Metabolic reprogramming, malignant transformation and metastasis: lessons from chronic lymphocytic leukaemia and prostate cancer.

Metabolic reprogramming is a hallmark of cancer, crucial for malignant transformation and metastasis. Chronic lymphocytic leukaemia (CLL) and prostate cancer exhibit similar metabolic adaptations, particularly in glucose and lipid metabolism. Understanding this metabolic plasticity is crucial for identifying mechanisms contributing to metastasis.

Biomarkers in high grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. HGSC patients typically present with advanced disease, which is often resistant to chemotherapy and recurs despite initial responses to therapy, resulting in the poor prognosis associated with this disease. There is a need to utilise biomarkers to manage the various aspects of HGSC patient care.

Prevalent Atherosclerotic Cardiovascular Disease Among Veterans by Sexual Orientation.

Background: Seven million lesbian, gay, and bisexual (LGB) adults will be aged >50 years by 2030; assessing and addressing their risk for cardiovascular disease is critical.

Methods And Results: We analyzed a nationwide cohort using the Veterans Health Administration data. Sexual orientation (SO) was classified via a validated natural language processing algorithm.

Gestational influenza A virus infection elicits nonresolving vascular dysfunction and T-cell accumulation in the aorta of mice.

T-cell accumulation within the aorta promotes endothelial dysfunction and the genesis of cardiovascular disease, including hypertension and atherosclerosis. Viral infection during pregnancy is also known to mediate marked acute endothelial dysfunction, but it is not clear whether T cells are recruited to the aorta and whether the dysfunction persists postpartum. Here, we demonstrate that influenza A virus (IAV) infection during pregnancy in a murine model resulted in endothelial dysfunction of the aorta, which persisted for up to 60 days postinfection and was associated with higher levels of IFN-γ mRNA expression within the tissue.

Altered expression of vesicular trafficking machinery in prostate cancer affects lysosomal dynamics and provides insight into the underlying biology and disease progression.

Background: This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis.

Methods: Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers.

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies.

A comparative study of circulating tumor cell isolation and enumeration technologies in lung cancer.

Circulating tumor cells (CTCs) have potential as diagnostic, prognostic, and predictive biomarkers in solid tumors. Despite Food and Drug Administration (FDA) approval of CTC devices in various cancers, the rarity and heterogeneity of CTCs in lung cancer make them technically challenging to isolate and analyze, hindering their clinical integration. Establishing a consensus through comparative analysis of different CTC systems is warranted.

Social Determinants of Health and Delivery of Rehabilitation to Older Adults During ICU Hospitalization.

Importance: Older adults with socioeconomic disadvantage develop a greater burden of disability after critical illness than those without socioeconomic disadvantage. The delivery of in-hospital rehabilitation that can mitigate functional decline may be influenced by social determinants of health (SDOH). Whether rehabilitation delivery differs by SDOH during critical illness hospitalization is not known.

Low dose aspirin prevents endothelial dysfunction in the aorta and foetal loss in pregnant mice infected with influenza A virus.

Influenza A virus (IAV) infection in pregnancy resembles a preeclamptic phenotype characterised by vascular dysfunction and foetal growth retardation. Given that low dose aspirin (ASA) is safe in pregnancy and is used to prevent preeclampsia, we investigated whether ASA or NO-conjugated aspirin, NCX4016, resolve vascular inflammation and function to improve offspring outcomes following IAV infection in pregnant mice. Pregnant mice were intranasally infected with a mouse adapted IAV strain (Hkx31; 10 plaque forming units) and received daily treatments with either 200µg/kg ASA or NCX4016 via oral gavage.

High-Intensity Care for Nursing Home Residents with Severe Dementia Hospitalized at the End of Life: A Mixed Methods Study.

Objective: For nursing home residents with severe dementia, high-intensity medical treatment offers little possibility of benefit but has the potential to cause significant distress. Nevertheless, mechanical ventilation and intensive care unit (ICU) transfers have increased in this population. We sought to understand how and why such care is occurring.

Exploring the role of sporadic BRAF and KRAS mutations during colorectal cancer pathogenesis: A spotlight on the contribution of the endosome-lysosome system.

The highly heterogenous nature of colorectal cancer can significantly hinder its early and accurate diagnosis, eventually contributing to high mortality rates. The adenoma-carcinoma sequence and serrated polyp-carcinoma sequence are the two most common sequences in sporadic colorectal cancer. Genetic alterations in adenomatous polyposis coli (APC), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumour protein 53 (TP53) genes are critical in adenoma-carcinoma sequence, whereas v-Raf murine sarcoma viral oncogene homolog B (BRAF) and MutL Homolog1 (MLH1) are driving oncogenes in the serrated polyp-carcinoma sequence.

The impact of continuous calorie restriction and fasting on cognition in adults without eating disorders.

Research into the effects of calorie restriction continues to intrigue those interested in whether it may allow humans to live longer and healthier lives. Animal studies of continuous calorie restriction (CCR) and fasting have demonstrated substantial advantages to health and longevity. However, concerns remain about the impact of restricting calorie intake on human health and cognition.

TLR9 Monotherapy in Immune-Competent Mice Suppresses Orthotopic Prostate Tumor Development.

Prostate cancer is ranked second in the world for cancer-related deaths in men, highlighting the lack of effective therapies for advanced-stage disease. Toll-like receptors (TLRs) and immunity have a direct role in prostate cancer pathogenesis, but TLR9 has been reported to contribute to both the progression and inhibition of prostate tumorigenesis. To further understand this apparent disparity, we have investigated the effect of TLR9 stimulation on prostate cancer progression in an immune-competent, syngeneic orthotopic mouse model of prostate cancer.

Plasminogen activator inhibitor 1 is associated with high-grade serous ovarian cancer metastasis and is reduced in patients who have received neoadjuvant chemotherapy.

High-grade serous ovarian cancer (HGSOC) is the most prevalent and deadliest subtype of epithelial ovarian cancer (EOC), killing over 140,000 people annually. Morbidity and mortality are compounded by a lack of screening methods, and recurrence is common. Plasminogen-activator-inhibitor 1 (PAI-1, the protein product of SERPIN E1) is involved in hemostasis, extracellular matrix (ECM) remodeling, and tumor cell migration and invasion.

P53 and TLR4 expression are prognostic markers informing progression free survival of advanced stage high grade serous ovarian cancer.

Objective: New prognostic biomarkers, and bio-signatures, are urgently needed to facilitate a precision medicine-based approach to more effectively treat patients with high-grade serous ovarian cancer (HGSC). In this study, we analysed the expression patterns of a series of candidate protein biomarkers.

Methods: The panel of markers which included MyD88, TLR4, MAD2, PR, OR, WT1, p53, p16, CD10 and Ki67 was assessed using immunohistochemistry in a tissue microarray (TMA) cohort of n = 80 patients, composed of stage 3-4 HGSCs.

TLR7 promotes chronic airway disease in RSV-infected mice.

Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes.

Insights into Melanoma Clinical Practice: A Perspective for Future Research.

Background: Early diagnosis is the key to improving outcomes for patients with melanoma, and this requires a standardized histological assessment approach. The objective of this survey was to understand the challenges faced by clinicians when assessing melanoma cases, and to provide a perspective for future studies.

Methods: Between April 2022 and February 2023, national and international dermatologists, pathologists, general practitioners, and laboratory managers were invited to participate in a six-question online survey.

Distinct patterns of biomarker expression for atypical intraductal proliferations in prostate cancer.

High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations.

Performance of the HPV E6/E7 mRNA Aptima HPV assay combined with partial genotyping compared with the HPV DNA Cobas 4800 HPV test for use in primary screening: Results from the CERVIVA HPV primary screening study in Ireland.

There are currently several validated HPV tests. However, longitudinal data which spans appropriate age ranges, as well as evaluation of potential screening algorithms are necessary for screening programmes choice of test. The objective of our study was to evaluate the performance of HPV mRNA and HPV DNA testing, including partial genotyping, in routine cervical screening.

Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes.

Altered endosomal-lysosomal biogenesis in melanoma.

Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis.