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Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in BReast CAncer (BRCA) genes are responsible for the majority of cases of hereditary breast and ovarian cancer. BRCA1 and BRCA2 act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination. Evidence of the accumulation of DNA double-strand break has been reported in aging oocytes, while BRCA expression decreases, leading to the hypothesis that BRCA mutation may impact fertility. Moreover, patients exposed to anticancer treatments are at higher risk of fertility-related issues, and BRCA mutations could exacerbate the treatment-induced depletion of the ovarian reserve. In this review, we summarized the functions of both genes and reported the current knowledge on the impact of BRCA mutations on ovarian ageing, premature ovarian insufficiency, female fertility preservation strategies and insights about male infertility. Altogether, this review provides relevant up-to-date information on the impact of BRCA1/2 mutations on fertility. Notably, BRCA-mutated patients should be adequately counselled for fertility preservation strategies, considering their higher sensitivity to chemotherapy gonadotoxic effects.

The Hippo pathway plays a crucial role in the regulation of follicular activation, which constitutes the first step of the folliculogenesis process. Disruption of this pathway occurs in several non-physiological contexts, after fragmentation for ovarian tissue cryopreservation procedures or chemotherapy exposure, leading to massive follicular growth and depletion. This study aimed to investigate the effect of controlling the Hippo pathway using verteporfin (VERT) during in vitro ovarian culture and to evaluate its potential preventive effects on chemotherapy-induced follicle activation using a mouse model. After exposure of cut ovaries to different concentrations of VERT for 3 h, a dose-dependent effect of VERT was observed that reached significant inhibition of YAP activity at 3 µmol/L. To assess the potential effect of controlling chemotherapy-induced Hippo pathway disruption, whole mouse ovaries were exposed to VERT alone or as a co-treatment with 4-hydroperoxycylophosphamide (4HC). VERT co-treatment prevented chemotherapy-induced YAP activation but had a limited impact on downstream effector gene, Ccn2 . Surprisingly, VERT co-treatment also prevented mTOR and survival signaling pathway alterations following chemotherapy exposure. These results suggest an interaction between the two main signaling pathways regulating follicle activation and a protective effect of VERT on 4HC-induced DNA damage.

β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. β-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of β-glucans are deeply influenced by their molecular structure. This structure governs β-glucan interaction with multiple β-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of β-glucans to fully reveal their biological roles and potential applications. The deconstruction of β-glucans is a result of β-glucanase activity. In addition to being invaluable tools for the study of β-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for β-glucans and β-glucanases, and explore how their functionalities are dictated by their structure.

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasiveness, and are therefore key determinants of disease progression, with a strong influence in patient prognosis and response to therapy. Due to their multifaceted role in the tumor immune response and tumor biology, the chemokine network has emerged as a potential immunotherapy target. Under the present review, we provide a general overview of chemokine effects on several tumoral processes, as well as a description of the currently available chemokine-directed therapies, highlighting their potential both as monotherapy or in combination with standard chemotherapy or other immunotherapies. Finally, we discuss the most critical challenges and prospects of developing targeted chemokines as therapeutic options.

Introdução:o mestrado em Enfermagem de Saúde Materna e Obstétrica pressupõe a realização de um estágio de natureza profissional com relatório final, para obtenção de grau de mestre e título de Enfermeiro Especialista.Objetivos:demonstrar crítica e reflexivamente a aquisição de competências comuns e específicas no decurso do referido estágio.Metodologia:estágio sob supervisão, em diversos contextos clínicos, desenvolvendo o raciocínio clínico, apoiado numa revisão da literatura, dando assim construto para uma prática baseada na evidência, aliando a recolha de informação, em contexto clínico, sobre a temática que dá tema ao presente relatório.Resultados:adquiriu-se e desenvolveu-se diversas competências comuns e específicas de enfermeiro especialista, conseguindo ainda aferir a relevância do sono durante a gravidez, contribuindo assim para a aquisição de competências na temática.Conclusão:este estágio relevou-se uma mais-valia para a aquisição das referidas competências, não esquecendo a relevância do sono durante a gravidez, contribuindo para a tomada de decisão baseada na evidência científica.

Non-Hodgkin lymphoma (NHL) is one of the most common causes of cancer-related death worldwide. Although the outcome of NHL patients has improved with current therapies, the rate of mortality is still high. A plethora of new drugs is entering clinical development for NHL treatment; however, the approval of new treatments remains low due in part to the paucity of clinically relevant models for validation. Canine lymphoma (cNHL) shares remarkable similarities with its human counterpart, making the dog an excellent animal model to explore novel therapeutic options. Therefore, driven by the great success achieved by immunotherapies in human NHL, comparative research has focused on the development of similar immunotherapeutic approaches for dogs. However, the successful use of this animal model remains challenging, still lacking the characterization of the canine immune system, of common tumor epitopes, the development of canine-specific/cross-reactive agents and the establishment of preclinical models. Within this context, we aimed to develop novel antibody-based therapies for cNHL, while contributing for the characterization and validation of the cNHL model for translational immune-oncology research. For that purpose, a cNHL biobank was successfully constructed. The clinical cytokine patterns in patients with cNHL were investigated, confirming a local and systemic dysregulation in cytokine response. Furthermore, a positive correlation between intratumoral immune response and a favorable response to chemotherapy indicates that the modulation of the immune response might contribute to improve patient outcomes. With that in mind, a through characterization of canine CD20 expression was conducted and contributed for the validation of this receptor as a potential immunotherapeutic target for cNHL. This motivated the development and identification of a panel of single domain antibodies (sdAbs) with high binding activity and specificity to canine and human CD20. In addition, to develop a novel drug delivery system for cNHL treatment, we described novel methodologies to identify potential targets, while selecting highly specific sdAbs against NHL. This work allowed to select a promising pool of sdAbs that specifically target NHL tumor receptors for the development of a novel antibody drug conjugate (ADC). Furthermore, we conducted a thorough investigation of a novel ADC payload – panobinostat - a potent histone deacetylase (HDAC) inhibitor with strong in vitro and in vivo antitumor properties in cNHL. Finally, we established a new bioluminescent murine model for monitoring tumor progression and treatment response in preclinical studies. In summary, the work presented herein allowed the establishment of a solid platform for the acceleration of the translational research of novel immunotherapeutic approaches for comparative oncology.

O diagnóstico preciso e precoce de metástases pulmonares apresenta repercussões importantes no prognóstico a curto e a longo prazo, no estadiamento, na terapêutica médica, tanto do tumor primário como das metástases e no planeamento cirúrgico. O presente estudo retrospectivo teve como objectivos a comparação do diagnóstico imagiológico de metastização pulmonar através de radiologia e da tomografia computorizada, bem como a descrição e caracterização dos sinais imagiológicos das lesões compatíveis com metástases pulmonares. Foram incluídos neste estudo 27 cães mediante a confirmação de doença oncológica com possibilidade de metastização pulmonar. Os animais foram submetidos a um estudo radiográfico com um protocolo de, no mínimo, duas projecções e a um estudo por tomografia computorizada. Os sinais imagiológicos foram então descritos e caracterizados para efeitos de análise. O estudo tomográfico permitiu a detecção de lesões nodulares, compatíveis com metástases pulmonares, em 22,2% dos casos, enquanto as radiografias torácicas demonstraram evidências de metastização em 7,4%. Os resultados deste estudo sugerem que o exame tomográfico apresenta maior sensibilidade na detecção de metastização pulmonar, em comparação com a radiografia. Por um lado, melhora a avaliação das lesões metastáticas, relativamente ao número, localização anatómica e relação com as estruturas envolventes, dimensão e características morfológicas. Por outro lado, é superior na detecção do envolvimento dos linfonodos intratorácicos. Concluiu-se que a TC deve ser realizada em associação com o estudo radiográfico, na pesquisa de metástases pulmonares, em doentes oncológicos com risco de desenvolverem doença metastática pulmonar

O diagnóstico preciso e precoce de metástases pulmonares apresenta repercussões importantes no prognóstico a curto e a longo prazo, no estadiamento, na terapêutica médica, tanto do tumor primário como das metástases e no planeamento cirúrgico.O presente estudo retrospectivo teve como objectivos a comparação do diagnóstico imagiológico de metastização pulmonar através de radiologia e da tomografia computorizada, bem como a descrição e caracterização dos sinais imagiológicos das lesões compatíveis com metástases pulmonares.Foram incluídos neste estudo 27 cães mediante a confirmação de doença oncológica com possibilidade de metastização pulmonar. Os animais foram submetidos a um estudo radiográfico com um protocolo de, no mínimo, duas projecções e a um estudo por tomografia computorizada. Os sinais imagiológicos foram então descritos e caracterizados para efeitos de análise.O estudo tomográfico permitiu a detecção de lesões nodulares, compatíveis com metástases pulmonares, em 22,2% dos casos, enquanto as radiografias torácicas demonstraram evidências de metastização em 7,4%.Os resultados deste estudo sugerem que o exame tomográfico apresenta maior sensibilidade na detecção de metastização pulmonar, em comparação com a radiografia. Por um lado, melhora a avaliação das lesões metastáticas, relativamente ao número, localização anatómica e relação com as estruturas envolventes, dimensão e características morfológicas. Por outro lado, é superior na detecção do envolvimento dos linfonodos intratorácicos.Concluiu-se que a TC deve ser realizada em associação com o estudo radiográfico, na pesquisa de metástases pulmonares, em doentes oncológicos com risco de desenvolverem doença metastática pulmonar.

Abstract Background The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed. Methods This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation). Results Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04). Conclusions The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.

Acacia longifolia is one of the most aggressive invaders worldwide whose invasion is potentiated after a fire, a common perturbation in Mediterranean climates. As a legume, this species establishes symbioses with nitrogen-fixing bacteria inside root nodules; however, the overall microbial diversity is still unclear. In this study, we addressed root nodules’ structure and biodiversity through histology and Next-Generation Sequencing, targeting 16S and 25S-28S rDNA genes for bacteria and fungi, respectively. We wanted to evaluate the effect of fire in root nodules from 1-year-old saplings, by comparing unburnt and burnt sites. We found that although having the same general structure, after a fire event, nodules had a higher number of infected cells and greater starch accumulation. Starch accumulated in uninfected cells can be a possible carbon source for the microbiota. Regarding diversity, Bradyrhizobium was dominant in both sites (ca. 77%), suggesting it is the preferential partner, followed by Tardiphaga (ca. 9%), a non-rhizobial Alphaproteobacteria, and Synechococcus, a cyanobacteria (ca. 5%). However, at the burnt site, additional N-fixing bacteria were included in the top 10 genera, highlighting the importance of this process. Major differences were found in the mycobiome, which was diverse in both sites and included genera mostly described as plant endophytes. Coniochaeta was dominant in nodules from the burnt site (69%), suggesting its role as a facilitator of symbiotic associations. We highlight the presence of a large bacterial and fungal community in nodules, suggesting nodulation is not restricted to nitrogen fixation. Thus, this microbiome can be involved in facilitating A. longifolia invasive success.