- ItemOpen AccessMetformin exhibits antineoplastic effects on Pten-deficient endometrial cancer by interfering with TGF-β and p38/ERK MAPK signalling(Elsevier, 2023) Ruiz Mitjana, Anna; Vidal Sabanés, Maria; Navaridas Fernández de Bobadilla, Raúl; Perramon Güell, Aida; Yeramian Hakim, Andree; Nicholson Sabaté, Nathan; Egea Navarro, Joaquim; Encinas Martín, Mario; Matias-Guiu, Xavier; Dolcet Roca, XavierMetformin is a widespread antidiabetic agent that is commonly used as a treatment against type 2 diabetes mellitus patients. Regarding its therapeutic potential, multiple studies have concluded that Metformin exhibits antineoplastic activity on several types of cancer, including endometrial carcinoma. Although Metformin’s antineoplastic activity is well documented, its cellular and molecular anticancer mechanisms are still a matter of controversy because a plethora of anticancer mechanisms have been proposed for different cancer cell types. In this study, we addressed the cellular and molecular mechanisms of Metformin’s antineoplastic activity by using both in vitro and in vivo studies of Pten-loss driven carcinoma mouse models. In vivo, Metformin reduced endometrial neoplasia initiated by Pten-deficiency. Our in vitro studies using Pten-deficient endometrial organoids focused on both cellular and molecular levels in Metformin’s tumor suppressive action. At cellular level, we showed that Metformin is involved in not only the proliferation of endometrial epithelial cells but also their regulation via a variety of mechanisms of epithelial-to-mesenchymal transition (EMT) as well as TGF-β-induced apoptosis. At the molecular level, Metformin was shown to affect the TGF-β signalling., a widely known signal that plays a pivotal role in endometrial carcinogenesis. In this respect, Metformin restored TGF-β-induced apoptosis of Pten-deficient endometrial organoids through a p38-dependent mechanism and inhibited TGF-β-induced EMT on no-polarized endometrial epithelial cells by inhibiting ERK/MAPK signalling. These results provide new insights into the link between the cellular and molecular mechanism for Metformin’s antineoplastic activity in Pten-deficient endometrial cancers.
- ItemOpen AccessValidation of Modaplex POLE mutation assay in endometrial carcinoma(Springer, 2023) Dorca, Eduard; Velasco, Ana; Varela, Mar; Gatius Calderó, Sònia; Villatoro, Sergio; Fullana, Neus; Cuevas Sánchez, Dolors; Vaquero Susagna, Marta; Birnbaum, Astrid; Neumann, Karsten; Matias-Guiu, XavierThe TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing, techniques that are not available in many centers worldwide). In this study, we validate a novel method that allows simultaneous analysis of multiple pathogenic POLE mutations. The Modaplex technology integrates polymerase chain reaction and capillary electrophoresis. The design of this study encompassed 4 different steps: (1) a retrospective-pilot phase, with 80 tumors, balancing the four molecular subgroups. (2) A retrospective phase of 25 tumors obtained between 2016 and 2020, and 30 tumors obtained between 2000 and 2015. (3) An inter-laboratory corssavalidation step with 19 cases (belonging to phases 1 and 2). (4) A prospective cohort of 123 tumors, of unknown POLE status, with simultaneous validation by Sanger sequencing. A total of 258 samples were analyzed. In the first and second phases, the test showed positive/negative predictive values of 100%, by correctly identifying POLE mutation status in 79/79 and 55/55 cases. Phase 3 showed 100% of inter-laboratory consistency. Phase 4 showed 16 positive samples out of the 123 prospective cases. Overall, the test has revealed sensitivity and specificity of 100%, identifying a total of 47 POLE-mutated tumors. We have shown that this technique allows faster and easier identification of multiple pathogenic POLE mutations with high robustness and confidence when comparing to other tests such as Sanger sequencing.
- ItemOpen AccessTwo successive outbreaks of acute gastroenteritis due to norovirus GII.6 in a holiday camp house(Nature Research, 2023) Alsedà Graells, Miquel; Godoy i García, Pere; Bach, Pilar; Soldevila, Núria; Cornejo Sánchez, Thais; Corominas, Laura; Grau, Maria; Domínguez García, ÀngelaWhen two outbreaks occur in the same institution within a short period of time, an important health and social concern is generated. Two gastroenteritis outbreaks occurring a week apart in the same facility were reported in Lleida, Spain, in 2018. The objective of this study was to describe the clinical, epidemiological and microbiological investigation carried out and to determine the risk factors. Demographic data, food consumption and symptoms were collected. Health inspections of the facility were carried out. Risk ratio and their 95% confidence intervals were estimated for the implication of each food consumed. The attack rate was 89.7% in the first outbreak and 69.6% in the second outbreak. The most frequent symptoms in the first and second outbreak were abdominal pain (88.5% and 100%, respectively), vomiting (80.8% and 87.5%, respectively) and nausea (69.2% and 81.3%, respectively). The first outbreak was associated with the consumption of a salad and the second with a cheese omelet. Norovirus GII.6 was detected by RT-PCR and sequenced in both groups of students and in the food handlers who prepared the meals. These results highlight the importance of exclusion from work of food handlers with gastroenteritis, the adequate availability of mechanisms for correct hand washing and the correct cleaning of surfaces.
- ItemOpen AccessThe Spanish Adaptation of the Palliative Performance Scale (Version 2) Among Cancer Patients at the End of Life: Psychometric Properties(Elsevier, 2017) Barallat Gimeno, Eva; Nabal Vicuña, Maria; Canal, Jaume; Trujillano Cabello, Javier; Gea Sánchez, Montserrat; Larkin, Philip; Downing, Michael G.Background Palliative Performance Scale (PPS) is a reliable tool to assess performance status in cancer patients receiving palliative care (PC). Spanish validated and culturally adapted tools are needed. Objectives The objectives are to develop PPS translation and cross-cultural adaptation into Spanish and to assess its psychometric properties. Design Translation process with cross-cultural adaptation to produce Spanish Palliative Performance Scale (PPS-SPANISH). Settings PC Team at one University hospital in Spain. Participants Fifteen advanced cancer patients (60 assessments) were included for PPS translation and validation and 250 patients for cross-sectional analysis. All participants were recruited at oncology ward, emergency area, and outpatient clinic by PC team professionals. Informed consent was given. Average age was 66.4 ± 13 years (60% men). Methods The process is designed in three steps. In Step 1, PPS translation and reverse translation into Spanish (three bilingual speakers) and linguistic complexity measurement were performed. In Step 2, readability and intelligibility assessment was carried out. In Step 3, a pilot study was conducted to assess test-retest reliability followed by a cross-sectional study to measure internal consistency. Inclusion criteria were the same for two samples. Demographic data were also analyzed by descriptive statistics. Results Following cultural, linguistic, and grammatical adaptation, PPS-SPANISH was readable and reliable. The analysis of the test-retest reliability after 48 hours showed intraclass correlations >0.60. Cronbach's alpha coefficient was 0.99 (0.988–0.992). There was high agreement with other functional assessment tools (Barthel Index and Karnofsky Performance Status Index). Conclusions PPS-SPANISH showed reliability and validity, and it is suitable to assess performance status in cancer patients receiving PC.
- ItemOpen AccessCorrection to: Type 2 diabetes-associated carotid plaque burden is increased in patients with retinopathy compared to those without retinopathy(BioMed Central, 2018) Alonso, Núria; Traveset Maeso, Alicia; Rubinat, Esther; Ortega, Emilio; Alcubierre Calvo, Núria; Sanahuja Montesinos, Jordi; Hernández García, Marta; Betriu i Bars, M. Àngels; Jurjo Campo, Carmen; Fernández i Giráldez, Elvira; Mauricio Puente, Dídac