Quantitative diffusion and perfusion MRI in the evaluation of endometrial cancer. Validation with histopathological parameters

Objectives: To investigate the role of quantitative Magnetic Resonance Imaging (MRI) in preoperative assessment of tumour aggressiveness in patients with endometrial cancer, correlating multiple parameters obtained from diffusion and dynamic contrast-enhanced (DCE) MR sequences with conventional histopathological prognostic factors and inflammatory tumour infiltrate.Methods: Forty-four patients with biopsy-proven endometrial cancer underwent preoperative MR imaging at 3T scanner, including DCE imaging, diffusion-weighted imaging (DWI) and intravoxel incoherent motion imaging (IVIM). Images were analysed on dedicated post-processing workstations and quantitative parameters were extracted: K-trans, K-ep, V-e and AUC from the DCE; ADC from DWI; diffusion D, pseudo diffusion D*, perfusion fraction f from IVIM and tumour volume from DWI. The following histopathological data were obtained after surgery: histological type, grading (G), lympho-vascular invasion (LVI), lymph node status, FIGO stage and inflammatory infiltrate.Results: ADC was significantly higher in endometrioid histology, G1-G2 (low grade), and stage IA. Significantly higher D* were found in endometrioid subptype, negative lymph nodes and stage IA. The absence of LVI is associated with higher f values. K-trans and V-e values were significantly higher in low grade. Higher D*, f and AUC occur with the presence of chronic inflammatory cells, D * was also able to distinguish chronic from mixed type of inflammation. Larger volume was significantly correlated with the presence of mixed-type inflammation, LVI, positive lymph nodes and stage >= IB.Conclusions: Quantitative biomarkers obtained from pre-operative DWI, IVIM and DCE-MR examination are an in vivo representation of the physiological and micro-structural characteristics of endometrial carcinoma allowing to obtain the fundamental parameters for stratification into Risk Classes.Advances in knowledge: Quantitative imaging biomarkers obtained from DWI, DCE and IVIM may improve preoperative prognostic stratification in patients with endometrial cancer leading to a more informed therapeutic choice

Otx015 epi‐drug exerts antitumor effects in ovarian cancer cells by blocking gnl3‐mediated radioresistance mechanisms: Cellular, molecular and computational evidence

Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra‐Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015‐mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC

Transcriptomic and genomic structural variation analyses on grape cultivars reveal new insights into the genotype-dependent responses to water stress

Grapevine (Vitis vinifera L.) is importantly cultivated worldwide for table grape and wine production. Its cultivation requires irrigation supply, especially in arid and semiarid areas. Water deficiency can affect berry and wine quality mostly depending on the extent of plant perceived stress, which is a cultivar-specific trait. We tested the physiological and molecular responses to water deficiency of two table grape cultivars, Italia and Autumn royal, and we highlighted their different adaptation. Microarray analyses revealed that Autumn royal reacts involving only 29 genes, related to plant stress response and ABA/hormone signal transduction, to modulate the response to water deficit. Instead, cultivar Italia orchestrates a very broad response (we found 1037 differentially expressed genes) that modifies the cell wall organization, carbohydrate metabolism, response to reactive oxygen species, hormones and osmotic stress. For the first time, we integrated transcriptomic data with cultivar-specific genomics and found that ABA-perception and –signalling are key factors mediating the varietal-specific behaviour of the early response to drought. We were thus able to isolate candidate genes for the genotype-dependent response to drought. These insights will allow the identification of reliable plant stress indicators and the definition of sustainable cultivar-specific protocols for water management

Calcineurin gamma catalytic subunit ppp3cc inhibition by mir-200c-3p affects apoptosis in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) outpaces all the other forms of the female reproductive system malignancies. MicroRNAs have emerged as promising predictive biomarkers to therapeutic treatments as their expression might characterize the tumor stage or grade. In EOC, miR-200c is considered a master regulator of oncogenes or tumor suppressors. To investigate novel miR-200c-3p target genes involved in EOC tumorigenesis, we evaluated the association between this miRNA and the mRNA expression of several potential target genes by RNA-seq data of both 46 EOC cell lines from Cancer Cell line Encyclopedia (CCLE) and 456 EOC patient bio-specimens from The Cancer Genome Atlas (TCGA). Both analyses showed a significant anticorrelation between miR-200c-3p and the protein phosphatase 3 catalytic subunit γ of calcineurin (PPP3CC) levels involved in the apoptosis pathway. Quantitative mRNA expression analysis in patient biopsies confirmed the inverse correlation between miR-200c-3p and PPP3CC levels. In vitro regulation of PPP3CC expression through miR-200c-3p and RNA interference technology led to a concomitant modulation of BCL2- and p-AKT-related pathways, suggesting the tumor suppressive role of PPP3CC in EOC. Our results suggest that inhibition of high expression of miR-200c-3p in EOC might lead to overexpression of the tumor suppressor PPP3CC and subsequent induction of apoptosis in EOC patients

Telemedicine will not keep us apart in COVID-19 pandemic

not applicabl

Vulvar lipoma: rare case, rare location

Background. Vulvar lipomas are very rare pathologies: indeed, only few cases are reported in the literature. Case presentation. We reported clinical, diagnostic and therapeutical choices of a 44-year aged patient with a rare abnormally sized vulvar lipoma. A Diamond-shaped skin incision was performed and the neoformation was removed without capsule lesions. A vaginal plastic skin-reducing was performed to reduce redundant tissue. The deep planes of the lesion have been reconstructed to avoid leakage. Conclusions. This kind of lipomas can be potentially diagnosed through clinical examination because of their specific characteristics. However, imaging is advisable to differentiate benign neoplasm from malignant one. Different approaches can be achieved for lipomas based on the size of lump, patient’s feelings and necessities and the operation goals; however, the complete surgical excision with the removal of capsules to prevent recurrence remains the treatment of choice for vulvar lipomas. Different surgical approaches aim to achieve better esthetical results, less scarring, and less colour discordance of the connected tissues post-surgery. Surgery is the gold standard for treatment of vulvar lesions. Currently, there is no evidence of long-term follow-up in the literature. We recommend an adequate counselling with the patient to understand their needs and encouraging them to seek medical advice and to tailor the treatment of such lesions

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory

FRI0110 Methotrexate monotherapy in real life: a drug survival analysis. comparison between very early arthritis and early arthritis cohorts

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Teacher performance evaluation: conflict, uncertainties and the search for meaning(s)

O texto que propomos parte de uma pesquisa longitudinal, realizada em Portugal entre 2008 e 2010, com professores do 1º Ciclo do Ensino Básico. Procura evidenciar os conflitos e incertezas que a avaliação do desempenho docente tem produzido e a busca de sentido(s) para esta avaliação e para o ‘ser professor/a’. A implementação de sistemas de avaliação do desempenho dos professores insere-se na procura de soluções para esta inquietação. Foi o que aconteceu em Portugal, em Janeiro de 2007, com a publicação em Diário da República do novo Estatuto da Carreira Docente e o Decreto que regulamentava a Avaliação do Desempenho Docente. As tensões emergiram entre docentes e Ministério da Educação, agudizaram-se com a tomada de consciência da problemática da avaliação do desempenho dos docentes com impacto na carreira profissional e provocaram incertezas e desmotivação face ao sentido do trabalho docente com impacto na identidade profissional dos professores.This article stems from a longitudinal research carried out with primary school teachers in Portugal between 2008 and 2010. The research sought to identify the conflicts and uncertainties, which have been caused by the evaluation of teacher performance, as well as to search for meaning(s) related to that evaluation and to ‘being a teacher’. The implementation of systems for the evaluation of teacher performance fits into the search for solutions to that concern. This is what happened in Portugal, in January 2007, when the new Statute of the Teaching Profession and the law to regulate Teacher Performance Assessment were published in Diário da República – the official government publication. Tensions arose between teachers and the Ministry of Education and they were aggravated by an awareness of how the problem of teacher performance evaluation would impact on the professional career of teachers and how it would cause uncertainties and demotivation concerning the vocation of teaching and its subsequent impact on the professional identity of teachers