We compared the levels of AURKA and AURKB in 24 (mantle cell lymphoma) MCL patients harboring 8q abnormalities and its relationship with MYCC gene status. Two distinct subgroups were observed, in terms of MYCC expression. Except for the patients with Burkitt's-like translocation, none of the patients harboring 8q abnormalities, including balanced translocations or duplications of MYCC band, identified both by G-banding and SKY, showed differential expression levels of MYCC. These previous findings also reflected in the differential expression of AURKA and AURKB genes. We found that AURKA and AURKB mRNA were expressed at significantly higher levels in MCL patients harboring Burkitt's-like translocation, when compared to patients with 8q rearrangements. The high expression of aurora kinase genes is reported to be associated with some parameters of clinical oncologic aggressiveness, such as high histological grade, invasion and increased rates of metastasis in several types of cancers. It is possible that in MCL patients expressing abnormal levels of MYCC together with a high expression of AURKA might offer some resistant to the conventional therapy purposes. Thus, aurora kinase inhibitors may also be considered for this specific subgroup on MCL, whose aggressive clinical course resembles high-grade lymphoma.
BackgroundTrypanosoma cruzi is the causative agent of Chagas disease, which is endemic to subtropical and tropical Americas. The disease treatment remains partially ineffective, involving therapies directed to the parasite as well as palliative strategies for the clinical manifestations. Therefore, novel candidates for disease control are necessary. Additionally, strategies based on parasite inhibition via specific targets and application of compounds which improve the immune response against the disease is welcomed. Ghrelin is a peptide hormone pointed as a substance with important cardioprotective, vasodilatory, anti-apoptotic, anti-oxidative and immune modulatory functions. The aims of this study were to evaluate the immunomodulatory effects of ghrelin in male Wistar rats infected with the Y strain of T. cruzi.MethodsIn order to delineate an immune response against T. cruzi mediated by ghrelin, we evaluated the following parameters: quantification of blood and cardiac parasites; analysis of cell markers (CD3+, CD8+, NK, NKT, CD45RA+, macrophage and RT1B+); nitric oxide (NO) production; lymphoproliferation assays; splenocyte apoptosis; and INF-γ, IL-12 and IL-6 quantification in sera.ResultsThe animals infected with T. cruzi and supplemented with ghrelin demonstrated an upregulated pattern in macrophage and NO production, whereas an anti-inflammatory response was observed in T cells and cytokines. The low response against T. cruzi mediated by T cells probably contributed to a higher colonization of the cardiac tissue, when compared to infected groups. On the other side, the peptide decreased the inflammatory infiltration in cardiac tissue infected with T. cruzi.ConclusionsGhrelin demonstrated a dual function in animals infected with T. cruzi. Further studies, especially related to the decrease of cardiac tissue inflammation, are needed in order to determine the advantages of ghrelin supplementation in Chagas disease, mostly for populations from endemic areas.
SILVA, F. P. Ghrelin: possible cardioprotective and immunomodulatory effects in acute experimental phase of Chaga's disease. 2017. 89f. Dissertation (Master).
2771 One major cause of genomic instability and cellular apoptosis is telomere dysfunction. Telomere loss or dysfunction results in breakage–bridge –fusion cycles, aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells: nuclei of the latter tend to be disorganized and commonly contain telomeric aggregates. However, few studies have addressed the impact of telomeres dynamics in CML progression. The frequency of additional chromosomal abnormalities in CML is around 5% in chronic phase and increases to 50–80% in the advanced phases. Clonal evolution often precedes progression and is predictive for inferior therapeutic outcome. In order to better understand cellular and molecular mechanisms in CML progression, the objectives of this investigation were examine telomere dysfunction and alterations in the 3D nuclear telomere architecture. Eighteen CML patients, in total, 54 bone marrow samples (chronic phase, accelerated phase and blast crisis) were eligible for 3D nuclear telomeric investigation. The quantitative FISH (QFISH), cytologic diagnosis and the cytogenetic determination for additional chromosomal abnormalities were assessed according to standard protocols. 3D image analysis on 30 interphase nuclei per slide was obtained by using an Axio Imager A1 microscope (Carl Zeiss, USA). Sixty z-stacks were acquired at a sampling distance of x,y: 102 nm and z: 200 nm for each slice of the stack. AxioVision 4.8 software (Carl Zeiss, Canada) was used for 3D image acquisition, and deconvolution analysis. Three CML subgroups were defined on the basis of their 3D telomeric profiles. The telomeric parameters (number, length, telomere aggregates and nuclear volumes) were compared between these three subgroups. Distribution of telomere intensities in CML phases was compared between the patient's subgroups. All patients of a same subgroup displayed similar 3D telomeric profiles. Comparison with clinical diagnosis after the classification according to telomere profile showed that all CML patients were classified in the three distinct subgroups. Statistical analyses showed significant differences between the CML subgroups (P<0.001). Each of the quantitative telomere parameters exhibited significant differences. Furthermore, statistical analyses combining all 3D telomere parameters revealed significant differences between all subgroups (P<0.05). According to our data these profiles are correlated to the disease evolution and increased telomere dysfunction in these subgroups. It seems that the evolution of CML progresses from low to high level of telomere dysfunction, that is, from early stage to more aggressive stage, followed by disease transformation. We concluded that telomere 3D organization is a highly accurate tool to distinguish CML stages. We propose that monitoring 3D telomere dysfunction might be a very powerful marker to measure this transformation. Furthermore, it may be a better indicator of therapeutic response because an optimal response will lead to a normal cellular biology, including elimination of abnormal telomeric aggregates and the increase of normal 3D telomeric profiles. Financial support: FAPESP (2011/01647-2). Disclosures: No relevant conflicts of interest to declare.
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.