OBJECTIVE:Genomic instability is a hallmark of malignant tissues. In this work, we aimed to characterize nuclear and mitochondrial instabilities by determining short tandem repeats and somatic mitochondrial mutations, respectively, in a cohort of Brazilian sporadic breast cancer cases. Furthermore, we performed an association analysis of the molecular findings and the clinical pathological data.METHODS:We analyzed 64 matched pairs of breast cancer and adjacent non-cancerous breast samples by genotyping 13 nuclear short tandem repeat loci (namely, D2S123, TPOX, D3S1358, D3S1611, FGA, D7S820, TH01, D13S317, D13S790, D16S539, D17S796, intron 12 BRCA1 and intron 1 TP53) that were amplified with the fluorescent AmpFlSTR Identifiler Genotyping system (Applied Biosystems, USA) and by silver nitrate staining following 6% denaturing polyacrylamide gel electrophoresis. Somatic mtDNA mutations in the D-loop site were assessed with direct sequencing of the hypervariable HVI and HVII mitochondrial regions.RESULTS:Half of the cancer tissues presented some nuclear instability. Interestingly, the D13S790 locus was the most frequently affected (36%), while the D2S123 locus presented no alterations. Forty-two percent of the cases showed somatic mitochondrial mutations, the majority at region 303-315 poly-C. We identified associations between Elston grade III, instabilities at 13q31 region (p = 0.0264) and mtDNA mutations (p = 0.0041). Furthermore, instabilities at 13q31 region were also associated with TP53 mutations in the invasive ductal carcinoma cases (p = 0.0207).CONCLUSION:Instabilities at 13q31 region and the presence of somatic mtDNA mutations in a D-loop site correlated with tumor aggressiveness.
IntroductionThe trematode Schistosoma mansoni causes schistosomiasis, and this parasite’s life cycle depends on the mollusk Biomphalaria glabrata. The most effective treatment for infected people is administering a single dose of Praziquantel. However, there are naturally resistant to treatment. This work has developed, considering this parasite’s complex life cycle.MethodsThe synthetics compound were evaluated: i) during the infection of B. glabrata, ii) during the infection of BALB/c mice, and iii) during the treatment of mice infected with S. mansoni.Results and DiscussionFor the first objective, snails infected with miracidia treated with compounds C1 and C3 at concentrations of 25% IC50 and 50% IC50, after 80 days of infection, released fewer cercariae than the infected group without treatment. For the second objective, compounds C1 and C3 did not show significant results in the infected group without treatment. For the third objective, the mice treated with C3 and C1 reduced the global and differential cell count. The results suggest that although the evaluated compounds do not present schistosomicidal properties when placed in cercariae suspension, they can stimulate an immune reaction in snails and decrease mice’s inflammatory response. In general, we can conclude that compound C1 and C3 has an anti-schistosomicidal effect both in the larval phase (miracidia) and in the adult form of the parasite.
O mangue é um ecossistema de transição entre o ambiente terrestre e o marinho, típico de regiões tropicais e subtropicais. O cerrado é um ecossistema caracterizado principalmente pelo bioma savana, que são zonas de transição entre prados e bosques e são ínsitos de regiões tropicais de estação seca. Nesses dois sistemas, diversos microrganismos já foram isolados, entre eles, os fungos endofíticos, capazes de produzir substâncias com atividades antimicrobianas e leishmanicidas. Com base nessas informações, esse trabalho teve como objetivo avaliar o potencial biotecnológico dos extratos brutos (EB) obtidos dos fungos endofíticos Diaporthe sp. e Pseudofusicoccum sp., isolados de mangue e cerrado brasileiros, respectivamente. Foram realizados in vitro ensaios antimicrobianos com patógenos humanos, ensaios leishmanicidas e ensaios citotóxicos. Nos ensaios antimicrobianos foi encontrada a concentração inibitória mínima de 50% (CIM50) entre 756 µg.mL-1 e 949 µg.mL-1 e a concentração inibitória mínima de 90% (CIM90) entre 3.940 e 3.980 µg.mL-1 para o EB do isolado do mangue. Para o EB isolado do cerrado foi encontrada CIM50 entre 4.228 µg.mL-1 e 29.630 µg.mL-1 e CIM90 entre 9.24 µg.mL-1 e 38.250 µg.mL-1. A concentração bactericida mínima (CBM) foi encontrada para o microrganismo Bacillus subtillis, na concentração de 10.000 µg.mL-1. Nos ensaios leishmanicidas, os resultados apresentam morte celular de 90% nas concentrações de 6.000 e 10.000 µg.mL-1 e de 80% na concentração de 4.000 µg.mL-1 para o EB do isolado do mangue. No EB do isolado do cerrado, os ensaios leishmanicidas apresentaram viabilidade celular acima de 90% nas concentrações de 20.000 e 40.000 µg.mL-1. Para os ensaios de citotoxicidade no EB do isolado do mangue, foram apresentados viabilidade celular entre 55 e 73%. Para o isolado do cerrado foram apresentadas viabilidade celular entre 5,41 a 16,84%. Esses resultados reforçam o potencial biotecnológico dos microrganismos isolados de manguezais e cerrados, representado pelos isolados testados nesse trabalho.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.