View metadata, citation and similar papers at core.ac.uk provided by EPrints Complutense Página 2... more View metadata, citation and similar papers at core.ac.uk provided by EPrints Complutense Página 2 de 24 Resumen: A día de hoy, la infección por VIH es crónica pese a la mejora de la terapia antirretroviral (TAR), debido a la presencia de reservorios en los cuales el virus permanece oculto del sistema inmunitario y de los fármacos antirretrovirales. Por ello, en pacientes en los cuales se ha logrado controlar la infección mediante la TAR se busca dar un paso más y eliminar estos reservorios para así poder eliminar la infección. Entre las estrategias investigadas con este fin se encuentra la llamada "shock and kill", que consiste en el empleo de agentes revertidores de latencia o LRAs para inducir la expresión del virus latente en los reservorios, de forma que éstos puedan identificarse como células infectadas y puedan ser eliminados. Tras revisar varios estudios publicados en las base de datos PMC y ClinicalTrials.gov, se ha encontrado que existen varios grupos de compuestos que constituyen potenciales LRAs útiles, entre ellos los agonistas de PKC y los HDACis han adquirido bastante protagonismo. Sin embargo, pese a que existen compuestos que han demostrado inducir la expresión de los provirus en pacientes, a día de hoy no se ha encontrado un compuesto que por sí solo haya demostrado llevar a la reducción del reservorio viral del organismo. El futuro parece estar en el empleo de combinaciones sinérgicas de fármacos. También se plantea la posibilidad de combinar el empleo de LRAs y vacunas para reforzar la eliminación inmunitaria.
This work aims to investigate the expression levels of four preselected miRNAs previously linked ... more This work aims to investigate the expression levels of four preselected miRNAs previously linked to cancer and/or obesity, with the purpose of finding potential biomarkers in the clinical management of CRC developed by patients showing different BMI values. We analyzed samples from a total of 65 subjects: 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were investigated, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2−∆∆Ct) levels of 4 miRNAs (hsa-miR-181a-5p, hsa-miR-143-3p, has-miR-132-3p and hsa-miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC, serum levels of hsa-miR-143-3p clearly correlated with their levels in both SAT and OAT, independently of the BMI group. Moreover, hsa-miR-181a-...
Potential Utility of a Panel of Four-miRNAs As Biomarkers in the Clinical Management of Obese and Non-obese Colorectal Cancer Patients
This work aims to investigate the expression levels of four preselected miRNAs previously linked ... more This work aims to investigate the expression levels of four preselected miRNAs previously linked to Cancer and/or Obesity, with the purpose of finding potential biomarkers in the clinical management of Colorectal Cancer (CRC) developed by obese and non-obese patients. We analyzed samples from a total of 65 subjects, 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were analyzed, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (miR-181a-5p, miR-143-3p, miR-132-3p and miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC serum levels of miR-181a-5p, miR-143-3p and miR-23a-3p correlated with their levels in both SAT and OAT. Moreover, in the case of miR-181a-5p, these corre...
The risk associated with obesity for the development of colorectal cancer seems to be well establ... more The risk associated with obesity for the development of colorectal cancer seems to be well established. However, no biomarkers have been defined that allow the degree of obesity to be related to the clinical evolution of individuals affected by colorectal cancer. With the aim of contributing to the development of this correlation, we carried out a prospective study investigating parameters related to telomere function in the subcutaneous and visceral adipose tissues of a total of 147 subjects affected and not affected by colorectal cancer. Both the relative telomere length and the activity of telomerase in the adipose tissues seem to constitute parameters of interest in the clinical evaluation of individuals with colorectal cancer, which could be also related to the body mass index.
The risk of colorectal cancer (CRC) development has been associated with telomere dysfunction and... more The risk of colorectal cancer (CRC) development has been associated with telomere dysfunction and obesity. However, clinical relevance of these parameters in CRC prognosis is not clear. Therefore, the aim of the present study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. According to published data, this is the first work in which obesity and telomere status are jointly considered in relation to CRC prognosis. A prospective study including 162 patients with CRC submitted to curative surgical treatment was performed. Subjects were classified according to their BMI. Telomere status was established through telomere length and telomerase activity evaluation. Statistical analyses were performed using the SPSS software package version 22. Telomere shortening was inversely associated with BMI in patients with CRC. Notably, among patients with CRC, subjects with obesity exhibited less shortening of tumor telomeres than non-obese patients (P=0.047). Patients with shorter telomeres, both in the tumor (median telomere length <6.5 kb) and their non-tumor paired tissues (median telomere length <7.1 kb), had the best clinical evolution, regardless of the Dukes' stage of cancers (P=0.025, for tumor samples; P= 0.003, for non-tumor samples). Additionally, subjects with a BMI >31.85 kg/m 2 showed the worse clinical outcomes compared with subjects with other BMI values. Interestingly, the impact of BMI showed sex dependence, since only the group of men displayed significant differences in CRC prognosis in relation to obesity status (P=0.037). From the results of the present study, based on a multivariate prediction model to establish prognosis, it was concluded that telomere length is a useful biomarker to predict prognosis in patients with CRC. Regardless of BMI values, the improved clinical evolution was associated with shorter telomeres. The impact of BMI seems to be associated with other factors, such as sex.
The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging... more The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis.
Expression Analysis of hsa-miR-181a-5p, hsa-miR-143-3p, hsa-miR-132-3p and hsa-miR-23a-3p as Biom... more Expression Analysis of hsa-miR-181a-5p, hsa-miR-143-3p, hsa-miR-132-3p and hsa-miR-23a-3p as Biomarkers in Colorectal Cancer-Relationship to the
Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CR... more Microbiota could be of interest in the diagnosis of colorectal and non-small cell lung cancer (CRC and NSCLC). However, how the microbial components of tissues and feces reflect each other remains unknown. In this work, our main objective is to discover the degree of correlation between the composition of the tissue microbiota and that of the feces of patients affected by CRC and NSCLC. Specifically, we investigated tumor and non-tumor tissues from 38 recruited patients with CRC and 19 with NSCLC. DNA from samples was submitted for 16S rDNA metagenomic sequencing, followed by data analysis through the QIIME2 pipeline and further statistical processing with STATA IC16. Tumor and non-tumor tissue selected genera were highly correlated in both CRC and NSCLC (100% and 81.25%). Following this, we established tissue-feces correlations, using selected genera from a LEfSe analysis previously published. In CRC, we found a strong correlation between the taxa detected in feces and those from colorectal tissues. However, our data do not demonstrate this correlation in NSCLC. In conclusion, our findings strongly reinforce the utility of fecal microbiota as a non-invasive biomarker for CRC diagnosis, while highlighting critical distinctions for NSCLC. Furthermore, our data demonstrate that the microbiota components of tumor and non-tumor tissues are similar, with only minor differences being detected.
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Papers by Sofia Tesolato