONS: LAP(+) CD4(+) T cells with low expression of Foxp3 and high expressions of CTLA-4, CCR4 and CCR5 are tend to be enriched and accumulated in the tumor tissue. The unique phenotypic characteristics make these cells a distinct subset of lymphocytes, apparently different from the traditional CD4(+) CD25(+) Treg cells.
Assuntos
Neoplasias Colorretais , Linfócitos T CD4-Positivos , Antígeno CTLA-4 , Citometria de Fluxo , HumanosRESUMO
OBJECTIVE: In this study, we adopted maternal diabetes model on rats, which induced by streptozotocin to explore the metabolism changes of rat adipose tissue during the neonatal period. MATERIALS AND METHODS: The female rats were induced as diabetes models by streptozotocin (STZ), and mated with the normal male rats when they entered into adulthood. The chosen male offspring rats were executed at week 12 and the epididymis and subcutaneous fat pad were obtained. Then the adipose cells were extracted and the foundation level and absorbing of insulin induced 2-deoxyglucose (2DG) were assessed. RESULTS: Compared with normal control group, the body weight, fat pad weight of the epididymis and diameter of lipid cells for maternal diabetes offspring rats all increased. Lipid cells of epididymis and the intake of glucose induced by insulin increased. At the same time, glucose was oxidized to CO2 and increased lipid. However, there was no change in the capacity of in vitro lipid decomposition. Also, GLUT4, insulin receptor (IRß), acetyl coenzyme A (ACC), etc. increased in fat pad of maternal offspring of diabetes. CONCLUSIONS: Maternal diabetes had effect on fat metabolism of offspring; lipid storage capacity increased but the ability of lipid decomposition had no change.
Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Hiperglicemia/metabolismo , Animais , Feminino , Glucose/metabolismo , Metabolismo dos Lipídeos , Masculino , Gravidez , Ratos , EstreptozocinaRESUMO
Ten esters of cephalotaxine with amino acids possessing widely different structural features have been synthesized and tested for antitumor activity. Preliminary data showed that compound 6 is the most active one. However, it is still less potent than harringtonine. Other synthetic esters possess varying activities at 10 micrograms/ml. Preliminary structure activity relationship of these esters was discussed.
Assuntos
Harringtoninas/síntese química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Harringtoninas/química , Harringtoninas/farmacologia , Mepesuccinato de Omacetaxina , Humanos , Leucemia Promielocítica Aguda/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
We examined the effects of feeding a fructose, sucrose or reference diet during gestation and lactation on blood substrate levels and insulin sensitivity in rat adipose tissue. Female rats were fed either 50% fructose or 50% sucrose purified diets or a nonpurified diet ad libitum during gestation and lactation. Fasting blood samples were taken on d 10 of gestation and one oral glucose tolerance test was conducted on d 19 of gestation, with a second test performed on the day of weaning. All dams were killed 2 d after weaning. During gestation, fructose feeding induced hyperglycemia and hypertriglyceridemia in early pregnancy (d 10) relative to sucrose-fed rats, and hypotriglyceridemia in late pregnancy (d 19) as compared with the group fed the reference diet. Compared with the reference group, sucrose feeding also caused hypotriglyceridemia during late pregnancy. Pups delivered to fructose-fed dams were hyperglycemic at birth. In comparison with the reference group, fructose-fed dams were hypoglycemic, whereas sucrose-fed dams were hypertriglyceridemic at weaning. There was no difference in each of the two oral glucose tolerance test responses between the three groups after adjusting for the baseline difference in glucose levels. However, lipid synthesis in isolated fat cells in response to insulin stimulation was significantly lower in fructose-fed and sucrose-fed rats relative to the reference group.
Assuntos
Frutose/farmacologia , Sacarose/farmacologia , Administração Oral , Animais , Animais Recém-Nascidos/metabolismo , Glicemia , Peso Corporal , Dieta , Feminino , Frutose/administração & dosagem , Lactação/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Troca Materno-Fetal , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Genomic in situ hybridization (GISH) offers a convenient and effective method for cytological detection, but can not determine the identity of the chromosomes involved. We integrated C-banding with GISH to identify Haynaldia villosa chromosomes in a wheat background. All chromosomes of H. villosa showed C-bands, either in telomeric regions or in both telomeric and centromeric regions, which allowed unequivocal identification of each H. villosa chromosome. The seven pairs of H. villosa chromosomes were differentiated as 1-7 according to their characteristic C-bands. Using a sequential C-banding and GISH technique, we have analyzed somatic cells of F3 plants from the amphiploid Triticum aestivum-H. villosa x 'Yangmai 158' hybrids. Three plants (94009/5-4,94009/5-8 and 94009/5-9) were shown to contain H. villosa chromosome(s). 94009/5-4 (2n = 45) had three H. villosa chromosomes (2, 3 and 4); 94009/5-8 (2n = 45) possessed one chromosome 4 and a pair of chromosome 5, and 94009/5-9 (2n = 43) was found to have one chromosome 6 of H. villosa. The combination of GISH with C-banding described here provides a direct comparison of the cytological and molecular landmarks. Such a technique is particularly useful for identifying and localizing alien chromatin and DNA sequences in plants.