Search Results (141)

After birth, the immune system is challenged by numerous elements of the extrauterine environment, reflected in fluctuations of inflammatory markers. The concentrations of these markers in the first month of life are associated with the future performance of dairy youngstock. It is thought that bacterial genera colonizing the calf intestinal tract can cause inflammation and thus affect their host’s performance via immunomodulation. This study explored how the faecal microbiota of newborn dairy calves were related to inflammatory markers during the first three weeks of life, and if the abundance of specific genera was associated with first-lactation performance. Ninety-five female Holstein calves were studied. Once a week, serum and faecal samples were collected, serum concentrations of serum amyloid A, haptoglobin, tumour necrosis factor-α, and interleukin-6 were measured, and faecal microbiota composition was examined by 16S rRNA gene amplicon sequencing. Faecal Gallibacterium abundance in the first week of age and Collinsella abundance in the second week were negatively associated with inflammatory response as well as with calving–conception interval. Peptostreptococcus abundance in the second week of life was positively associated with inflammatory response and calving–conception interval, and negatively with average daily weight gain. In the third week, Dorea abundance was positively, Bilophila abundance was negatively associated with inflammatory response, and both genera were negatively associated with age at first calving. These bacterial genera may be able to influence the inflammatory response and through this, possibly the future performance of the dairy heifer. Deciphering such microbiota–host interactions can help improve calf management to benefit production and welfare. Full article

Carotenoids, known for their antioxidant properties, have garnered significant attention for their potential antitumour activities. This comprehensive review aims to elucidate the diverse mechanisms by which carotenoids exert antitumour effects, focusing on both well-established and novel findings. We explore their role in inducing apoptosis, inhibiting cell cycle progression and preventing metastasis by affecting oncogenic and tumour suppressor proteins. The review also explores the pro-oxidant function of carotenoids within cancer cells. In fact, although their overall contribution to cellular antioxidant defences is well known and significant, some carotenoids can exhibit pro-oxidant effects under certain conditions and are able to elevate reactive oxygen species (ROS) levels in tumoural cells, triggering mitochondrial pathways that would lead to cell death. The final balance between their antioxidant and pro-oxidant activities depends on several factors, including the specific carotenoid, its concentration and the redox environment of the cell. Clinical trials are discussed, highlighting the conflicting results of carotenoids in cancer treatment and the importance of personalized approaches. Emerging research on rare carotenoids like bacterioruberin showcases their superior antioxidant capacity and selective cytotoxicity against aggressive cancer subtypes, such as triple-negative breast cancer. Future directions include innovative delivery systems, novel combinations and personalized treatments, aiming to enhance the therapeutic potential of carotenoids. This review highlights the promising yet complex landscape of carotenoid-based cancer therapies, calling for continued research and clinical exploration. Full article

The search for new antineoplastic agents is imperative, as cancer remains one of the most preeminent causes of death worldwide. Since the discovery of the therapeutic potential of cisplatin, the study of metallodrugs in cancer chemotherapy acquired increasing interest. Starting from cisplatin derivatives, such as oxaliplatin and carboplatin, in the last years, different compounds were explored, employing different metal centers such as iron, ruthenium, gold, and palladium. Nonetheless, metallodrugs face several drawbacks, such as low water solubility, rapid clearance, and possible side toxicity. Encapsulation has emerged as a promising strategy to overcome these issues, providing both improved biocompatibility and protection of the payload from possible degradation in the biological environment. In this respect, liposomes, which are spherical vesicles characterized by an aqueous core surrounded by lipid bilayers, have proven to be ideal candidates due to their versatility. In fact, they can encapsulate both hydrophilic and hydrophobic drugs, are biocompatible, and their properties can be tuned to improve the selective delivery to tumour sites exploiting both passive and active targeting. In this review, we report the most recent findings on liposomal formulations of metallodrugs, with a focus on encapsulation techniques and the obtained biological results. Full article

Brain tumour disease develops due to abnormal cell proliferation. The early identification of brain tumours is vital for their effective treatment. Most currently available examination methods are laborious, require extensive manual instructions, and produce subpar findings. The EfficientNet-B0 architecture was used to diagnose brain tumours using magnetic resonance imaging (MRI). The fine-tuned EffeceintNet B0 model was proposed for the Internet of Medical Things (IoMT) environment. The fine-tuned EfficientNet-B0 architecture was employed to classify four different stages of brain tumours from the MRI images. The fine-tuned model showed 99% accuracy in the detection of four different classes of brain tumour detection (glioma, no tumour, meningioma, and pituitary). The proposed model performed very well in the detection of the pituitary class with a precision of 0.95, recall of 0.98, and F1 score of 0.96. The proposed model also performed very well in the detection of the no-tumour class with values of 0.99, 0.90, and 0.94 for precision, recall, and the F1 score, respectively. The precision, recall, and F1 scores for Glioma and Meningioma classes were also high. The proposed solution has several implications for enhancing clinical investigations of brain tumours. Full article

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. Full article

Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and inflammatory exposure. Physical activity offers protection against breast cancer by modulating hormones, immune responses, and oxidative defenses. This study aimed to assess how a prolonged high-fat diet (HFD) affects the effectiveness of physical activity in preventing and managing mammary tumorigenesis. Ovariectomised C57BL/6 mice were provided with an enriched environment to induce spontaneous physical activity while being fed HFD. After 44 days (short-term, ST HFD) or 88 days (long-term, LT HFD), syngenic EO771 cells were implanted into mammary glands, and tumour growth was monitored until sacrifice. Despite similar physical activity and food intake, the LT HFD group exhibited higher visceral adipose tissue mass and reduced skeletal muscle mass. In the tumour microenvironment, the LT HFD group showed decreased NK cells and TCD8+ cells, with a trend toward increased T regulatory cells, leading to a collapse of the T8/Treg ratio. Additionally, the LT HFD group displayed decreased tumour triglyceride content and altered enzyme activities indicative of oxidative stress. Prolonged exposure to HFD was associated with tumour growth despite elevated physical activity, promoting a tolerogenic tumour microenvironment. Future studies should explore inter-organ exchanges between tumour and tissues. Full article

Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases. Full article

FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin. Full article

Cell cultivation has been one of the most popular methods in research for decades. Currently, scientists routinely use two-dimensional (2D) and three-dimensional (3D) cell cultures of commercially available cell lines and primary cultures to study cellular behaviour, responses to stimuli, and interactions with their environment in a controlled laboratory setting. In recent years, 3D cultivation has gained more attention in modern biomedical research, mainly due to its numerous advantages compared to 2D cultures. One of the main goals where 3D culture models are used is the investigation of tumour diseases, in both animals and humans. The ability to simulate the tumour microenvironment and design 3D masses allows us to monitor all the processes that take place in tumour tissue created not only from cell lines but directly from the patient’s tumour cells. One of the tumour types for which 3D culture methods are often used in research is the canine mammary gland tumour (CMT). The clinically similar profile of the CMT and breast tumours in humans makes the CMT a suitable model for studying the issue not only in animals but also in women. Full article

The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international consensus and guidelines in the field recommend that patients with pituitary tumours should always be managed in a MDT. Endocrinologists and neurosurgeons are normally the leading specialties within the pituitary MDT, supported by many other specialties with significant contributions to the diagnosis and management of pituitary tumours, including neuropathology, neuroradiology, neuro-ophthalmology, and otorhinolaryngology, among others. Here, we review the literature concerning the concepts of Pituitary MDT/Pituitary Tumour Centre of Excellence (PTCOE) in terms of their mission, goals, benefits, structure, proposed models of function, and barriers, and we also provide the views of different specialists involved in our Pituitary MDT. Full article

The tumour microenvironment (TME) is a complex and constantly evolving collection of cells and extracellular components. Cancer cells and the surrounding environment influence each other through different types of processes. Characteristics of the TME include abnormal vasculature, altered extracellular matrix, cancer-associated fibroblast and macrophages, immune cells, and secreted factors. Within these components, several molecules and pathways are altered and take part in the support of the tumour. Epigenetic regulation, kinases, phosphatases, metabolic regulators, and hormones are some of the players that influence and contribute to shaping the tumour and the TME. All these characteristics contribute significantly to cancer progression, metastasis, and immune escape, and may be the target for new approaches for cancer treatment. Full article

Cancer is widely regarded as a critical health issue in modern society. Tumour cells are usually associated with abnormal proliferation that disrupts the normal behaviour of the body. All cells depend on the availability of oxygen and nutrients present in the extracellular environment, which can enhance or decrease their ability to proliferate. Therefore, to comprehend the influence of these factors, it is helpful to understand the proliferation process of both healthy and tumour cells. Computational models are powerful tools used to study biomedical problems, and several models have been presented in the literature. Different numerical methods have been proposed to solve these models. Among them, meshless methods can be highlighted, as they are used to solve complex problems with accurate results. However, in the case of cell proliferation, this is still an area that has not yet been fully explored. The aim of this work is to implement and study the influence of oxygen and glucose during the proliferation of healthy and tumour cells using a novel algorithm. This is an iterative discrete algorithm that employs a meshless numerical and uses a new phenomenological law to describe cell growth. In the end, the algorithm was capable of generating satisfactory results, in accordance with the literature. Full article

Despite substantial progress in the diagnostic and therapeutic procedures, acute myeloid leukaemia (AML) still constitutes a significant problem for patients suffering from its relapses. A comprehensive knowledge of the disease’s molecular background has led to the development of targeted therapies, including immune checkpoint inhibitors, and demonstrated beneficial effects on several types of cancer. Here, we aimed to assess in vitro the potential of the immune checkpoint blockage for supporting anti-cancer responses to the AML backbone therapy with cytarabine. PBMCs of AML patients were collected at admission and, following the therapy, eight complete remission (CR) and eight non-responders (NR) subjects were selected. We assessed the effects of the in vitro treatment of the cells with cytarabine and the immune checkpoint inhibitors: anti-CTLA-4, anti-PD-1, anti-PD-L1. The study protocol allowed us to evaluate the viability of the cancer and the immune cells, proliferation status, phenotype, and cytokine release. Anti-PD-L1 antibodies were found to exert the most beneficial effect on the activation of T cells, with a concomitant regulation of the immune balance through Treg induction. There was no direct influence on the blast cells; however, the modulation of the PD-1/PD-L1 axis supported the expansion of lymphocytes. Changes in the response between CR and NR patients might result from the differential expression of PD-1 and PD-L1, with lower levels in the latter group. The tested blockers appear to support the anti-cancer immune responses rather than directly improve the effects of cytarabine. In conclusion, checkpoint proteins’ modulators might improve the anti-cancer responses in the tumour environment. Full article

Endotoxin tolerance (ET) is an adaptive phenomenon of the immune system that protects the host from clinical complications due to repeated exposure of the body to endotoxins such as lipopolysaccharide (LPS). Since ET is an immunosuppressive mechanism in which a significant reprogramming of macrophages is observed, we hypothesized that it could influence cancer development by modifying the tumour environment. This study aimed to explore whether ET influences cancer progression by altering the tumour microenvironment. Endotoxin-tolerant macrophages (Mo_ET) were examined for their impact on breast and colon cancer cells via direct interaction and conditioned media exposure. We characterized cancer cell behaviour by viability, clonogenic potential, motility, scratch assays, and 3D spheroidal assays. Mo_ET-derived factors increased cancer cell viability, motility, and clonogenicity, suggesting a conducive environment for cancer development. Remarkably, despite reduced TNFα and IL-6 levels, Mo_ET exhibited M1 polarization. These findings uncover an ET-associated macrophage reprogramming that fosters a favourable context for cancer progression across diverse tumours. Targeting ET could emerge as a promising avenue for cancer therapy and prevention. Full article

Neuroblastoma, a paediatric malignancy of the peripheral nervous system, displays a wide range of clinical outcomes, including regression to fatality despite extensive treatment. Neuroblastoma tumours display a complex interplay with their surrounding environment, known as the tumour microenvironment, which may affect disease progression and patient prognosis. This study aimed to dissect the ways in which neuroblastoma biology, treatment, prognosis, progression, and relapse are linked with the extracellular matrix, the dichotomous identities of neuroblastoma, various regulatory proteins and RNA, and extracellular vesicles within the backdrop of the tumour microenvironment. In addition, other aspects, such as immune cell infiltration, therapeutic options including monoclonal antibodies and small molecule inhibitors; and the ways in which these may affect disease progression and immunosuppression within the context of the neuroblastoma tumour microenvironment, are addressed. Such studies may shed light on useful therapeutic targets within the tumour microenvironment that may benefit groups of NB patients. Ultimately, a detailed understanding of these aspects will enable the neuroblastoma scientific community to improve treatment options, patient outcomes, and quality of life. Full article