RESUMO
Regional lymph nodes are important in the generation of tumor-directed immune responses. The relationship between nitric oxide synthase (NOS) expression and the biological behavior of tumor-draining lymph node (TDLNs) cells in vivo was determined using a spontaneously arising BALB/c mammary adenocarcinoma S13. We first demonstrated a reduction of tumor size and tumor-induced angiogenesis by blocking NOS activity in vivo. TDLNs harvested from tumor-bearing mice (TBM) on day 16 after tumor implant, showed enhanced NOS activity and NOS expression compared to control nodes. Identification of the NOS isoforms present in TDLNs resulted in expression of neuronal NOS (nNOS), endothelial NOS (eNOS) and absence of inducible NOS (iNOS). TDLN cells admixed with tumor cells and inoculated into normal mice (Winn assay) induced a reduction of tumor growth although, when inoculated alone, were able to induce the formation of new blood vessels (angiogenesis). Our data indicate that the in vivo antitumor activity of TDLN cells is modulated by a balance between angiogenesis and antitumor effectors. In our model, when trafficking of leukocytes is obviated, the control of tumor growth by TDLN cells can be explained in part by an antitumor activity great enough to exceed the angiogenic component elicited by the same cells, leading to a reduction of tumor size.
Assuntos
Adenocarcinoma/prevenção & controle , Linfonodos/enzimologia , Neoplasias Mamárias Experimentais/prevenção & controle , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/fisiologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/patologia , Animais , Inibidores Enzimáticos/farmacologia , Immunoblotting , Linfonodos/efeitos dos fármacos , Metástase Linfática , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , NG-Nitroarginina Metil Éster/farmacologia , Neovascularização Patológica/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo IIIRESUMO
Oxidative stress is associated with Alzheimer's (DAT) and vascular (VD) dementias, as well as Type II diabetes mellitus (DIAB) and affected by hypoglycemic therapy. The population (n = 122; males = 60; mean age = 72.57 +/- 7.06) consisted of controls (CTR), DAT and VD patients, with (DAT + DIAB, VD + DIAB) and without concomitant DIAB, resulting in six groups where the antioxidant profile was determined: copper-zinc superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and total antioxidant capacity (TRAP). The results were analyzed using a two-way ANOVA design and Bonferroni statistic. The ANOVAs yielded significant differences between groups for all components of the profile: SOD, p = 0.00000006; TBARS, p = 0.0000012; TRAP, p = 0.0000003. The significance level for comparisons between groups was set at alpha = 0.05. The comparisons DIAB vs. CTR, DAT+DIAB vs. DAT, and DIAB demented vs. DIAB non-demented resulted significant for all variables. VD + DIAB vs. VD resulted significant for all variables except TRAP. The antioxidant profiles of DIAB and CTR are different. The differences cannot be directly related with what is observed in dementias. The differences in profiles of demented and non-demented are somewhat hidden when demented patients are affected by a concomitant DIAB condition and/or hypoglycemic treatment, thus conditioning the diagnostic value for dementias of the profiles.