: In this retrospective pilot study, we aim to evaluate the accuracy and reliability of the P-POSSUM and ACS-NSQIP surgical risk calculators in predicting postoperative complications in gynaecological-oncological (GO) robotic surgery (RS). : Retrospective data collection undertaken through a dedicated GO database and patient notes at a tertiary referral cancer centre. Following data lock with the actual post-op event/complication, the risk calculators were used to measure predictive scores for each patient.
View Article and Find Full Text PDFThe small-molecule drug, FTY720 (fingolimod), is a synthetic sphingosine 1-phosphate (S1P) analogue currently used to treat relapsing-remitting multiple sclerosis in both adults and children. FTY720 can cross the blood-brain barrier (BBB) and, over time, accumulate in lipid-rich areas of the central nervous system (CNS) by incorporating into phospholipid membranes. FTY720 has been shown to enhance cell membrane fluidity, which can modulate the functions of glial cells and neuronal populations involved in regulating behaviour.
View Article and Find Full Text PDFIn recentexperiments on co-culture between breast tumour spheroids and activated immune cells, it was observed that the introduction of the stress hormone cortisol resulted in a decreased immune cell infiltration into the spheroids. Moreover, the presence of cortisol deregulated the normal levels of the pro- and anti-inflammatory cytokines IFN-and IL-10. We present an individual-based model to explore the interaction dynamics between tumour and immune cells under psychological stress conditions.
View Article and Find Full Text PDFThe canonical NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway involves a priming step to induce pro-IL-1β followed by a secondary signal such as K efflux to activate inflammasome formation. This then leads to the maturation of IL-1β and the formation of gasdermin D (GSDMD) pores that initiate pyroptosis and mediate IL-1β release. In contrast, primary human monocytes also engage an alternative pathway in response to toll-like receptor (TLR) 4 activation, without the need for a secondary signal.
View Article and Find Full Text PDFHigher stress and anxiety levels are often reported globally. While anecdotal evidence has attributed a myriad of health conditions to stress, the mechanisms are often overlooked. Understanding the role of stress hormones on DNA damage/oxidative stress has implications for disease.
View Article and Find Full Text PDFThe response to psychological stress can differ depending on the type and duration of the stressor. Acute stress can facilitate a "fight or flight response" and aid survival, whereas chronic long-term stress with the persistent release of stress hormones such as cortisol has been shown to be detrimental to health. We are now beginning to understand how this stress hormone response impacts important processes such as DNA repair and cell proliferation processes in breast cancer.
View Article and Find Full Text PDFThis study aimed to assess how female breast cancer survivors (BCS) respond physiologically, hematologically, and perceptually to exercise under heat stress compared to females with no history of breast cancer (CON). Twenty-one females (9 BCS and 12 CON [age; 54 ± 7 years, stature; 167 ± 6 cm, body mass; 68.1 ± 7.
View Article and Find Full Text PDFThe hypothesis that the physiologic response to psychologic stress influences the initiation of cancer is highly controversial. The link between initiating stressors, the psychologic stress response, and disease is plausible, considering that the stress response is associated with defined physiologic outcomes and molecular mechanisms. In light of this, we review the clinical relevance of psychologic stress on the risk of cancer, and we propose potential molecular pathways that may link the stress response to early stages of malignant cell transformation.
View Article and Find Full Text PDFInvestigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth.
View Article and Find Full Text PDFPeople that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood.
View Article and Find Full Text PDFSocial isolation (SI) is a major health risk in older people leading to cognitive decline. This study examined how SI and age influence performance in the novel object recognition (NOR) and elevated plus maze (EPM) tasks in C57BL/6 mice aged 3 or 24 months. Mice were group-housed (groups of 2-3) or isolated for 2 weeks prior to experimentation.
View Article and Find Full Text PDFIntroduction: the aim of this study was to assess the validity of a novel wearable sweat rate monitor against an array of sweat analysis techniques which determine sudomotor function when exercising moderately under heat stress. Construct validity was determined utilising a 5-day short-term heat acclimation (STHA) intervention.
Methods: Nineteen healthy individuals (age: 41 ± 23 years, body mass: 74.
Patients diagnosed with cancer often undergo considerable psychological distress, and the induction of the psychological stress response has been linked with a poor response to chemotherapy. The psychological stress response is mediated by fluctuations of the hormones glucocorticoids (GCs) and catecholamines. Binding to their respective receptors, GCs and the catecholamines adrenaline/noradrenaline are responsible for signalling a wide range of processes involved in cell survival, cell cycle and immune function.
View Article and Find Full Text PDFStress hormones have been shown to be important mediators in driving malignant growth and reducing treatment efficacy in breast cancer. Glucocorticoids can induce DNA damage through an inducible nitric oxide synthase (iNOS) mediated pathway to increase levels of nitric oxide (NO). Using an immune competent mouse breast cancer model and 66CL4 breast cancer cells we identified a novel role of NOS inhibition to reduce stress-induced breast cancer metastasis.
View Article and Find Full Text PDFMinimally invasive, reliable and low-cost in vivo biosensors that enable real-time detection and monitoring of clinically relevant molecules and biomarkers can significantly improve patient health care. Microneedle array (MNA)-based electrochemical sensors offer exciting prospects in this respect, as they can sample directly from the skin. However, their acceptability is dependent on developing a highly scalable and cost-effective fabrication strategy.
View Article and Find Full Text PDFIntroduction: The aim of the study was to evaluate the reliability of five different sweat analysis techniques which measure; whole body sweat rate [WBSR], local sweat rate [LSR] (via technical absorbent [TA] method and KuduSmart monitor), sweat conductivity [SC] and sweat gland activation [SGA] in a female population when exercising moderately under heat stress.
Methods: Fourteen females (age; 26 ± 7 years, body mass; 66.5 ± 7.
The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system , we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS).
View Article and Find Full Text PDFBackground: Psychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE). Chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesize that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis.
View Article and Find Full Text PDFTreatment for chronic constipation in older people is challenging and the condition has a major impact on quality of life. A lack of understanding about the causes of this condition has hampered the development of effective treatments. 5-HT is an important pro-kinetic agent in the colon.
View Article and Find Full Text PDFBackground: Esophageal adenocarcinoma (EAC) is associated with a dismal prognosis. The identification of cancer biomarkers can advance the possibility for early detection and better monitoring of tumor progression and/or response to therapy. The authors present results from the development of a serum-based, 4-protein (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9) biomarker panel for EAC.
View Article and Find Full Text PDFPurpose: The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo.
View Article and Find Full Text PDFObjective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples.
View Article and Find Full Text PDFBreast Cancer Res
September 2012
Accumulating evidence indicates that psychological stress can have deleterious influences on cancer development and progression, but the mechanisms responsible remain unclear. One possible mechanism is suggested by emerging evidence that DNA damage is increased by exposure to stress and stress hormones (for example, cortisol, catecholamines). Possible molecular mechanisms for such effects were the subject of a recent paper by Hara and colleagues, which suggests that chronic stress, through β-adrenergic stimulation, can induce two synergistic pathways that result in accumulation of DNA damage.
View Article and Find Full Text PDFEpinephrine and norepinephrine are produced during psychological stress and can directly bind to cells to induce DNA damage. These effects may have more long-lasting consequences such as DNA mutations resulting in an increased potential for cellular transformation and/or tumor progression. This study examined the molecular effects of a chronic (24 h) in vitro exposure to these stress hormones on murine 3T3 cells.
View Article and Find Full Text PDFObjective: The present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.
Methods: A differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types.