Search Results (17)

Ovarian cancer poses a significant threat to patients in its advanced stages, often with limited treatment options available. In such cases, palliative management becomes the primary approach to maintaining a reasonable quality of life. Therefore, the administration of any medication that can benefit patients without a curative option holds potential. Resveratrol, a natural compound known for its in vitro anticancer activities, has generated contrasting results in vivo and human studies. In this study, we aimed to assess the anticancer effects of resveratrol on ovarian cancer cells grown on the chorioallantoic membrane (CAM) of chicken embryos. Two ovarian cancer cell lines, OVCAR-8 and SKOV-3, were cultured in collagen scaffolds for four days before being implanted on the CAM of chicken embryos on day 7. Different doses of resveratrol were applied to the CAM every two days for six days. Subsequently, CAM tissues were excised, fixed, and subjected to histological analysis. Some CAM tumours were extracted to analyse proteins through Western blotting. Our findings indicate that specific doses of resveratrol significantly reduce angiogenic activities, pNF-κB levels, and SLUG protein levels by using immunohistochemistry. These results suggest that resveratrol may have the potential to impact the behaviour of ovarian cancer CAM tumours, thereby warranting further consideration as a complementary treatment option for women with incurable ovarian cancer. Full article

Breast cancer (BC) remains the most common cancer among women worldwide, and estrogen receptor-α expression is a critical diagnostic factor for BC. Estrogen receptor (ER-α36) is a dominant-negative effector of ER-α66-mediated estrogen-responsive gene pathways. ER-α36 is a novel target that mediates the non-genomic estrogen signaling pathway. However, the crystallized structure of ER-α36 remains unavailable for molecular studies. ER-positive and triple-negative BC tumors aggressively resist the FDA-approved drugs; therefore, highly potent structure-based inhibitors with preeminent benefits over toxicity will preferably replace the current BC treatment. Broussoflanol B (BFB), a B. papyrifera bark compound, exhibits potent growth inhibitory activity in ER-negative BC cells by inducing cell cycle arrest. For the first time, we unravel the comparative dynamic events of the enzymes’ structures and the binding mechanisms of BFB when bound to the ER-α36 and ER-α66 ligand-binding domain using an all-atom molecular dynamics simulations approach and MM/PBSA-binding-free energy calculations. The dynamic findings have revealed that ER-α36 and ER-α66 LBD undergo timescale “coiling”, opening and closing conformations favoring the high-affinity BFB-bound ER-α36 (ΔG = −52.57 kcal/mol) compared to the BFB-bound ER-α66 (ΔG = −42.41 kcal/mol). Moreover, the unbound (1.260 Å) and bound ER-α36 (1.182 Å) exhibit the highest flexibilities and atomistic motions relative to the ER-α66 systems. The RMSF (Å) of the unbound ER-α36 and ER-α66 exhibit lesser stabilities than the BFB-bound systems, resulting in higher structural flexibilities and atomistic motions than the bound variants. These findings present a model that describes the mechanisms by which the BFB compound induces downregulation-accompanied cell cycle arrest at the Gap₀ and Gap₁ phases. Full article

Despite recent progressions in cancer genomic and immunotherapies, advanced melanoma still represents a life threat, pushing to optimise new targeted nanotechnology approaches for specific drug delivery to the tumour. To this aim, owing to their biocompatibility and favourable technological features, injectable lipid nanoemulsions were functionalised with proteins owing to two alternative approaches: transferrin was chemically grafted for active targeting, while cancer cell membrane fragments wrapping was used for homotypic targeting. In both cases, protein functionalisation was successfully achieved. Targeting efficiency was preliminarily evaluated using flow cytometry internalisation studies in two-dimensional cellular models, after fluorescence labelling of formulations with 6-coumarin. The uptake of cell-membrane-fragment-wrapped nanoemulsions was higher compared to uncoated nanoemulsions. Instead, the effect of transferrin grafting was less evident in serum-enriched medium, since such ligand probably undergoes competition with the endogenous protein. Moreover, a more pronounced internalisation was achieved when a pegylated heterodimer was employed for conjugation (p < 0.05). Full article

Background: In Spain, people who have overcome some type of cancer have significantly worse self-perceived health (SPH) and higher rates of depression than people who have never suffered any type of cancer. Objective: to explore the relationships among physical activity levels (PAL), perceived social support (PSS), and SPH in terms of mental health and its dimensions in Spanish adults with cancerous tumours. Methods: A correlational study rooted in the National Health Survey 2017 for adults was carried out, including 627 Spanish residents who reported having malignant tumours. Results: A dependent association was found between PAL and SPH (p < 0.001). The mental health mean score decreased as PAL increased for the total sample and for both sexes, separately (p < 0.001). Low reverse associations were also observed between PAL and mental health (rho: −0.274; p < 0.001), successful coping (rho: −0.239; p < 0.001) and self-confidence (rho: −0.264; p <0.001). Moreover, PSS weakly and inversely correlates with mental health (r: −0.225; p < 0.001), successful coping (r: −0.218; p < 0.001) and self-confidence (r: −0.231; p < 0.001). A binary logistic model showed that active and very active people presented less threat of poor SPH, as did people with higher PSS (p < 0.001). Conclusions: Greater levels of physical activity are associated with larger mean scores in the three dimensions of mental health, perceived social support and self-perceived health in people with cancerous tumours. Full article

Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type. Full article

Cutaneous fibropapillomatosis, first reported in green turtles (Chelona mydas) in 1930, is considered a global epizootic that affects up to 97% of sea turtles, with major consequences for threatened populations. Although this is a benign tumour that arises on the skin or internal organs, it can have serious and potentially fatal consequences when it compromises critical functions such as swimming, feeding, or breathing. The aetiology of this tumour is not yet well defined, but it has been primarily associated with Chelonide herpesvirus 5. Some studies also highlight exogenous environmental factors such as water temperature and pollutants, which may have caused a host-virus–host imbalance and the onset of the disease. Climate change seems to have a role in the dissemination of this pathology among sea turtle populations. Although not fully understood, the relationship between fibropapilomatosis and the state of environmental health is well recognized. Further research is needed to better understand this disease, which silently devastates entire populations of marine turtles. Daily human activities may have a greater impact on wildlife populations than can be expected. There is an urgent need to reverse human threats to wildlife. Full article

Cancer remains one of the diseases with the highest worldwide incidence. Several cytotoxic approaches have been used over the years to overcome this public health threat, such as chemotherapy, radiotherapy, and photodynamic therapy (PDT). Cyanine dyes are a class of compounds that have been extensively studied as PDT sensitisers; nevertheless, their antiproliferative potential in the absence of a light source has been scarcely explored. Herein, the synthesis of eighteen symmetric mono-, tri-, and heptamethine cyanine dyes and their evaluation as potential anticancer agents is described. The influences of the heterocyclic nature, counterion, and methine chain length on the antiproliferative effects and selectivities were analysed, and relevant structure–activity relationship data were gathered. The impact of light on the cytotoxic activity of the most promising dye was also assessed and discussed. Most of the monomethine and trimethine cyanine dyes under study demonstrated a high antiproliferative effect on human tumour cell lines of colorectal (Caco-2), breast (MCF-7), and prostate (PC-3) cancer at the initial screening (10 µM). However, concentration–viability curves showed higher potency and selectivity for the Caco-2 cell line. A monomethine cyanine dye derived from benzoxazole was the most promising compound (IC₅₀ for Caco-2 = 0.67 µM and a selectivity index of 20.9 for Caco-2 versus normal human dermal fibroblasts (NHDF)) and led to Caco-2 cell cycle arrest at the G0/G1 phase. Complementary in silico studies predicted good intestinal absorption and oral bioavailability for this cyanine dye. Full article

Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed. Full article

Oncological surgery, obstetric haemorrhage and severe trauma are the most challenging conditions for establishing clinical recommendations for the use of cell salvage. When the likelihood of allogeneic transfusion is high, the intraoperative use of this blood-saving technique would be justified, but specific patient selection criteria are needed. The main concerns in the case of oncological surgery are the reinfusion of tumour cells, thereby increasing the risk of metastasis. This threat could be minimized, which may help to rationalize its indication. In severe peripartum haemorrhage, cell salvage has not proven cost-effective, damage control techniques have been developed, and, given the risk of fetomaternal alloimmunization and amniotic fluid embolism, it is increasingly out of use. In trauma, bleeding may originate from multiple sites, coagulopathy may develop, and it should be evaluated whether re-transfusion of autologous blood collected from uncontaminated organ cavities would be feasible. General safety measures include washing recovered blood and its passage through leukocyte depletion filters. To date, no well-defined indications for cell salvage have been established for these pathologies, but with accurate case selection and selective implementation, it could become safe and effective. Randomized clinical trials are urgently needed. Full article

Background: Oral cancer (OC) is a common tumour that poses a threat to human health and imposes a heavy burden on countries. This study assessed the burden imposed by OC on the 10 most populous countries from 1990 to 2019 on the basis of gender, age and socio-demographic index. Methods: Data on incidence, mortality, disability-adjusted life years (DALY) and corresponding age-standardised rates (ASR) for OC in the 10 most populous countries from 1990 to 2019 were derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes were calculated to assess the trends of morbidity, mortality and DALY. The indicator that served as a proxy for survival rate was the supplement of mortality-to-incidence ratio (SMIR) (1 − (M/I)). Results: The number of new cases, deaths and DALY have increased in all 10 countries in the past 30 years. Trends in age-standardised incidence rates (ASIR), age-standardised mortality rate (ASMR) and age-standardised DALY for OC in the 10 most populous countries varied. The SMIR increased in all countries, with most countries having an SMIR between 30% and 50%. In 2019, the United States had the highest SMIR at 76%, whereas Russia had the lowest at 21.7%. Incidence and mortality were close between male and female subjects in Japan, Indonesia, Mexico, India, Bangladesh and Pakistan. The incidence and mortality in male subjects in the United States, Russia, China and Brazil were two or more times those of female subjects. Gender difference was highest among patients aged 40–69 years. Conclusion: Trends and gender differences in ASIR, ASMR and age-standardised DALY for OC vary in the 10 most populous countries. Government cancer programs are often expensive to run, especially in countries with large populations. Policy makers need to take these differences into account when formulating policies. Full article

Fibropapillomatosis (FP) of sea turtles is characterised by cutaneous tumours and is associated with Chelonid herpesvirus 5 (ChHV5), an alphaherpesvirus from the family Herpesviridae. Here, we provide the first evidence of ChHV5-associated FP in endangered Green turtles (Chelonia mydas) from Sabah, which is located at the northern region of Malaysian Borneo. The aims of our study were firstly, to determine the presence of ChHV5 in both tumour exhibiting and tumour-free turtles using molecular techniques and secondly, to determine the phylogeography of ChHV5 in Sabah. We also aim to provide evidence of ChHV5 infection through histopathological examinations. A total of 115 Green turtles were sampled from Mabul Island, Sabah. We observed three Green turtles that exhibited FP tumours and were positive for ChHV5. In addition, six clinically healthy turtles (with no presence of tumours) were also positive for the virus based on Polymerase Chain Reaction of three viral genes (Capsid protein gene UL18, Glycoprotein H gene UL22, and Glycoprotein B gene UL27). The prevalence of the ChHV5 was 5.22% in asymptomatic Green turtles. Epidermal intranuclear inclusions were identified in tumour lesions upon histopathological examination. In addition, phylogenetic analyses of the UL18, UL22, UL27, and UL30 gene sequences showed a worldwide distribution of the ChHV5 strain with no clear distinction based on geographical location suggesting an interoceanic connection and movement of the sea turtles. Thus, the emergence of ChHV5 in Green turtles in the waters of Sabah could indicate a possible threat to sea turtle populations in the future and requires further monitoring of the populations along the Bornean coast. Full article

The spreading global sea turtle fibropapillomatosis (FP) epizootic is threatening some of Earth’s ancient reptiles, adding to the plethora of threats faced by these keystone species. Understanding this neoplastic disease and its likely aetiological pathogen, chelonid alphaherpesvirus 5 (ChHV5), is crucial to understand how the disease impacts sea turtle populations and species and the future trajectory of disease incidence. We generated 20 ChHV5 genomes, from three sea turtle species, to better understand the viral variant diversity and gene evolution of this oncogenic virus. We revealed previously underappreciated genetic diversity within this virus (with an average of 2035 single nucleotide polymorphisms (SNPs), 1.54% of the ChHV5 genome) and identified genes under the strongest evolutionary pressure. Furthermore, we investigated the phylogeny of ChHV5 at both genome and gene level, confirming the propensity of the virus to be interspecific, with related variants able to infect multiple sea turtle species. Finally, we revealed unexpected intra-host diversity, with up to 0.15% of the viral genome varying between ChHV5 genomes isolated from different tumours concurrently arising within the same individual. These findings offer important insights into ChHV5 biology and provide genomic resources for this oncogenic virus. Full article

Reactive oxygen species (ROS) play an important role in cell proliferation and differentiation. They are also by-products of aerobic living conditions. Their inherent reactivity poses a threat for all cellular components. Cells have, therefore, evolved complex pathways to sense and maintain the redox balance. Among them, Nrf2 (Nuclear factor erythroid 2-related factor 2) plays a crucial role: it is activated under oxidative conditions and is responsible for the expression of the detoxification machinery and antiapoptotic factors. It is, however, a double edge sword: whilst it prevents tumorigenesis in healthy cells, its constitutive activation in cancer promotes tumour growth and metastasis. In addition, recent data have highlighted the importance of Nrf2 in evading programmed cell death. In this review, we will focus on the activation of the Nrf2 pathway in the cytoplasm, the molecular basis underlying Nrf2 binding to the DNA, and the dysregulation of this pathway in cancer, before discussing how Nrf2 contributes to the prevention of apoptosis and ferroptosis in cancer and how it is likely to be linked to detoxifying enzymes containing selenium. Full article

Extinction risk is increasing for a range of species due to a variety of threats, including disease. Emerging infectious diseases can cause severe declines in wild animal populations, increasing population fragmentation and reducing gene flow. Small, isolated, host populations may lose adaptive potential and become more susceptible to extinction due to other threats. Management of the genetic consequences of disease-induced population decline is often necessary. Whilst disease threats need to be addressed, they can be difficult to mitigate. Actions implemented to conserve the Tasmanian devil (Sarcophilus harrisii), which has suffered decline to the deadly devil facial tumour disease (DFTD), exemplify how genetic management can be used to reduce extinction risk in populations threatened by disease. Supplementation is an emerging conservation technique that may benefit populations threatened by disease by enabling gene flow and conserving their adaptive potential through genetic restoration. Other candidate species may benefit from genetic management via supplementation but concerns regarding outbreeding depression may prevent widespread incorporation of this technique into wildlife disease management. However, existing knowledge can be used to identify populations that would benefit from supplementation where risk of outbreeding depression is low. For populations threatened by disease and, in situations where disease eradication is not an option, wildlife managers should consider genetic management to buffer the host species against inbreeding and loss of genetic diversity. Full article

The impact of emerging infectious diseases is increasingly recognised as a major threat to wildlife. Wild populations of the endangered Tasmanian devil, Sarcophilus harrisii, are experiencing devastating losses from a novel transmissible cancer, devil facial tumour disease (DFTD); however, despite the rapid decline of this species, there is currently no information on the presence of haemoprotozoan parasites. In the present study, 95 Tasmanian devil blood samples were collected from four populations in Tasmania, Australia, which underwent molecular screening to detect four major groups of haemoprotozoa: (i) trypanosomes, (ii) piroplasms, (iii) Hepatozoon, and (iv) haemosporidia. Sequence results revealed Trypanosoma infections in 32/95 individuals. Trypanosoma copemani was identified in 10 Tasmanian devils from three sites and a second Trypanosoma sp. was identified in 22 individuals that were grouped within the poorly described T. cyclops clade. A single blood sample was positive for Babesia sp., which most closely matched Babesia lohae. No other blood protozoan parasite DNA was detected. This study provides the first insight into haemoprotozoa from the Tasmanian devil and the first identification of Trypanosoma and Babesia in this carnivorous marsupial. Full article