RESUMEN
A high-yielding method for the direct thiocyanation of BODIPY dyes is described. In 1,3-dimethyl BODIPYs, the thiocyanato group adds at position 2, whereas the insertion occurs at position 5 in 3-amino BODIPYs. The transformation of the thiocyanato group enables the synthesis of thioalkylated BODIPYs. 2-Thioalkylated BODIPYs and 3-thiocyanato-5-piperidino BODIPYs exhibit interesting spectroscopical features. Hence, the described synthetic methodology can be used for the photophysical tuning of BODIPY dyes.
Asunto(s)
Compuestos de Boro/química , Colorantes Fluorescentes/síntesis química , Tiocianatos/química , Alquilación , Compuestos de Boro/síntesis química , Cristalografía por Rayos X , Colorantes Fluorescentes/química , Tiocianatos/síntesis químicaRESUMEN
1,4-Naphthoquinone derivatives are known to have relevant activities against several parasites. Among the treatment options for malaria, atovaquone, a 1,4-naphthoquinone derivative, is widely applied in the treatment and prophylaxis of such disease. Based on the structure simplification of atovaquone, we designed and synthesized four novel naphthoquinoidal derivatives. The compounds were obtained by the underexplored epoxide-opening reaction of 1,4-naphthoquinone using aniline derivatives as nucleophiles. The antiplasmodial activity of the synthesized compounds was performed in vivo using Peter's 4days suppression test. Significant parasitemia reduction and increased survival were observed for some of the compounds.
Asunto(s)
Antimaláricos/síntesis química , Antimaláricos/farmacología , Compuestos Epoxi/química , Naftoquinonas/síntesis química , Naftoquinonas/farmacología , Plasmodium falciparum/efectos de los fármacos , Animales , Antimaláricos/química , Malaria/tratamiento farmacológico , Ratones , Estructura Molecular , Naftoquinonas/química , Análisis de SupervivenciaRESUMEN
In the present study, we aimed to evaluate estrogen receptor ER-alpha status in 61 breast cancer cases using Sp1 and 1D5 monoclonal antibodies. Tissue array platforms were generated containing samples of breast cancer and positive controls that were assayed by immunohistochemistry applying monoclonal primary antibodies anti-ER alpha, SP1 and 1D5. We noted a high concordance rate (96.7%) between the referred antibodies. Moreover, we calculated the Kappa factor (0.921), indicating that 1D5 and SP1 provided overlapping ERα expression results. Indeed, we observed controversial results only in 2 samples studied, which were ER-negative when stained with 1D5 and ER-positive when assessed with SP1. Total concordance of PS was obtained (Pearson and intraclass CF, 0.7351 and 0.6193, respectively). However, concordance between the antibodies seems to be more accurate in higher PS values. An excellent IS correlation between antibodies was observed throughout the population (Spearman's CF, ρ=0.9150). Following the Allred score, 17 out of 42 positive BC samples diverged, with 1D5 always pointing to weaker staining than SP1. When calculating Spearman's CF of Total Score (TS) within the population, an excellent correlation between both the antibodies (ρ=0.9238) was noted. Nonetheless, the results were less concordant among the BC-positive cases (ρ=0.7743). Indeed, 20 samples were differentially classified using the antibodies (only 3 had higher TS with 1D5). Considering the mean TS of all samples or of invasive ductal carcinoma, SP1 provided higher scores than 1D5 (p<0.05). We recommend the use of the anti-ER RMAb SP1 due to the high probability that the BC ERα status can be determined accurately as the reagent provides higher IS. Therefore, the A-score was higher than the MMAb 1D5. Ultimately, higher IS and A-score decrease the possibility of ERα status misinterpretation and, consequently, inappropriate BC treatment that would compromise the patient's quality of life and overall survival. We recommend the use of anti-ER RMAb SP1 due to the high probability that the BC ER status can be determined accurately as the reagent provides higher IS, therefore higher A-score, than the MMAb 1D5.
Asunto(s)
Adenocarcinoma/diagnóstico , Anticuerpos Monoclonales , Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/diagnóstico , Receptor alfa de Estrógeno/inmunología , Femenino , Humanos , Inmunohistoquímica/métodos , Reproducibilidad de los Resultados , Análisis de Matrices TisularesRESUMEN
The aim of this work was to study the estrogen receptor alpha (ERS1) PvuII and XbaI gene polymorphisms prevalence in randomly selected women population from Rio de Janeiro and Espírito Santo states in Brazil by polymerase chain reaction restriction fragment lengths polymorphism (PCR_RFLP) methodology. It was shown that Rio de Janeiro women exhibited a significantly different prevalence of XbaI polymorphism comparing to Espirito Santo women. Nonetheless, similar prevalence of PvuII polymorphism was found in both women´s populations. Moreover, a strong linkage disequilibrium was observed between these SNPs reinforcing the hypothesis of differential pattern of inheritance observed on such populations.
RESUMEN
OBJECTIVE: To evaluate the association of -397T>C and -351A>G single nucleotide polymorphisms (SNPs) - also called PvuII and XbaI, respectively - located on estrogen receptor alpha (ERS1) gene with age at menarche, menopause onset, fertility and miscarriage in a population of post-menopausal women. STUDY DESIGN: Cross-sectional study with 273 healthy, high miscegenated, post-menopausal women (mean age of 63.1±9.7 years old). Subjects were genotyped for PvuII and XbaI SNPs by PCR-RFLP and confirmed by automatic sequencing. Reproduction informations (age at menarche, age at menopause, number of pregnancies, fertility rate and miscarriages) were obtained by retrospective study using a questionnaire. RESULT(S): Age at menarche, menopause onset, number of pregnancies, total fertility rate, and parity did not seem to be influenced by any of the studied genotypes (chi-square, p>0.05). However, women carrying the xx genotype showed a 44% higher chance of miscarriage, whereas this value did not trespass 16% for any other genotype analyzed. It has been also observed a higher occurrence of miscarriage in association with combined xxpp genotype of ERS1 gene (chi-square, p<0.01). CONCLUSION(S): The present data indicate that the studied SNPs on ERS1 gene do not influence the menstrual cycle timing and parity but there is a strong relationship between the xx ERS1 SNP genotype and the incidence of miscarriage in the post-menopausal population analyzed.
Asunto(s)
Aborto Espontáneo/genética , Receptor alfa de Estrógeno/genética , Polimorfismo de Nucleótido Simple , Factores de Edad , Anciano , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Fertilidad/genética , Genotipo , Humanos , Menarquia/genética , Menopausia/genética , Persona de Mediana Edad , Paridad/genética , Posmenopausia , EmbarazoRESUMEN
Advances in our understanding of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T(Regs)) enabled the characterization of their activities in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory diseases. Ironically, an effective action of these cells during tumor development can limit beneficial responses by suppressing immunity and limiting antitumor resistance, whereas one of the main functions of the immune system is to eliminate malignant cells. During the last years, the immunological role, mechanism of action, and clinical importance of these cells were profoundly characterized and the relationship between this subset of lymphocytes and cancerous cells arises as a key factor that influences tumor development. Recent insights obtained from clinical studies and experimental mouse models expand our perception of the potential role of T(Regs) in cancer treatment. In this review we describe the basic mechanisms of T(Reg) origin and differentiation, their potential role in cancer, as well as the future perspectives concerning the modulation of these cells as a potential approach for anticancer strategies.
Asunto(s)
Antineoplásicos/uso terapéutico , Inmunoterapia , Neoplasias/terapia , Linfocitos T Reguladores , Animales , Antineoplásicos/farmacología , Ensayos Clínicos como Asunto , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Humanos , Lenalidomida , Ratones , Modelos Animales , Agonistas Mieloablativos/farmacología , Agonistas Mieloablativos/uso terapéutico , Neoplasias/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Talidomida/análogos & derivados , Talidomida/farmacología , Talidomida/uso terapéutico , Vidarabina/análogos & derivados , Vidarabina/farmacología , Vidarabina/uso terapéuticoRESUMEN
Inorganic phosphate (Pi) presents a crucial role in cellular metabolism, with the kidney and intestine as the principal regulating organs of the homeostasis of this nutrient. Maintaining phosphate balance results from the activity of different subtype of transporters of sodium-dependent phosphate that use the electrochemical gradient of sodium ions to carry out cotransport. Several diseases have been related to dysfunctions of phosphate cotransporters, including in the area of oncology. A study using the SAGE technique pointed to a possible role of the type IIb sodium-phosphate cotransporter (NaPi-IIb), encoded by the SLC34A2 gene, in ovarian carcinogenesis. More recently, such protein was associated with the development of other carcinomas and some of the components that regulate its function were determined. It is believed that in the future, the analysis of SLC34A2 expression in tumor samples will help in the choice of treatment, evaluation of prognosis and be a possible target for new therapeutic strategies.