Óxido nítrico, GSTP-1 e p53: qual o papel desses biomarcadores nas lesões prostáticas do cão?

Confeccionou-se um microarranjo de tecido (TMA) com 146 amostras de lesões prostáticas caninas. Este continha 17,2% de hiperplasia prostática benigna (HPB), 32,4% de atrofia inflamatória proliferativa (PIA), 2,6% de prostatite, 8,6% de focos de neoplasia intraepitelial prostática (PIN), 29,1% de carcinomas e 9,3% de próstatas normais. Cortes histológicos sequenciais foram feitos e utilizados para reação de imunoistoquímica com os anticorpos primários anti-p-53, anti-NOS-2 e anti-GSTP. Avaliou-se de cada core o escore de células marcadas para cada anticorpo utilizado. Os resultados foram tabulados por grupo diagnóstico e submetidos ao teste Tuckey. Os carcinomas prostáticos do cão e a PIA apresentaram maior número de amostras (41) com mais de 75% das células positivas para NOS-2, demonstrando a influência do estresse oxidativo no desenvolvimento dessas lesões. As próstatas normais e as afecções desta glândula, HPB, PIA, PIN, prostatite e carcinoma, expressaram a proteína GSTP-1, o que conferiu proteção ao tecido prostático canino a danos oxidativos. A proteína p53 estava presente em todas as amostras estudadas, incluindo o tecido prostático normal, porém as lesões prostáticas apresentaram maior número de amostras com escores mais elevados de marcação (escores três e quatro), presente em 95% dos focos de PIA e carcinoma. Concluiu-se que o aumento de expressão de óxido nítrico nas lesões prostáticas no cão e a expressão de GSTP-1 podem ter protegido o tecido prostático canino e que a expressão de p53 foi positiva e uniforme nas próstatas normais e com lesões hiperplásicas e displásicas.

Óxido nítrico, GSTP-1 e P53: qual o papel desses biomarcadores e suas correlações com as afecções prostática no cão?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exposição ao cádmio e/ou à cafeína na puberdade: expressão de marcadores de alterações pré-neoplásicas na próstata de rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Pharmacogenetics of the human glutathione S-transferase P1 gene in the metabolism and therapeutic efficacy of cis-diamminedichloroplatinum

The human GSTP1 gene has been shown, conclusively, to be polymorphic. The three main GSTP1 alleles, GSTP1*A, GSTP1*B, and GSTP1*C, encode proteins which differ in the 3-dimensional structure of their active sites and in their function in phase II metabolism of carcinogens, mutagens, and anticancer agents. Although, it is well established that GSTP1 is over expressed in many human tumors and that the levels of GSTP1 expression correlate directly with tumor resistance to chemotherapy and inversely with patient survival, the significance of the polymorphic GSTP1 gene locus on tumor response to chemotherapy remains unclear. The goal of this project was to define the role and significance of the polymorphic GSTP1 gene locus in GSTP1-based tumor drug resistance and as a determinant of patient response to chemotherapy. The hypothesis to be tested was that the polymorphic GSTP1 gene locus will confer to tumors a differential ability to metabolize cisplatin resulting in a GSTP1 genotype-based sensitivity to cisplatin. The study examined: (a) whether the different GSTP 1 alleles confer different levels of cellular protection against cisplatin-induced cytotoxicity, (b) whether the allelic GSTP1 proteins metabolize cisplatin with different efficiencies, and (c) whether the GSTP1 genotype is a determinant of tumor response to cisplatin therapy. The results demonstrate that the GSTP1 alleles differentially protect tumors against cisplatin-induced apoptosis and clonogenic cell kill in the rank order: GSTP1*C > GSTP1*B > GSTP1*A. The same rank order was observed for the kinetics of GSTP1-catalyzed cisplatin metabolism, both in cell-free and cellular systems, to the rate-limiting monoglutathionyl-platinum metabolite, which was characterized, for the first time, by mass spectral analysis. Finally, this study demonstrates that both GSTP1 genotype and the level of GSTP1 expression significantly contribute to tumor sensitivity to cisplatin treatment. Overall, the results of this project show that the polymorphic GSTP1 gene locus plays a significant role in tumor sensitivity to cisplatin treatment. Furthermore, these studies have contributed to the overall understanding of the significance of the polymorphic GSTP1 gene locus in tumor resistance to cancer chemotherapy and have provided the basis for further investigations into how this can be utilized to optimize and individualize cancer chemotherapy for cancer patients. ^

Vibrational spectroscopy of phthalocyanine and naphthalocyanine in sandwich-type (na)phthalocyaninato and porphyrinato rare earth complexes: Part 14. The infrared and Raman characteristics of phthalocyanine in “pinwheel-like” homoleptic bis[1,8,15,22-tetrakis(3-pentyloxy)phthalocyaninato] rare earth(III) double-decker complexes

The infrared (IR) spectroscopic data and Raman spectroscopic properties for a series of 13 “pinwheel-like” homoleptic bis(phthalocyaninato) rare earth complexes M[Pc(α-OC5H11)4]2 [M = Y and Pr–Lu except Pm; H2Pc(α-OC5H11)4 = 1,8,15,22-tetrakis(3-pentyloxy)phthalocyanine] have been collected and comparatively studied. Both the IR and Raman spectra for M[Pc(α-OC5H11)4]2 are more complicated than those of homoleptic bis(phthalocyaninato) rare earth analogues, namely M(Pc)2 and M[Pc(OC8H17)8]2, but resemble (for IR) or are a bit more complicated (for Raman) than those of heteroleptic counterparts M(Pc)[Pc(α-OC5H11)4], revealing the decreased molecular symmetry of these double-decker compounds, namely S8. Except for the obvious splitting of the isoindole breathing band at 1110–1123 cm−1, the IR spectra of M[Pc(α-OC5H11)4]2 are quite similar to those of corresponding M(Pc)[Pc(α-OC5H11)4] and therefore are similarly assigned. With laser excitation at 633 nm, Raman bands derived from isoindole ring and aza stretchings in the range of 1300–1600 cm−1 are selectively intensified. The IR spectra reveal that the frequencies of pyrrole stretching and pyrrole stretching coupled with the symmetrical CH bending of –CH3 groups are sensitive to the rare earth ionic size, while the Raman technique shows that the bands due to the isoindole stretchings and the coupled pyrrole and aza stretchings are similarly affected. Nevertheless, the phthalocyanine monoanion radical Pc′− IR marker band of bis(phthalocyaninato) complexes involving the same rare earth ion is found to shift to lower energy in the order M(Pc)2 > M(Pc)[Pc(α-OC5H11)4] > M[Pc(α-OC5H11)4]2, revealing the weakened π–π interaction between the two phthalocyanine rings in the same order.

Peripherally η1-Platinated Organometallic Porphyrins as Building Blocks for Multiporphyrin Arrays

The modification of peripherally metalated meso-η1-platiniometalloporphyrins, such as trans-[PtBr(NiDAPP)(PPh3)2] (H2DAPP = 5-phenyl-10,20-bis(3‘,5‘-di-tert-butylphenyl)porphyrin), leads to the analogous platinum(II) nitrato and triflato electrophiles in almost quantitative yields. Self-assembly reactions of these meso-platinioporphyrin tectons with pyridine, 4,4‘-bipyridine, or various meso-4-pyridylporphyrins in chloroform generate new multicomponent organometallic porphyrin arrays containing up to five porphyrin units. These new types of supramolecular arrays are formed exclusively in high yields and are stable in solution or in the solid state for extended periods. They were characterized by multinuclear NMR and UV−visible spectroscopy as well as high-resolution electrospray ionization mass spectrometry.