Adriana Umaña

Screening of acetylcholinesterase inhibitors in marine organisms from the Caribbean Sea

Abstract The acetylcholinesterase inhibitory activity of 89 organic extracts from marine organisms was evaluated through a TLC bioautography methodology. Extracts from soft corals (Eunicea and Plexaura) were the most active compared with extracts from sponges. The bioguided chemical study of the most active extract, obtained from Pseudoplexaura porosa, led to the isolation of a diterpene with spectroscopic properties consistent to those published to the cembrane Steylolide. However, further analysis by X-ray diffraction indicated that the compound was the 14-acetoxycrassine (1), correcting the structure reported to the Styelolide. Additionally, the acetylcholinesterase inhibitory activity of fourteen cembranoids (2–15) isolated from soft corals Eunicea knighti and Pseudoplexaura flagellosa was evaluated. Cembranoids 2, 3 and 4 were the most active compounds in the TLC bioassay. Then, the most promising cembranoids, 14-acetoxycrassine (1) and asperdiol (2), were tested quantitatively and they exhibited IC50 values of 1.40 ± 0.113 and 0.358 ± 0.130 μM, respectively.

Abstract 1343: Association between IL1B gene haplotypes and colorectal cancer risk in Colombian populations: a case-control study.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Single nucleotide polymorphisms (SNPs) in cytokines can affect gene expression causing an effect in inflammation and carcinogenesis. There are conflicting results in the association between IL1B gene markers with colorectal cancer (CRC). Most reports on the association of IL1B and CRC have analysed individual SNPs despite several studies have implied that studying the haplotype context is important to understand the biological effect in IL1B gene expression and carcinogenesis. Aim: To evaluate the association of CRC and adenomatous polyps (AP) with IL1B haplotypes in Colombian populations Methods: 308 CRC cases, 208 AP and 524 age-sex matched controls were recruited from six Colombian cities with different CRC risk in a multicenter hospital-based case-control study aiming at identifying the environmental and genetic risk factors for CRC in Colombia. Participants gave written informed consent, donated blood samples and answered guided-questionnaires. Subjects were genotyped for IL1B SNPs: -31, +3954, -3737, -1464 and -511 using TaqMan® SNP Genotyping Assays. Hardy-Weinberg Equilibrium (HWE) was assessed and statistical analysis was done using conditional logistic regression adjusting for risk factors and genetic ancestry. Linkage disequilibrium (LD) was calculated using Haploview 4.0 and D’ and r2 statistics. Recessive and codominant models were explored for haplotype analysis using STATA v11.0. The Ethics Board of The National Cancer Institute of Colombia approved this study Results: Among controls all IL1B SNPs were in HWE (p>0.05). We found one haplotype block including all 4 SNPs in the IL1B gene, except the IL1B+3954 SNP which was left out (MAF=0,14). IL1B-31 and IL1B-511 showed to be in high LD (D’: 0,998; r2: 0,948). Under recessive model, we found an association with an increased risk for PA and CRC with the -31C/-511T/-1464G/-3737C haplotype (OR 2.42 IC 1.21 - 4.84 p<0.01). Stratified analysis of PA and CRC risk separately, showed similar results. This risk decreases when the rare allele of the -1464C was also present in the haplotype (p 0.05). These associations persist after adjusting for confounding Conclusions: The -31C/-511T/-1464G/-3737C haplotype was associated with premalignant and malignant lesions in colon and rectum, interesting the effect of the rare alleles -31C and -511T was countered by the -1464C allele since the haplotype -31C/-511T/-1464C/-3737C showed no association with the disease. These findings are correlated with functional assay studies in which the former haplotype increase promoter activity of the IL1B gene and the later decrease that effect supporting the importance of understanding the haplotype context in association studies. These associations with the disease remained after corrected by Caucasian and African ancestry, meaning that these are true and not due to differences in the genetic background of the Colombian population Citation Format: Maria Carolina Sanabria-Salas, Gustavo Hernandez-Suarez, Adriana Umana, Martha Lucia Serrano Lopez, Myriam Y. Sanchez, Martha P. Rojas, Jovanny Zabaleta. Association between IL1B gene haplotypes and colorectal cancer risk in Colombian populations: a case-control study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1343. doi:10.1158/1538-7445.AM2013-1343

Vías de carcinogénesis colorrectal y sus implicaciones clínicas

Resumen El cancer colorrectal (CCR) es la cuarta causa de mortalidad por cancer en Colombia y en el mundo, en ambos sexos; por esta razon, es considerado un problema de salud publica. El CCR es altamente heterogeneo en su fenotipo y genotipo, lo que esta en relacion con las diferentes vias de carcinogenesis descritas que implican diferentes mecanismos de progresion y agresividad de la enfermedad. Las vias clasicas, supresora y mutadora, se caracterizan por una serie de alteraciones geneticas relacionadas con los cambios fenotipicos de la progresion morfologica en la secuencia adenoma-carcinoma. Las vias alternas, originadas por mutaciones en los genes, BRAF y KRAS , se relacionan con la progresion de polipo aserrado a carcinoma. Conocer estas vias es muy importante para comprender la enfermedad de manera integral y profundizar en el estudio de sus mecanismos de control, que incluyen: diagnostico temprano, tratamiento y seguimiento.