Oncological thermal ablation involves the use of hyperthermic temperatures to damage and treat solid cancers. Thermal ablation is being investigated as a method of treatment in colorectal cancers and has the potential to complement conventional anti-cancer treatments in managing local recurrence and metastatic disease. Photothermal therapy utilises photosensitive agents to generate local heat and induce thermal ablation. There is growing interest in developing nanotechnology platforms to deliver such photosensitive agents. An advantage of nanomedicines is their multifunctionality with the capability to deliver combinations of chemotherapeutics and cancer-imaging agents. To date, there have been no clinical studies evaluating photothermal therapy-based nanomedicines in colorectal cancers. This review presents the current scope of pre-clinical studies, investigating nanomedicines that have been developed for delivering multimodal photothermal therapy to colorectal cancers, with an emphasis on potential clinical applications.

Both mesh options appear to result in similar long- and short-term postoperative outcomes. Further long-term analysis may guide surgeon selection of mesh weight for laparoscopic inguinal hernia repair.

has the potential to increase colorectal cancer detection rate yet be clinically and cost effective.

Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition.

Three-dimensional (3D) spheroidal cell cultures are now recognised as better models of cancers as compared to traditional cell cultures. However, established 3D cell culturing protocols and techniques are time-consuming, manually laborious and often expensive due to the excessive consumption of reagents. Microfluidics allows for traditional laboratory-based biological experiments to be scaled down into miniature custom fabricated devices, where cost-effective experiments can be performed through the manipulation and flow of small volumes of fluid. In this study, we characterise a 3D cell culturing microfluidic device fabricated from a 3D printed master. HT29 cells were seeded into the device and 3D spheroids were generated and cultured through the perfusion of cell media. Spheroids were treated with 5-Fluorouracil for five days through continuous perfusion and cell viability was analysed on-chip at different time points using fluorescence microscopy and Lactate dehydrogenase (LDH) assay on the supernatant. Increasing cell death was observed in the HT29 spheroids over the five-day period. The 3D cell culturing microfluidic device described in this study, permits on-chip anti-cancer treatment and viability analysis, and forms the basis of an effective platform for the high-throughput screening of anti-cancer drugs in 3D tumour spheroids.

This is a repository copy of The role of ABCG2 in modulating responses to anti-cancer photodynamic therapy.

Background5-aminolevulinic acid (5-ALA) is used for fluorescence diagnosis (FD) in neurological, gynaecological and urological malignancies. The Medical Research Council/Efficacy and Mechanism Evaluation (EME) programme/National Institute for Health Research’s Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten) study investigated its use to predict lymph node (LN)-positive disease in colon cancer as an aid to stratified surgery.ObjectivesThe primary objective was to optimise the dose of oral 5-ALA for intraoperative FD of metastatic LNs in colon cancer. Secondary objectives included standardisation of pre-operative computerised tomography (CT) LN reporting, intraoperative fluorescence detection, surgical resection with D3 lymphadenectomy and histopathological examination of resected specimens.DesignThis was a feasibility study to determine optimal strategies for 5-ALA positive LN detection. Patients with locally advanced disease identified using the Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer (FOxTROT) criteria were recruited from two sites between October 2013 and June 2015. Cohort 1 received 20 mg/kg and cohort 2 received 30 mg/kg of oral 5-ALA, 1–6 hours preoperatively. Laparoscopic assessment of fluorescence was performed using the Storz D-Light system (KARL STORZ GmbH & Co. KG; Tuttlingen, Germany), with marking of fluorescent LNs, followed by oncological resection. The specimen was subjected to histological analysis with step sectioning of marked fluorescent LNs. Progression to an evaluation phase using the optimal dosing schedule was dependent on positively identifying at least 2 out of 10 patients with metastatic LN disease in either cohort.ResultsA total of 44 patients were recruited with a male to female ratio of 26 : 18 and a mean age of 71 years (range 52–88 years). Cohort 1 consisted of 18 patients, of whom six had fluorescent primary cancers and three of these had fluorescent LNs. One out of 10 patients with metastatic LN disease had a fluorescent involved LN. Cohort 2 consisted of 26 patients, of whom eight had fluorescent primary cancers and four of these had fluorescent LNs. None of the fluorescent LNs contained disease in this cohort. No serious adverse events (SAEs) occurred but two mild, self-limiting, photosensitivity reactions were observed in cohort 2. The sensitivity and specificity for 5-ALA detection of LN-positive disease were: cohort 1 11.1%, 75%; and cohort 2 0%, 75%.LimitationsThis was a feasibility study exploring the use of 5-ALA for LN disease in a select cohort of patients with advanced colorectal cancer. The study population was small and generalisation to other cancers is not possible. The study was limited by the ability to determine LN-positive patients on the basis of pre-operative CT staging, which is often inaccurate, resulting in our cohorts containing several patients without LN disease.Conclusions5-ALA fluorescent diagnosis has poor sensitivity for discriminating LN-positive colon cancer. Its use as an aid to stratified colon cancer surgery is not supported. No SAEs were observed, suggesting that photosensitisers may be useful for intraoperative FD.Future work5-ALA has poor sensitivity for detecting LN metastases and cannot be recommended for intraoperative staging. Other, more sensitive fluorescent probes are required if this strategy is to be used.Study registrationCurrent Controlled Trials ISRCTN79949827 and EudraCT number 2012–002623–15.Funding detailsThis project was funded by the EME programme, a Medical Research Council and National Institute for Health Research partnership.

This is a repository copy of Understanding the mechanisms of cell death in photothermal nanomedicines.