Metformin is a metabolic modulator and radiosensitiser in rectal cancer

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer

Inclusive jet cross sections and dijet correlations in D∗±D^{*\pm} photoproduction at HERA

Inclusive jet cross sections in photoproduction for events containing a $D^*$ meson have been measured with the ZEUS detector at HERA using an integrated luminosity of $78.6 {\rm pb}^{-1}$. The events were required to have a virtuality of the incoming photon, $Q^2$, of less than 1 GeV$^2$, and a photon-proton centre-of-mass energy in the range $130<W_{\gamma p}<280 {\rm GeV}$. The measurements are compared with next-to-leading-order (NLO) QCD calculations. Good agreement is found with the NLO calculations over most of the measured kinematic region. Requiring a second jet in the event allowed a more detailed comparison with QCD calculations. The measured dijet cross sections are also compared to Monte Carlo (MC) models which incorporate leading-order matrix elements followed by parton showers and hadronisation. The NLO QCD predictions are in general agreement with the data although differences have been isolated to regions where contributions from higher orders are expected to be significant. The MC models give a better description than the NLO predictions of the shape of the measured cross sections.Comment: 43 pages, 12 figures, charm jets ZEU

Biodegradation of BTX vapors in a compost medium biofilter

NRC publication: Ye

Characterising the prognostic potential of HLA‑DR during colorectal cancer development

HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent non-neoplastic tissues, for both epithelium (n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p < 0.01) and stroma (p < 0.001). HLA-DR was further reduced in late-stage carcinoma (n = 101) compared to early stage (n = 105), in epithelium (p < 0.001) and stroma (p < 0.01). HLA-DR expression was lower (p < 0.05) in the adjacent non-neoplastic epithelium of patients with cancer recurrence. We demonstrate a progressive loss of HLA-DR in epithelial and stromal tissue compartments during CRC development and show prognostic ability in carcinoma–adjacent non-neoplastic tissues, highlighting the importance of this molecule in the anti-cancer immune response. These findings may have wider implications for immunotherapeutic interventions

Early Years Behaviour Support Program (EYBSP): Application of Tele-Classroom Consulting (TCC) Practices to Support Classroom Teachers to Meet the Challenging and Complex Needs of Students on the Autism Spectrum in the Early Years of Schooling (5-8 Years), Final Report

Students on the autism spectrum have unique learning needs which teachers may find challenging to adequately support. This can be an ongoing concern for teachers in rural and remote communities due to geographical isolation and a lack of professional learning opportunities. To meet the learning needs of students on the spectrum in these regions, teachers often need access to effective, ongoing support delivered in a timely and contextually appropriate manner. This report presents findings from five school community case studies, describing a flexible, multidisciplinary approach that provides classroom teachers with in-situ professional learning to help meet the more complex and individualised needs some students on the spectrum may experience in school settings. The Teleconsultation Classroom (TCC) approach involved a combination of face-to-face visits and more remote support through phone conversations, emails and video conferencing to facilitate collaboration between classroom teachers and outside specialists. This method demonstrates positive results in providing cost-effective, contextualised support to teachers in rural and remote regions, promoting their professional learning and allowing professional relationships to develop despite distance and cost constraints. Guiding principles are outlined to ensure the success, application and sustainability of the TCC approach in rural and remote settings and consideration of its application in more urban settings

Photoswitchable Layer-by-Layer Coatings Based on Photochromic Polynorbornenes Bearing Spiropyran Side Groups

Herein, we present the synthesis of linear photochromic norbornene polymers bearing spiropyran side groups (poly­(SP-R)) and their assembly into layer-by-layer (LbL) films on glass substrates when converted to poly­(MC-R) under UV irradiation. The LbL films were composed of bilayers of poly­(allylamine hydrochloride) (PAH) and poly­(MC-R), forming (PAH/poly­(MC-R))_<i>n</i> coatings. The merocyanine (MC) form presents a significant absorption band in the visible spectral region, which allowed tracking of the LbL deposition process by UV–vis spectroscopy, which showed a linear increase of the characteristic MC absorbance band with increasing number of bilayers. The thickness and morphology of the (PAH/poly­(MC-R))_<i>n</i> films were characterized by ellipsometry and scanning electron microscopy, respectively, with a height of ∼27.5 nm for the first bilayer and an overall height of ∼165 nm for the (PAH/poly­(MC-R))₅ multilayer film. Prolonged white light irradiation (22 h) resulted in a gradual decrease of the MC band by 90.4 ± 2.9% relative to the baseline, indicating the potential application of these films as coatings for photocontrolled delivery systems