The Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin–ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype.
This systematic review aims to assess the genetic determinants influencing combat sports performance and address potential gaps in previous reviews. Twenty-four selected studies were analysed, investigating genetic influences on physiological performance, psychological traits, psychophysiological factors like pain perception, and injury susceptibility in combat sport athletes. The systematic literature search, using keywords, encompassed PubMed, Scopus, SportDiscus, Medline, and Google Scholar. The Covidence systematic review management software facilitated the screening process and the creation of the PRISMA flow diagram. The quality assessment complied with the PRISMA guidelines, featuring a custom 10-point scale and the STREGA criteria for more reliable study inclusion. Collectively, the 24 studies incorporated 18,989 participants, of which 3323 were combat athletes of majority European ancestry (71.7%) from various combat sports disciplines. Twenty-five unique genetic variants were significantly associated with combat sports performance across diverse domains. These included physiological performance (nine genetic variants), psychological traits (ten genetic variants), psychophysiological factors (one genetic variant), and injury susceptibility (four genetic variants). In conclusion, this systematic review lays the foundation for a more comprehensive exploration of the association between genetics and athletic performance in the demanding arena of combat sports, offering valuable insights for talent identification, training optimisation, and injury prevention.
Breast cancer is a persisting global burden for health services with cases and deaths projected to rise in future years. Surgery complemented by adjuvant therapy is commonly used to treat breast cancer, however comes with detrimental side effects to physical fitness and mental wellbeing. The aim of this systematic review and meta-analysis is to determine whether resistance and endurance interventions performed during adjuvant treatment can lastingly ameliorate these side effects. A systematic literature search was performed in various electronic databases. Papers were assessed for bias and grouped based on intervention design. RStudio was used to perform the meta-analyses for each group using the ‘meta’ package. Publication bias and power analyses were also conducted. These methods conform to PRISMA guidelines. Combined resistance and endurance interventions elicited significant long-lasting improvements in global fatigue and were beneficial to the remaining side effects. Individually, resistance and endurance interventions non-significantly improved these side effects. Resistance interventions elicited higher benefits overall. Exercise interventions have lasting clinical benefits in ameliorating adjuvant therapy side effects, which negatively impact physical fitness and mental wellbeing. These interventions are of clinical value to enhance adherence rates and avoid comorbidities such as sarcopenia, thus improving disease prognosis.
Latent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein–Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding “nests” of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease.
24 November 2023 in Complementary Therapies in Clinical Practice
Breast, lung and colorectal cancers are 3 of the top 4 most common cancers worldwide. Their treatment with chemotherapy often results in adverse effects on quality of life, fatigue and functional exercise capacity amongst patients. Mind-body therapies, including yoga, Tai chi and Qigong, are commonly used as complementary and alternative therapies in cancer. This meta-analysis evaluates the effects of yoga, Tai chi and Qigong in alleviating the adverse effects of chemotherapy. Various databases were systematically interrogated using specific search terms, returning 1901 manuscripts. Removal of duplicates, irrelevant studies, those lacking available data and applying inclusion/exclusion criteria reduced this number to 9 manuscripts for inclusion in the final meta-analyses. Mean differences were calculated to determine pooled effect sizes using RStudio. This is the first systematic review and meta-analysis to demonstrate significant improvements in fatigue for colorectal cancer patients undergoing chemotherapy with a reduction of -1.40 (95 % CI: -2.24 to -0.56; p = 0.001) observed in mind-body therapy intervention groups. Yoga, Tai chi and Qigong could all be implemented alongside adjuvant therapies to alleviate the adverse effects on colorectal cancer patient fatigue during chemotherapy treatment. This systematic review and meta-analysis is registered on InPlasy: registration number INPLASY202390035; doi: https://doi.org/10.37766/inplasy2023.9.0035.