155 results found
Kawka M, Erridge S, Holvey C, et al., 2021, Clinical outcome data of first cohort of chronic pain patients treated with cannabis-based sublingual oils in the United Kingdom – analysis from the UK Medical Cannabis Registry, Journal of Clinical Pharmacology, ISSN: 1552-4604
Cannabis-based medicinal products (CBMPs) are an emerging therapeutic option in the management of primary chronic pain, utilizing the role of the endocannabinoid system in modulating central and peripheral pain processes. Despite promising pre-clinical data there is a paucity of high-quality evidence to support the use of CBMPs for chronic pain. This study aimed to investigate the health-related quality of life outcomes of patients with chronic pain who were prescribed CBMP oil preparations (Adven®, Curaleaf International)This study is a case-series of patients from the UK Medical Cannabis Registry, who were treated with CBMP oils for an indication of chronic pain. The primary outcomes were the changes in Brief Pain Inventory short-form (BPI), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), Visual Analogue Scale (VAS) Pain, General Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L, at 1, 3, and 6 months.110 patients were included. Significant improvements in SQS, EQ-5D-5L pain and discomfort subscale, and Brief Pain Inventory Interference Subscale (p<0.05) at 1, 3, and 6 months were demonstrated. There were no notable differences between cannabis naïve and previous cannabis users in quality-of-life outcomes. The adverse event incidence was 30.0%, with most (n=58, 92.1%) adverse events being mild or moderate in intensity.Treatment of chronic pain with Adven® CBMP oils was associated with an improvement in pain-specific outcomes, HRQoL and self-reported sleep quality. Relative safety was demonstrated over medium-term prescribed use. Whilst these findings must be treated with caution considering the limitations of study design, they can inform future clinical trials.
IntroductionCannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. There is a growing body of evidence from cell culture and animal studies in support of cannabinoids possessing anticancer properties.MethodA database search of peer reviewed articles published in English as full texts between January 1970 and April 2021 in Google Scholar, MEDLINE, PubMed and Web of Science was undertaken. References of relevant literature were searched to identify additional studies to construct a narrative literature review of oncological effects of cannabinoids in pre-clinical and clinical studies in various cancer types.ResultsPhyto-, endogenous and synthetic cannabinoids demonstrated antitumour effects both in vitro and in vivo. However, these effects are dependent on cancer type, the concentration and preparation of the cannabinoid and the abundance of receptor targets. The mechanism of action of synthetic cannabinoids, (−)-trans-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) has mainly been described via the traditional cannabinoid receptors; CB1 and CB2, but reports have also indicated evidence of activity through GPR55, TRPM8 and other ion channels including TRPA1, TRPV1 and TRPV2.ConclusionCannabinoids have shown to be efficacious both as a single agent and in combination with antineoplastic drugs. These effects have occurred through various receptors and ligands and modulation of signalling pathways involved in hallmarks of cancer pathology. There is a need for further studies to characterise its mode of action at the molecular level and to delineate efficacious dosage and route of administration in addition to synergistic regimes.
Erridge S, Salazar O, Kawka M, et al., 2021, An initial analysis of the UK Medical Cannabis Registry: Outcomes analysis of first 129 patients., Neuropsychopharmacol Rep, Vol: 41, Pages: 362-370
AIM: Cannabis-based medicinal products (CBMPs) are prescribed with increased frequency, despite a paucity of high-quality randomized controlled trials. The aim of this study is to analyze the early outcomes of the first series of patients prescribed CBMPs in the UK with respect to effects on health-related quality of life and clinical safety. METHODS: A prospective case series was performed using the UK Medical Cannabis Registry. Primary outcomes were change in patient-reported outcomes measures (EQ-5D-5L, General Anxiety Disorder-7 (GAD-7) and Single-Item Sleep Quality Scale (SQS)) at 1 and 3 months from baseline. The secondary outcome was the incidence of adverse events. Statistical significance was defined by a P-value <.050. RESULTS: There were 129 patients included in the final analysis with a mean age of 46.23 (±14.51) years. The most common indication was chronic pain of undefined etiology (n = 48; 37.2%). The median initial cannabidiol and (-)-trans-Δ⁹-tetrahydrocannabinol daily dose was 20.0 mg (Range: 0.0-768.0 mg) and 3.9 mg (Range: 0.0-660.0 mg), respectively. Statistically significant improvements in health-related quality of life were demonstrated at 1 and 3 months in GAD-7, SQS, EQ-5D-5L pain and discomfort subscale, EQ-5D-5L anxiety and depression subscale, EQ-VAS and EQ-5D-5L index values(P < .050). There were 31 (24.03%) total reported adverse events. CONCLUSION: This study suggests that CBMP therapy may be associated with an improvement in health-related quality-of-life outcomes as self-reported by patients. CBMPs are also demonstrated to be relatively safe in the short to medium-term. These findings must be treated with caution given the limited scope of this initial analysis, with no placebo or an active comparator, with further research required.
Huang K-W, Tan CP, Reebye V, et al., 2021, MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models., Int J Mol Sci, Vol: 22
The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.
Hashimoto A, Sarker D, Reebye V, et al., 2021, Up-regulation of C/EBP alpha inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients., CANCER RESEARCH, Vol: 81, ISSN: 0008-5472
Yatham SS, Perikleous Y, Ezzat A, et al., 2021, Splenocystojejunostomy for the treatment of a symptomatic splenic pseudocyst, ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND, Vol: 103, Pages: E202-E205, ISSN: 0035-8843
Ashraf H, Sodergren M, Mylonas G, et al., 2021, The Identification of Gaze Behaviour and Physiological Markers Associated With Making An Error During Laparoscopic Cholecystectomy, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323
Sharma C, Singh H, Orihuela-Espina F, et al., 2021, Visual gaze patterns reveal surgeons' ability to identify risk of bile duct injury during laparoscopic cholecystectomy, HPB, Vol: 23, Pages: 715-722, ISSN: 1365-182X
BACKGROUND: Bile duct injury is a serious surgical complication of laparoscopic cholecystectomy. The aim of this study was to identify distinct visual gaze patterns associated with the prompt detection of bile duct injury risk during laparoscopic cholecystectomy. METHODS: Twenty-nine participants viewed a laparoscopic cholecystectomy that led to a serious bile duct injury ('BDI video') and an uneventful procedure ('control video') and reported when an error was perceived that could result in bile duct injury. Outcome parameters include fixation sequences on anatomical structures and eye tracking metrics. Surgeons were stratified into two groups based on performance and compared. RESULTS: The 'early detector' group displayed reduced common bile duct dwell time in the first half of the BDI video, as well as increased cystic duct dwell time and Calot's triangle glances count during Calot's triangle dissection in the control video. Machine learning based classification of fixation sequences demonstrated clear separability between early and late detector groups. CONCLUSION: There are discernible differences in gaze patterns associated with early recognition of impending bile duct injury. The results could be transitioned into real time and used as an intraoperative early warning system and in an educational setting to improve surgical safety and performance.
Pinato D, Cortellini A, Sukumaran A, et al., 2021, PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma, BMC Cancer, Vol: 21, ISSN: 1471-2407
BackgroundAfter liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC.MethodsThe study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC.DiscussionThe results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcom
Anand U, Pacchetti B, Anand P, et al., 2021, Cannabis-based medicines and pain: a review of potential synergistic and entourage effects, Pain Management, Vol: 11, Pages: 395-403, ISSN: 1758-1869
The recent legalization of medicinal cannabis in several jurisdictions has spurred the development of therapeutic formulations for chronic pain. Unlike pure delta-9-tetrahydrocannabinol (THC), full-spectrum products contain naturally occurring cannabinoids and have been reported to show improved efficacy or tolerability, attributed to synergy between cannabinoids and other components in the cannabis plant. Although ‘synergy’ indicates that two or more active compounds may produce an additive or combined effect greater than their individual analgesic effect, potentiation of the biological effect of a compound by related but inactive compounds, in combination, was termed the ‘entourage effect’. Here, we review current evidence for potential synergistic and entourage effects of cannabinoids in pain relief. However, definitive clinical trials and in vitro functional studies are still required.
Glasbey JC, Omar O, Nepogodiev D, et al., 2021, Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 88-96, ISSN: 0007-1323
Schneider C, Sodergren MH, Pencavel T, et al., 2020, Prognostic relevance of the posterior resection margin for predicting disease free survival in ampullary adenocarcinoma, SURGICAL ONCOLOGY-OXFORD, Vol: 35, Pages: 211-217, ISSN: 0960-7404
Evans-Harvey K, Erridge S, Karamchandani U, et al., 2020, Comparison of surgeon gaze behaviour against objective skill assessment in laparoscopic cholecystectomy-a prospective cohort study, International Journal of Surgery, Vol: 82, Pages: 149-155, ISSN: 1743-9159
BackgroundEye tracking technology may provide the basis of a novel, objective technical skill assessment in surgery. Past research has showed differences in the gaze patterns between expert and novice surgeons. The aim of this study was to investigate the relationship between gaze behaviors and technical skill during laparoscopic cholecystectomy as determined by objective assessment scores.MethodsGaze behaviors of surgeons performing laparoscopic cholecystectomies were mapped using wearable eye tracking apparatus. Two impartial surgeons retrospectively analyzed video footage of the procedure to perform Objective Structured Assessment of Technical Skill (OSATS) assessments. Primary endpoints were correlation between gaze behaviours (dwell time (%) and fixation frequency (count/s)) and OSATS scores. Dwell time was defined as the percentage of time spent fixating on particular visual areas of interest (AOI). Pearson's correlation coefficient was used to estimate the relationship between primary endpoints and AOIs. Statistical significance was set at p < 0.05.Results13 procedures were analyzed. Throughout all operative segments, a negative correlation was present between operating theatre dwell time and OSATS scores (p < 0.05). During dissection of Calot's triangle, there was a strong positive correlation between laparoscopic screen dwell time and OSATS scoring [r = 0.655, p < 0.05]. Scrub nurse dwell time during dissection of Calot's triangle showed a strong negative correlation with OSATS scoring [r = −0.619, p < 0.05]. During dissection of gallbladder fossa, operating theatre fixation frequency negatively correlated against OSATS scores [r = −0.566, p < 0.05].ConclusionThe results suggest a greater focus on significant visual stimuli alongside a lack of attention to non-essential stimuli during critical stages of the operative period is associated with greater technical skill. This aids the validation of eye tracking as an adjunct high-stak
Gavriilidis P, Sutcliffe RP, Roberts KJ, et al., 2020, No difference in mortality among ALPPS, two-staged hepatectomy, and portal vein embolization/ligation: A systematic review by updated traditional and network meta-analyses, HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, Vol: 19, Pages: 411-419, ISSN: 1499-3872
Erridge S, Mangal N, Salazar O, et al., 2020, Cannflavins - From plant to patient: A scoping review., Fitoterapia, Vol: 146, Pages: 1-10, ISSN: 0367-326X
INTRODUCTION: Cannflavins are a group of prenylflavonoids derived from Cannabis sativa L.. Cannflavin A (CFL-A), B (CFL-B) and C (CFL-C) have been heralded for their anti-inflammatory properties in pre-clinical evaluations. This scoping review aims to synthesise the evidence base on cannflavins to provide an overview of the current research landscape to inform research strategies to aid clinical translation. METHODS: A scoping review was conducted of EMBASE, MEDLINE, Pubmed, CENTRAL and Google Scholar databases up to 26th February 2020. All studies describing original research on cannflavins and their isomers were included for review. RESULTS: 26 full text articles were included. CFL-A and CFL-B demonstrated potent anti-inflammatory activity via inhibition of 12-o-tetradecanoylphorbol 13-acetate induced PGE2 release (CFL-A half maximal inhibitory concentration (IC50): 0.7 μM; CFL-B IC50: 0.7 μM) and microsomal prostaglandin E synthase-1 (CFL-A IC50: 1.8 μM; CFL-B IC50: 3.7 μM). Outcomes were also described in preclinical models of anti-oxidation (CFL-A), anti-parasitic activity (CFL-A, CFL-C), neuroprotection (CFL-A) and cancer (Isocannflavin B, a CFL-B isomer). In-silico screening identified that CFL-A has binding affinity with viral proteins that warrant further investigation. CONCLUSIONS: Cannflavins demonstrate a number of promising therapeutic properties, most notably as an anti-inflammatory agent. Low yields of extraction however have previously limited research to small pre-clinical investigations. Identification of cannflavin-rich chemovars, novel extraction techniques and recent identification of a biosynthetic pathway will hopefully allow research to be scaled appropriately. In order to fully evaluate the therapeutic properties of cannflavins focused research now needs to be embedded within institutions with a track-record of clinical translation.
Anand U, Jones B, Korchev Y, et al., 2020, CBD effects on TRPV1 signaling pathways in cultured DRG neurons, Journal of Pain Research, Vol: 2020, Pages: 2269-2278, ISSN: 1178-7090
Introduction: Cannabidiol (CBD) is reported to produce pain relief, but the clinically relevant cellular and molecular mechanisms remain uncertain. The TRPV1 receptor integrates noxious stimuli and plays a key role in pain signaling. Hence, we conducted in vitro studies, to elucidate the efficacy and mechanisms of CBD for inhibiting neuronal hypersensitivity in cultured rat sensory neurons, following activation of TRPV1. Methods: Adult rat dorsal root ganglion (DRG) neurons were cultured, and supplemented with the neurotrophic factors NGF and GDNF, in an established model of neuronal hypersensitivity. 48 h after plating, neurons were stimulated with CBD (Adven 150, EMMAC Life Sciences) at 1, 10, 100 nMol/L and 1, 10 and 50 µMol/L. In separate experiments, DRG neurons were also stimulated with capsaicin with or without CBD (1 nMol/L to10 µMol/L), in a functional calcium imaging assay. The effects of the adenylyl cyclase activator forskolin and the calcineurin inhibitor cyclosporin were determined. We also measured forskolin-stimulated cAMP levels, without and after treatment with CBD, using a homogenous time resolved fluorescence (HTRF) assay. The results were analysed using Student’s t-test. Results: DRG neurons treated with 10 and 50 µMol/L CBD showed calcium influx, but not at lower doses. Neurons treated with capsaicin demonstrated robust calcium influx, which was dose-dependently reduced in the presence of low dose CBD (IC50 = 100 nMol/L). The inhibition or desensitization by CBD was reversed in the presence of forskolin and cyclosporin. Forskolin stimulated cAMP levels were significantly reduced in CBD treated neurons.Conclusions: CBD at low doses corresponding to plasma concentrations observed physiologically, inhibits or desensitizes neuronal TRPV1 signalling by inhibiting the adenylyl cyclase – cAMP pathway, which is essential for maintaining TRPV1 phosphorylation and sensitization. CBD also facilitated calcineurin-med
Schneider C, Thompson S, Totz J, et al., 2020, Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 34, Pages: 4702-4711, ISSN: 0930-2794
BackgroundThe laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration.MethodsIntraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes.ResultsThe primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference − 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with l
Sodergren MH, Mangal N, Wasan H, et al., 2020, Immunological combination treatment holds the key to improving survival in pancreatic cancer, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol: 146, Pages: 2897-2911, ISSN: 0171-5216
Sarker D, Plummer R, Meyer T, et al., 2020, MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial, Clinical Cancer Research, Vol: 26, Pages: 3936-3946, ISSN: 1078-0432
PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.
Kassanos P, Berthelot M, Kim JA, et al., 2020, Smart sensing for surgery from tethered devices to wearables and implantables, IEEE Systems Man and Cybernetics Magazine, Vol: 6, Pages: 39-48, ISSN: 2333-942X
Recent developments in wearable electronics have fueled research into new materials, sensors, and microelectronic technologies for the realization of devices that have increased functionality and performance. This is further enhanced by advances in fabr ication methods and printing techniques, stimulating research on implantables and the advancement of existing medical devices. This article provides an overview of new designs, embodiments, fabrication methods, instrumentation, and informatics as well as the challenges in developing and deploying such devices and clinical applications that can benefit from them. The need for and use of these technologies across the perioperative surgical-care pathway are highlighted, along with a vision for the future and how these tools can be adopted by potential end users and health-care systems.
Yatham S, Perikleous Y, Ezzat A, et al., 2020, A Case of Atypical Splenic Subcapsular Pancreatic Pseudocyst, International Surgical Conference of the Association-of-Surgeons-in-Training, Publisher: WILEY, Pages: 92-93, ISSN: 0007-1323
Karamchandani U, Erridge S, Evans-Harvey K, et al., 2020, EYE-TRACKING TECHNOLOGY DIFFERENTIATES VISUAL GAZE PATTERNS BETWEEN TRAINEE ENDOSCOPISTS ACCORDING TO A VALIDATED OBJECTIVE SKILLS ASSESSMENT SCALE, GI Fellows Sessions at Digestive Disease Week / 61st Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract, Publisher: MOSBY-ELSEVIER, Pages: AB113-AB114, ISSN: 0016-5107
Sarker D, Sodergren M, Plummer ER, et al., 2020, Phase Ib dose escalation and cohort expansion study of the novel myeloid differentiating agent MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
da Costa AC, Sodergren M, Jayant K, et al., 2020, Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 26, Pages: 2040-2048, ISSN: 1007-9327
Erridge S, Miller M, Gall T, et al., 2020, A comprehensive patient and public involvement program evaluating perception of cannabis-derived medicinal products in the treatment of acute postoperative pain, nausea, and vomiting using a qualitative thematic framework, Cannabis and Cannabinoid Research, Vol: 5, Pages: 73-80, ISSN: 2578-5125
Introduction: Cannabis-derived medicinal products (CDMPs) have antiemetic properties and in combination with opioids have synergistic analgesic effects in part signaling through the delta and kappa opioid receptors. The objective of this patient and public involvement program was to determine perception of perioperative CDMPs in our local population to inform design of a clinical trial.Methods: A qualitative evaluation was conducted utilizing a focus group, semistructured interviews and a community event. Analysis was conducted through the framework methodology. Verbatim transcriptions were coded categorically into analytical frameworks for thematic analysis. Emergent themes and associated degree of consensus/dissent were determined. The participant cohort was composed of a group of patients and relatives representative of the target population (M:F=1:1, age range 33–85).Results: Most common coding categories in thematic analysis framework included side-effect profile, trial schedule of events, and safety. Consensus was that potential benefits of CDMPs were attractive compared with the known risk profile of opioid use. Decrease in opioid dependence was agreed to be an appropriate clinical end-point for a randomized controlled clinical trial and there was concurrence of positive opinion of a therapeutic schedule of 5 days. Negative CDMP perceptions included addiction, dysphoria, and adverse effects in psychiatric subpopulations. Sublingual or oral administration was the most acceptable route of administration, with some expressing that inhalation delegitimizes therapeutic properties.Conclusions: The perception of postoperative CDMP therapy was overwhelmingly positive in this West London population. The data from this thematic analysis will inform protocol development of clinical trials to determine analgesic and antiemetic efficacy of CDMPs.
Sarker D, Sodergren M, Plummer ER, et al., 2020, First-in-human phase I trial of small activating RNA (saRNA) oligonucleotide MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC), Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Yoon S, Huang K-W, Andrikakou P, et al., 2019, Targeted delivery of C/EBP alpha-saRNA by RNA aptamers shows anti-tumor effects in a mouse model of advanced PDAC, Molecular Therapy : Nucleic Acids, Vol: 18, Pages: 142-154, ISSN: 2162-2531
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies; it preferentially metastasizes to the liver and is the main cause of death from this disease. In previous studies, small activating RNA against CCAAT/enhancer-binding protein-α (C/EBPα-saRNA) demonstrated efficacy of PDAC in a local subcutaneous tumor model. In this study, we focused on the efficacy of C/EBPα-saRNA in advanced stage PDAC. For targeted delivery, we selected a new anti-transferrin receptor aptamer (TR14), which demonstrated a high binding affinity to target proteins. The TR14 aptamer was internalized with clathrin-mediated endocytosis, distributed in early endosome, late endosome, and lysosome subcellularly. To investigate its anti-tumor effects to advanced PDAC, we conjugated C/EBPα-saRNA to TR14. Treatment of pancreatic cancer cells with the conjugates upregulated expression of C/EBPα and its downstream target p21, and inhibited cell proliferation. For in vivo assays, we established an advanced PDAC mouse model by engrafting luciferase reporter-PANC-1 cells directly into the livers of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After treatment of aptamer-C/EBPα conjugates, we observed significant reduction of tumor growth in this advanced PDAC mouse model. Combinational treatment of the conjugates with gemcitabine also demonstrated enhanced anti-tumor effects in advanced PDAC. This suggests that aptamer-C/EBPα conjugates could be used as an adjuvant, along with other conventional anti-cancer drugs in advanced PDAC. In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC.
Sarker D, Plummer R, Basu B, et al., 2019, First-in-human, first-in-class phase I study of MTL-CEBPA, a RNA oligonucleotide targeting the myeloid cell master regulator C/EBP-alpha, in patients with advanced hepatocellular cancer (HCC), 44th Congress of the European-Society-for-Medical-Oncology (ESMO), Publisher: OXFORD UNIV PRESS, Pages: 168-+, ISSN: 0923-7534
Sodergren M, Tan C, Reebye V, et al., 2019, Targeting myeloid-derived suppressor cells and T cells: Combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model, 44th Congress of the European-Society-for-Medical-Oncology (ESMO), Publisher: OXFORD UNIV PRESS, ISSN: 0923-7534
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