Perioperative events influence cancer recurrence risk after surgery.

Surgery is a mainstay treatment for patients with solid tumours. However, despite surgical resection with a curative intent and numerous advances in the effectiveness of (neo)adjuvant therapies, metastatic disease remains common and carries a high risk of mortality. The biological perturbations that accompany the surgical stress response and the pharmacological effects of anaesthetic drugs, paradoxically, might also promote disease recurrence or the progression of metastatic disease. When cancer cells persist after surgery, either locally or at undiagnosed distant sites, neuroendocrine, immune, and metabolic pathways activated in response to surgery and/or anaesthesia might promote their survival and proliferation. A consequence of this effect is that minimal residual disease might then escape equilibrium and progress to metastatic disease. Herein, we discuss the most promising proposals for the refinement of perioperative care that might address these challenges. We outline the rationale and early evidence for the adaptation of anaesthetic techniques and the strategic use of anti-adrenergic, anti-inflammatory, and/or antithrombotic therapies. Many of these strategies are currently under evaluation in large-cohort trials and hold promise as affordable, readily available interventions that will improve the postoperative recurrence-free survival of patients with cancer

Evaluation of Bioactivity and Biocompatibility of Silk Fibroin/TiO2 Nanocomposite

Biodegradable polymer/bioceramic nanocomposites are osteoconductive and can accelerate healing of bone tissue. In this research, silk fibroin (SF)/titanium dioxide (TiO2) nanocomposites were synthesized using different concentrations of TiO2 nanoparticles (0, 5, 10, 15 and 20 wt). The SF/TiO2 nanocomposites were studied in terms of bioactivity and biocompatibility. The in vitro assessment of osteoblasts compatibility indicated that SF inclusion rendered nanocomposite biocompatible whereas presence of TiO2 nanoparticles allowed the cells to adhere and grow on nanocomposite surface and enhanced the bioactivity of the composite. © 2017, Taiwanese Society of Biomedical Engineering

Evaluation of Bioactivity and Biocompatibility of Silk Fibroin/TiO2 Nanocomposite

Biodegradable polymer/bioceramic nanocomposites are osteoconductive and can accelerate healing of bone tissue. In this research, silk fibroin (SF)/titanium dioxide (TiO2) nanocomposites were synthesized using different concentrations of TiO2 nanoparticles (0, 5, 10, 15 and 20 wt). The SF/TiO2 nanocomposites were studied in terms of bioactivity and biocompatibility. The in vitro assessment of osteoblasts compatibility indicated that SF inclusion rendered nanocomposite biocompatible whereas presence of TiO2 nanoparticles allowed the cells to adhere and grow on nanocomposite surface and enhanced the bioactivity of the composite. © 2017, Taiwanese Society of Biomedical Engineering

Stratigraphy of the Gorstian and Ludfordian (upper Silurian) Hemse Group reefs on Gotland, Sweden

The Hemse Group is one of the least understood stratigraphic units of the Silurian sequence of Gotland, Sweden. New results from airborne transient electromagnetic (ATEM) measurements in combination with previously published data from field studies and geophysical investigations shed new light on carbonate platform development during the early- to mid-Ludlow Hemse Group. ATEM reveals a transgressive phase that began near the Wenlock-Ludlow boundary, which resulted in deposition of marls and corresponds roughly to the Hemse limestone units a-c and the Hemse Marl NW. In this phase little or no reef development occurs. The end of the transgressive phase coincides with the weak Linde Event. The following highstand favoured extensive reef growth forming a reef barrier system of both fringing reefs and more rampiform settings with stromatoporoid biostromes and occasional biohermal buildups. The Kuppen-Snabben Unconformity Complex marks an erosional (karstic) sequence boundary and rocky shoreline and the transition from a rampiform setting with reef biostromes towards a more rimmed setting with patch reefs

Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia

Successful treatment of acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) T cells is hampered by toxicity on normal hematopoietic progenitor cells and low CAR T cell persistence. Here, we develop third-generation anti-CD123 CAR T cells with a humanized CSL362-based ScFv and a CD28-OX40-CD3ζ intracellular signaling domain. This CAR demonstrates anti-AML activity without affecting the healthy hematopoietic system, or causing epithelial tissue damage in a xenograft model. CD123 expression on leukemia cells increases upon 5′-Azacitidine (AZA) treatment. AZA treatment of leukemia-bearing mice causes an increase in CTLA-4negative anti-CD123 CAR T cell numbers following infusion. Functionally, the CTLA-4negative anti-CD123 CAR T cells exhibit superior cytotoxicity against AML cells, accompanied by higher TNFα production and enhanced downstream phosphorylation of key T cell activation molecules. Our findings indicate that AZA increases the immunogenicity of AML cells, enhancing recognition and elimination of malignant cells by highly efficient CTLA-4negative anti-CD123 CAR T cells