Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease.

Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing.

Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition.

Prognostic Significance of Glucocorticoid Receptor Expression in Cancer: A Systematic Review and Meta-Analysis.

In solid malignancies, the glucocorticoid receptor (GR) signalling axis is associated with tumour progression and GR antagonists are in clinical development. Therefore, GR expression may be a useful potential prognostic or predictive biomarker for GR antagonist therapy in cancer. The aim of this review is to investigate if GR expression in tumours is predictive of overall survival or progression free survival.

Obesity and Cancer Metastasis: Molecular and Translational Perspectives.

Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival.

FK506 binding proteins and inflammation related signalling pathways; basic biology, current status and future prospects for pharmacological intervention.

FK506 binding (FKBP) proteins are part of the highly conserved immunophilin family and its members have fundamental roles in the regulation of signalling pathways involved in inflammation, adaptive immune responses, cancer and developmental biology. The original member of this family, FKBP12, is a well-known binding partner for the immunosuppressive drugs tacrolimus (FK506) and sirolimus (rapamycin). FKBP12 and its analog, FKBP12.

Current perspectives on targeting PIM kinases to overcome mechanisms of drug resistance and immune evasion in cancer.

PIM kinases are a class of serine/threonine kinases that play a role in several of the hallmarks of cancer including cell cycle progression, metabolism, inflammation and immune evasion. Their constitutively active nature and unique catalytic structure has led them to be an attractive anticancer target through the use of small molecule inhibitors. This review highlights the enhanced activity of PIM kinases in cancer that can be driven by hypoxia in the tumour microenvironment and the important role that aberrant PIM kinase activity plays in resistance mechanisms to chemotherapy, radiotherapy, anti-angiogenic therapies and targeted therapies.

FKBPL-based peptide, ALM201, targets angiogenesis and cancer stem cells in ovarian cancer.

Background: ALM201 is a therapeutic peptide derived from FKBPL that has previously undergone preclinical and clinical development for oncology indications and has completed a Phase 1a clinical trial in ovarian cancer patients and other advanced solid tumours.

Methods: In vitro, cancer stem cell (CSC) assays in a range of HGSOC cell lines and patient samples, and in vivo tumour initiation, growth delay and limiting dilution assays, were utilised. Mechanisms were determined by using immunohistochemistry, ELISA, qRT-PCR, RNAseq and western blotting.

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus.

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) ( = 116) or squamous cell carcinoma (SCC) ( = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry.

Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines.

The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is often dysregulated in NSCLC, making it an attractive therapeutic target in this setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975 resistant cells were generated by prolonged treatment in culture with Apitolisib (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age-matched parent cells.

Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway.

5-lipoxygenase is an enzyme responsible for the synthesis of a range of bioactive lipids signalling molecules known collectively as eicosanoids. 5-lipoxygenase metabolites such as 5-hydroxyeicosatetraenoic acid (5-HETE) and a number of leukotrienes are mostly derived from arachidonic acid and have been shown to be lipid mediators of inflammation in different pathological states including cancer. Upregulated 5-lipoxygenase expression and metabolite production is found in a number of cancer types and has been shown to be associated with increased tumorigenesis.

Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients.

In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease.

Coagulopathy in two patients with cystic fibrosis treated with ciprofloxacin.

We report two cases of prolonged blood clotting times as demonstrated by a raised international normalised ratio and elevated activated partial thromboplastin time in patients with cystic fibrosis taking ciprofloxacin. The potential mechanisms of a coagulopathy of this picture as an adverse drug reaction with ciprofloxacin are discussed along with the possible clinical consequences for patients with cystic fibrosis.

Bacterial detection of platelets: current problems and possible resolutions.

The greatest transfusion-transmitted disease risk facing a transfusion recipient is that of bacterial sepsis. The prevalence of bacterial contamination in platelets and red blood cells is approximately 1 in 3,000 units transfused. The available data indicate that transfusion-associated sepsis develops after 1 in 25,000 platelet transfusions and 1 in 250,000 red blood cell transfusions.

To examine the effectiveness of a hospital-based nurse-led secondary prevention clinic.

Modification of cardiovascular risk factors can reduce the incidence of myocardial infarction (MI), effectively extend survival, decrease the need for interventional procedures, and improve quality of life in persons with known cardiovascular disease. Pharmacological treatments and important lifestyle changes reduce people's risks substantially (by 1/3 to 2/3) and can slow and perhaps reverse progression of established coronary disease. When used appropriately, these interventions are more cost-effective than many other treatments, currently provided by the National Health Service [Department of Health National Service Frameworks: coronary heart disease.