Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear.
View Article and Find Full Text PDFLiposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients with secondary acute myeloid leukemia (AML); to date, there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). A total of 189 patients were randomized (median age, 56 years).
View Article and Find Full Text PDFIn this paper the effects of the addition of a paraffin phase change material on the strength and printability of 3D printed concrete are studied. Phase change materials are latent heat storing materials, which garner and release large amounts of energy as they change phase. The addition of phase change materials to concrete produces a composite material with maximised latent and sensible heat storage capacity.
View Article and Find Full Text PDFIt has been established that the acute phase protein, Serum amyloid A (SAA), which is usually synthesized by the liver, is also synthesized by cancer cells and cancer-associated cells in the tumor microenvironment. SAA also activates modulators of autophagy, such as the PI3K/Akt and MAPK signaling pathways. However, the role of SAA in autophagy in breast cancer still remains to be elucidated.
View Article and Find Full Text PDFThe Covid-19 pandemic has spread rapidly across the globe, resulting in more than 3 million deaths worldwide. The symptoms of Covid-19 are usually mild and non-specific, however in some cases patients may develop acute respiratory distress syndrome (ARDS) and systemic inflammation. Individuals with inflammatory or immunocompromising illnesses, such as cancer, are more susceptible to develop ARDS and have higher rates of mortality.
View Article and Find Full Text PDFBackground & Aims: Identifying new approaches to lessen inflammation, as well as the associated malignant consequences, remains crucial to improving the lives and prognosis of patients diagnosed with inflammatory bowel diseases. Although it previously has been suggested as a suitable biomarker for monitoring disease activity in patients diagnosed with Crohn's disease, the role of the acute-phase protein serum amyloid A (SAA) in inflammatory bowel disease remains unclear. In this study, we aimed to assess the role of SAA in colitis-associated cancer.
View Article and Find Full Text PDFChronic inflammation, systemic or local, plays a vital role in tumour progression and metastasis. Dysregulation of key physiological processes such as autophagy elicit unfavourable immune responses to induce chronic inflammation. Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer.
View Article and Find Full Text PDFClin Gastroenterol Hepatol
March 2022
Background & Aims: The IM-UNITI study and long-term extension (LTE) evaluated the long-term efficacy, safety, and immunogenicity of subcutaneous ustekinumab maintenance therapy in patients with Crohn's disease. Here, we report the final results of IM-UNITI LTE through 5 years.
Methods: Patients completing safety and efficacy evaluations at week 44 of the maintenance study were eligible to participate in the LTE and continue the treatment they were receiving.
There is a causal relationship between cancer (including colorectal cancer), chronic systemic inflammation and persistent infections, and the presence of dysregulated circulating inflammatory markers. It is known that aberrant clot formation and coagulopathies occur in systemic inflammation. In colorectal cancer, there is a close link between gut dysbiosis and an inflammatory profile.
View Article and Find Full Text PDFApproximately 10% to 15% of patients with essential thrombocythemia (ET) lack the common driver mutations, so-called "triple-negative" (TN) disease. We undertook a systematic approach to investigate for somatic mutations and delineate gene expression signatures in 46 TN patients and compared the results to those with known driver mutations and healthy volunteers. Deep, error-corrected, next-generation sequencing of peripheral blood mononuclear cells using the HaloPlexHS platform and whole-exome sequencing was performed.
View Article and Find Full Text PDFCytokine Growth Factor Rev
June 2021
Gut dysbiosis contributes to the development of a dysfunctional gut barrier, facilitating the translocation of bacteria and inflammagens, and is implicated in colorectal cancer (CRC) pathogenesis. Such 'leaky gut' conditions result in systemic inflammation, of which a hallmark is increased hypercoagulability. Fluorescence antibody confocal microscopy was used to determine circulating levels of lipopolysaccharide (LPS) in control and CRC populations.
View Article and Find Full Text PDFBackground And Aims: Following induction/maintenance treatment in the UNITI/IM-UNITI studies of ustekinumab for Crohn's disease, patients entered a long-term extension for up to 5 years from induction. Efficacy through 152 and safety through 156 weeks are reported.
Methods: At IM-UNITI Week 44, 567 ustekinumab-treated patients entered the long-term extension and continued to receive blinded subcutaneous ustekinumab on their assigned dose interval, without any subsequent dose adjustment.
Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer's disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation.
View Article and Find Full Text PDFMany chronic diseases, including those classified as cardiovascular, neurodegenerative, or autoimmune, are characterized by persistent inflammation. The origin of this inflammation is mostly unclear, but it is typically mediated by inflammatory biomarkers, such as cytokines, and affected by both environmental and genetic factors. Recently circulating bacterial inflammagens such as lipopolysaccharide (LPS) have been implicated.
View Article and Find Full Text PDFNutritional support continues to receive much attention as a possible intervention to prevent loss of lean tissue mass, promote recovery and re-establish proper immune function in critical care patients. Yet there remains much controversy regarding the clinical efficacy of such interventions. In addition to the direct effect of nutrition in terms of micro- and macronutrient content, nutritional formulations may exert an effect via the physiological response to feeding.
View Article and Find Full Text PDFAliment Pharmacol Ther
July 2018
Background: In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported.
Methods: UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients.
Background: Techniques commonly used to expedite blood transfusions include pneumatically pressurizing red blood cell (RBC) bags or manual syringing its contents. We compared these techniques on RBC hemolysis using a simulated transfusion model.
Study Design And Methods: Fifteen warmed RBC units that were 12.
Background: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.
Methods: We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials.
Objectives: In Crohn's disease (CD), clinical symptoms correspond poorly to inflammatory disease activity. Biomarkers reflective of mucosal and bowel wall inflammation would be useful to monitor disease activity. The EMBARK study evaluated disease activity in patients with ulcerative colitis (UC) and CD, and used endoscopy with or without cross-sectional imaging for biomarker discovery.
View Article and Find Full Text PDFBackground: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening.
View Article and Find Full Text PDFBackground: The prevalence of peanut allergies is increasing. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCTs), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared with long-chain triglycerides (LCTs), which stimulate mesenteric lymph flow and are absorbed in chylomicrons through mesenteric lymph.
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