Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer

Background Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. Methods The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. Results Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. Conclusion CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Efficient radiational outcoupling of electromagnetic energy from hyperbolic metamaterial resonators

Hyperbolic metamaterials were initially proposed in optics to boost radiation efficiencies of quantum emitters. Adopting this concept for antenna design allows approaching long-standing contests in radio physics. For example, broadband impedance matching, accompanied with moderately high antenna gain, is among the existent challenges. Here we propose employing hyperbolic metamaterials for a broadband impedance matching, while a structured layer on top of a metamaterials slab ensures an efficient and directive energy outcoupling to a free space. In particular, a subwavelength loop antenna, placed underneath the matching layer, efficiently excites bulk metamaterial modes, which have well-resolved spatial–temporal separation owing to the hypebolicity of effective permeability tensor. Interplaying chromatic and modal dispersions enable to map different frequencies into non overlapping spatial locations within a compact subwavelength hyperbolic slab. The outcoupling of energy to the free space is obtained by patterning the slab with additional resonant elements, e.g. high index dielectric spheres. As the result, two-order of magnitude improvement in linear gain of the device is predicted. The proposed new architecture can find a use in applications, where multiband or broadband compact devices are required.

Consensus statement on tumour bed localization for radiation after oncoplastic breast surgery

Background: Oncoplastic surgery (OPS) is becoming the new standard of care for breast-conserving surgery. OPS has led to some challenges with adjuvant radiation, particularly when accurate tumour bed (TB) delineation is needed for focused radiation (i.e. accelerated partial breast radiation or boost radiation). Currently, there on no guidelines on tumour bed localization for adjuvant targeted radiation after OPS. Methods: A modified-Delphi method was used to establish consensus amongst a panel of 20 experts in surgical and radiation oncology at the Canadian Locally Advanced Breast Cancer National Consensus (LABCNC) Group and in subsequent online surveys. Results: The main recommendations are as follows: 1) Surgical clips are necessary and should, at a minimum, be placed along the four side walls of the cavity plus one to four clips at the posterior margin if necessary; 2) Operative reports should include pertinent information to help guide the radiation oncologists; 3) Breast surgeons and radiation oncologists should have a basic understanding of OPS techniques and work on “speaking a common language”; and 4) Careful consideration is needed when determining the value of targeted radiation, like boost, in higher level OPS procedures with extensive tissue rearrangement. Conclusion: The panel developed a total of six recommendations on TB delineation for more focused radiation therapy after OPS, with over 80% agreement on each statement. These are summarized along with the corresponding evidence and/or expert opinion.