Person: Iniesta Serrano, María Pilar
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First Name
María Pilar
Last Name
Iniesta Serrano
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
7 results
Search Results
Now showing 1 - 7 of 7
Item Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer(PLOS ONE, 2016) Fernández-Marcelo, Tamara; Sánchez Pernaute, Andrés; Pascua, Irene; Juan Chocano, María Del Carmen De; Head, Jacqueline; Torres García, Antonio José; Iniesta Serrano, María Pilar; Michel M OuelletteThe role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.Item Poly (ADP-ribose) polymerase 3 (PARP3), a potential repressor of telomerase activity(Journal of Experimental & Clinical Cancer Research, 2014) Fernández-Marcelo, Tamara; Frías, Cristina; Pascua, Irene; Juan Chocano, María Del Carmen De; Head, Jacqueline; Gómez, Ana; Hernando Trancho, Florentino; Jarabo Sarceda, José Ramón; Díaz-Rubio García, Eduardo; Torres García, Antonio José; Rouleau, Michèle; Benito De Las Heras, Manuel R.; Iniesta, Pilar; Iniesta Serrano, María PilarBackground Considering previous result in Non-Small Cell Lung Cancer (NSCLC), we investigated in human cancer cells the role of PARP3 in the regulation of telomerase activity. Methods We selected A549 (lung adenocarcinoma cell line) and Saos-2 (osteosarcoma cell line), with high and low telomerase activity levels, respectively. The first one was transfected using a plasmid construction containing a PARP3 sequence, whereas the Saos-2 cells were submitted to shRNA transfection to get PARP3 depletion. PARP3 expression on both cell systems was evaluated by real-time quantitative PCR and PARP3 protein levels, by Western-blot. Telomerase activity was determined by TRAP assay. Results In A549 cells, after PARP3 transient transfection, data obtained indicated that twenty-four hours after transfection, up to 100-fold increased gene expression levels were found in the transfected cells with pcDNA/GW-53/PARP3 in comparison to transfected cells with the empty vector. Moreover, 48 hours post-transfection, telomerase activity decreased around 33%, and around 27%, 96 hours post-transfection. Telomerase activity average ratio was 0.67 ± 0.05, and 0.73 ± 0.06, respectively, with significant differences. In Saos-2 cells, after shRNA-mediated PARP3 silencing, a 2.3-fold increase in telomerase activity was detected in relation to the control. Conclusion Our data indicated that, at least in some cancer cells, repression of PARP3 could be responsible for an increased telomerase activity, this fact contributing to telomere maintenance and, therefore, avoiding genome instability.Item 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 Body Mass Index(Cancers, 2023) Tesolato, Sofía; González-Gamo, Daniel; Barabash Bustelo, Ana; Claver, Paula; De La-Serna Esteban, Sofía Cristina; Domínguez Serrano, María Inmaculada; Dziakova, Jana; Juan Chocano, María Del Carmen De; Torres García, Antonio José; Iniesta Serrano, María Pilar; Sterpetti, Antonio V.Colorectal cancer (CRC) is one of the main tumor pathologies in our society considering its incidence and mortality. Various authors have linked the development of CRC with overweight and obesity. However, no molecular markers have been defined to connect both pathologies and that can be assessed in serum for diagnostic and/or prognostic purposes. The main objective of this work is to analyze and correlate the expression levels of four miRNAs previously associated with cancer and/or obesity in patients affected by CRC, as well as in a control group without cancer, considering the body mass index (BMI) of subjects. The main novelty of this study consists in the variety of samples investigated: adipose tissues, omental and subcutaneous; serum; and tumor and non-tumor tissues in the case of CRC patients. Results conclude about the utility mainly of hsa-miR-143-3p and hsa-miR-181a-5p in the clinical management of CRC.Item Obesity and telomere status in the prognosis of patients with colorectal cancer submitted to curative intention surgical treatment(Molecular and Clinical Onclogy, 2021) García Martínez, Sergio; González Gamo, Daniel; Fernández Marcelo, Tamara; Tesolato, Sofía; De La-Serna Esteban, Sofía Cristina; Domínguez Serrano, María Inmaculada; Cano Valderrama, Óscar; Barabash Bustelo, Ana; Juan Chocano, María Del Carmen De; Torres García, Antonio José; Iniesta Serrano, María PilarThe 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/m2 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.Item Variation of microbiota depending on the location of colorectal cancer(2024) Picaporte Fuentes, Pablo; Dziakova, Jana; De La-Serna Esteban, Sofía Cristina; Jaimes, E.; García Galocha, José Luis; Rivera, D.; Iniesta Serrano, María Pilar; Torres García, Antonio JoséColorectal cancer (CRC) growth may be determined by various factors, with gut microbiota being one of them. The aim of this study is to Identify the microbiota differences in tumoral tissue (TT), non-tumoral tissue (NTT) and feces depending on CRC localization. Prospective analysis was conducted on patients with CRC who underwent colorectal surgery in 2021 and 2022. Three samples were collected from each patient: feces, tissue from tumor (TT), and tissue from healthy colon (NTT). The study employed 16S rRNA massive sequencing techniques, followed by bioinformatics analyses. A total of 23 patients, comprising 18 males and 5 females, were included in the study. Tumor distribution revealed 12 cases in the right colon, 7 in the left colon, and 4 in the rectum. Significant differences were observed in beta diversity between the microbiota of feces and both types of tissue (TT and NTT). However, no differences in beta diversity were noted between TT and NTT. NTT exhibited a predominance of the phylum Actinobacteriota, while Bacteroidetes was the main phylum in feces. TT was characterized by a higher proportion of Fusobacteriota, with the genera Fusobacteria and Streptococcus being predominant compared to feces and genus Fusobacteria compared to NTT. When considering tumor location, notable differences emerged. There was greater microbiota diversity in the right colon compared to the left colon and rectum. Phyla Clostridiales, Bifidobacteriales, Acidaminococcales, and Vibrionales were more abundant in the right colon, while Staphylococcales were more prevalent in the left colon. The observed variations in microbiota based on tissue type and location imply its potential involvement in colorectal cancer (CRC) pathogenesis.Item Gut Microbiota Signatures with Potential Clinical Usefulness in Colorectal and Non-Small Cell Lung Cancers(Biomedicines, 2024) Tesolato, Sofía; Vicente Valor, Juan; Paz Cabezas, Mateo; Gómez Garre, Dulcenombre; Sánchez González, Silvia; Ortega Hernández, Adriana; De La-Serna Esteban, Sofía Cristina; Domínguez Serrano, María Inmaculada; Dzyakova, Jana; Rivera, Daniel; Jarabo Sarceda, José Ramón; Gómez Martínez, Ana María; Hernando Trancho, Florentino; Torres García, Antonio José; Iniesta Serrano, María Pilar; Ryota NiikuraThe 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.Item Telomere Length and Telomerase Activity in Subcutaneous and Visceral Adipose Tissues from Obese and Non-Obese Patients with and without Colorectal Cancer(Cancers, 2022) García Martínez, Sergio; González Gamo, Daniel; Tesolato, Sofía Elena; Barabash Bustelo, Ana; De La-Serna Esteban, Sofía Cristina; Domínguez Serrano, María Inmaculada; Dziakova, Jana; Rivera, Daniel; Torres García, Antonio José; Iniesta Serrano, María Pilar; Luis M. MontuengaTo investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.