Open Access
Actionable driver events in small cell lung cancer
(MDPI, 2024) Gutiérrez Núñez, Mirian; Zamora Álvarez, Irene; Freeman, Michael R.; Encío Martínez, Ignacio; Rotinen Díaz, Mirja Sofia; Ciencias de la Salud; Osasun Zientziak
Small cell lung cancer (SCLC) stands out as the most aggressive form of lung cancer, characterized by an extremely high proliferation rate and a very poor prognosis, with a 5-year survival rate that falls below 7%. Approximately two-thirds of patients receive their diagnosis when the disease has already reached a metastatic or extensive stage, leaving chemotherapy as the remaining first-line treatment option. Other than the recent advances in immunotherapy, which have shown moderate results, SCLC patients cannot yet benefit from any approved targeted therapy, meaning that this cancer remains treated as a uniform entity, disregarding intra- or inter-tumoral heterogeneity. Continuous efforts and technological improvements have enabled the identification of new potential targets that could be used to implement novel therapeutic strategies. In this review, we provide an overview of the most recent approaches for SCLC treatment, providing an extensive compilation of the targeted therapies that are currently under clinical evaluation and inhibitor molecules with promising results in vitro and in vivo.
Open Access
Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
(Elsevier, 2022) Ramos Inza, Sandra; Encío Martínez, Ignacio; Raza, Asif; Sharma, Arun K.; Sanmartín, Carmen; Plano, Daniel; Ciencias de la Salud; Osasun Zientziak; Institute for Multidisciplinary Research in Applied Biology - IMAB
A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI's panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer.
Open Access
A novel prognostic biomarker panel for early‐stage colon carcinoma
(MDPI, 2021) Azcue Sanromán, Pablo; Guerrero Setas, David; Encío Martínez, Ignacio; Ibáñez Beroiz, Berta; Mercado Gutiérrez, María R.; Vera García, Ruth; Gómez Dorronsoro, María Luisa; Ciencias de la Salud; Osasun Zientziak
Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early‐stage colon cancer (CC). The purpose of this study was to assess PD‐L1, GLUT‐1, e‐cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk‐panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD‐L1, GLUT‐1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low‐risk patients, medium‐risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high‐risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early‐stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.
Open Access
Antidiabetic effects of Pediococcus acidilactici pA1c on HFD-induced mice
(MDPI, 2022) Cabello Olmo, Miriam; Oneca Agurruza, María; Pajares Villandiego, María Josefa; Jiménez, Maddalen; Ayo, Josune; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 0011-1365-2020-000086
Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.
Open Access
Human microbiota network: unveiling potential crosstalk between the different microbiota ecosystems and their role in health and disease
(MDPI, 2021) Martínez, José E.; Vargas González, Augusto; Pérez Sánchez, Tania; Encío Martínez, Ignacio; Cabello Olmo, Miriam; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak
The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies.
Open Access
A combination of apple vinegar drink with Bacillus coagulans ameliorates high fat diet-induced body weight gain, insulin resistance and hepatic steatosis
(MDPI, 2020) Urtasun Alonso, Raquel; Araña Ciordia, Miriam; Pajares Villandiego, María Josefa; Oneca Agurruza, María; Torre Hernández, Paloma; Barajas Vélez, Miguel Ángel; Encío Martínez, Ignacio; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.
Open Access
Influence of storage temperature and packaging on bacteria and yeast viability in a plant-based fermented food
(MDPI, 2020) Cabello Olmo, Miriam; Oneca Agurruza, María; Torre Hernández, Paloma; Díaz, Jesús Vicente; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura; Gobierno de Navarra / Nafarroako Gobernua
Optimization of food storage has become a central issue for food science and biotechnology, especially in the field of functional foods. The aim of this work was to investigate the influence of different storage strategies in a fermented food product (FFP) and further determine whether the regular storage (room temperature (RT) and standard packaging (SP)) could be refined. Eight experimental conditions (four different temperatures × two packaging) were simulated and changes in FFP’s microbial ecology (total bacteria, lactic acid bacteria (LAB), and yeasts) and physicochemical characteristics (pH and moisture content (MC)) were determined following 1, 3, 6, and 12 months. All conditions tested showed a decline in microbial content due to the effect of the temperature, 37 ◦C being the most detrimental condition, while −20 and 4 ◦C seemed to be better than RT in some parameters. Vacuum packaging (VP) only had a major effect on MC and we found that VP preserved greater MC values than SP at 3, 6, and 12 months. The correlation analysis revealed that total bacteria, LAB, and yeasts were positively associated, and also both pH and MC showed a correlation. According to our results and with the purpose to maintain the load of viable microorganisms, we observed that the best storage conditions should contemplate SP and freezing or cooling temperature during a period no longer than 3 months.
Open Access
Changes in gene expression profiling of apoptotic genes in neuroblastoma cell lines upon retinoic acid treatment
(Public Library of Science, 2013) Celay Leoz, Ion; Blanco Luquin, Idoia; Lázcoz Ripoll, Paula; Rotinen Díaz, Mirja Sofia; Castresana, Javier S.; Encío Martínez, Ignacio; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
To determine the effect of retinoic acid (RA) in neuroblastoma we treated RA sensitive neuroblastoma cell lines with 9-cis RA or ATRA for 9 days, or for 5 days followed by absence of RA for another 4 days. Both isomers induced apoptosis and reduced cell density as a result of cell differentiation and/or apoptosis. Flow cytometry revealed that 9-cis RA induced apoptosis more effectively than ATRA. The expression profile of apoptosis and survival pathways was cell line specific and depended on the isomer used.
Open Access
Cutting down on lung cancer: Ecliptasaponin A is a novel therapeutic agent
(AME, 2020) Rotinen Díaz, Mirja Sofia; Encío Martínez, Ignacio; Ciencias de la Salud; Osasun Zientziak
This article is a comment of 'Han J, Lv W, Sheng H, et al. Ecliptasaponin A induces apoptosis through the activation of ASK1/JNK pathway and autophagy in human lung cancer cells. Ann Transl Med 2019;7:539'.
Open Access
PD-L1 as a prognostic factor in early-stage colon carcinoma within the immunohistochemical molecular subtype classification
(MDPI, 2021) Azcue Sanromán, Pablo; Encío Martínez, Ignacio; Guerrero Setas, David; Suárez Alecha, Javier; Galbete Jiménez, Arkaitz; Mercado Gutiérrez, María R.; Vera García, Ruth; Gómez Dorronsoro, María Luisa; Ciencias de la Salud; Osasun Zientziak
Colorectal cancer (CRC) is a very heterogeneous disease. Efforts to characterize and search for biomarkers for these patients are currently ongoing in the hope of establishing a more targeted therapeutic approach. The role of PD-1 ligand (PD-L1) expression as a biomarker has not yet been fully elucidated. The Consensus Molecular Subtype classification has been delineated, but although already acknowledged in the most recent international guidelines, it has yet to be implemented in clinical practice. We investigate PD-L1 expression as a biomarker of prognosis in the early-stage setting and integrate it with the Consensus Molecular Subtype (CMS), in an effort to differentiate those patients with a worse prognosis who could potentially benefit from an early, more aggressive treatment. Our results suggest PD-L1 as an independent prognostic factor in early stage setting when assessed by immunohistochemistry. Additionally, PD-L1 expression appears to be a viable biomarker to differentiate patients in the CMS (CMS2/CMS3) who lack a clear prognosis.