The Leisure & Cultural Services Department will present Nobody but a princess..., a multimedia production featuring Nordic singers, dancers from the Hong Kong Ballet and overseas acrobats from November 8 to 10.

A story of a modern princess who discovers her identity and true love through her fantastic journey of wonders, the performance will be staged in a custom-made giant dome, complete with a state-of-the-art kinetic light display and pyrotechnics.

It will be held at 6pm, 7pm and 8.30pm from November 8 to 10 at the Cultural Centre Piazza.

The show will be conducted in English and include a strobe light effect. Admission is free.

Click here for details.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

(Florida Atlantic University) Despite PPE use, reports show that many health care workers contracted COVID-19. A novel training technique reinforces the importance of using proper procedures to put on and take off PPE when caring for patients during the pandemic. Researchers vividly demonstrate how aerosol-generating procedures can lead to exposure of the contagion with improper PPE use. The most common error made by the health care workers was contaminating the face or forearms during PPE removal.

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources

7 January 2020

Purpose: The aim of this retrospective multicentric study was to develop and evaluate a prognostic FDG PET/CT radiomics signature in early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic radiotherapy (SBRT). Material and Methods: Patients from 3 different centers (n = 27, 29 and 8) were pooled to constitute the training set, whereas the patients from a fourth center (n = 23) were used as the testing set. The primary endpoint was local control (LC). The primary tumour was semi-automatically delineated in the PET images using the Fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. A total of 184 IBSI-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the four institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 (1.7 – 63.4) and 25.5 (7.7 – 57.8) months in training and testing sets respectively. In univariate analysis, none of the clinical variables, 2 PET and 2 CT features were significantly predictive of LC. The best predictive models in the training set were obtained by combining one feature from PET, namely information correlation 2 (IC2) and one from CT (Flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (IC2 and Strength), reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio (HR) (p<0.001). The latter model obtained an accuracy of 0.91 (sensitivity 100%, specificity 81%), with a HR undefined (P = 0.023) in the testing set, however other models relying on CT radiomics features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that two radiomic features derived from FDG PET were independently associated with LC in patients with NSCLC undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision-making.

Purpose: To investigate differences between positron emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (PET/CT) in lesion detection and classification in oncological whole-body examinations and to investigate radiation exposure differences between both modalities. Material and Methods: In this prospective, single-center, observational study 1003 oncological examinations (918 patients, mean age 57.8±14.4y) were included. Patients underwent PET/CT and subsequent PET/MRI (149.8±49.7min after tracer administration). Examinations were reviewed by radiologists and nuclear medicine physicians in consensus. Additional findings, characterization of indetermiante findings in PETCT, missed findings in PET/MRI including their clinical relevance and effective dose of both modalities were investigated. McNemar’s test was used to compare lesion detection between both hybrid imaging modalities (p<0.001 indicating statistical significance). Results: Additional information in PET/MRI was reported in 26.3% (264/1003) of examinations compared to PET/CT (p<0.001). Of these, additional malignant findings were detected in 5.3% (53/1003), leading to a change in TNM-staging in 2.9% (29/1003) due to PET/MRI. Definite lesion classification of indeterminate PET/CT findings was possible in 11.1% (111/1003) with PET/MRI. In 2.9% (29/1003), lesions detected in PET/CT were not visible in PET/MRI. Malignant lesions were missed in 1.2% (12/1003) by PET/MRI leading to a change in TNM-staging in 0.5% (5/1003). The estimated mean effective-dose for whole-body PET/CT amounted to 17.6±8.7mSv in comparison to 3.6±1.4mSv in PET/MRI, resulting in a potential dose reduction of 79.6% (p<0.001). Conclusion: PET/MRI improves lesion detection and potentially reduces additional examinations in tumor staging. Especially younger patients may benefit from the clinically relevant dose reduction of PET/MRI compared to PET/CT.

The impact of prostate specific membrane antigen (PSMA) PET/CT on management of prostate cancer (PCa) patients with biochemical recurrence (BCR) is well-established. However, whether and how PSMA PET/CT affects the management of patients undergoing scans for other clinical indications remains unknown. The goal of this study was to determine the impact of ⁶⁸Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications ("basket trial") excluding the two main classical indications: BCR and presurgical staging. Methods: This was a prospective study of 197 patients that aimed to determine the impact of ⁶⁸Ga-PSMA-11 PET/CT on PCa stage and management. Indications for PSMA PET/CT were: initial staging of non-surgical candidates (30 patients) and re-staging after definitive treatment (n = 168). The re-staging cohort comprised: patients re-staged with known advanced metastatic disease (n = 103), after androgen deprivation therapy only (n = 16), after surgery with serum PSA levels <0.2 ng/ml (n = 13), after radiation therapy (RT) not meeting the Phoenix criteria (n = 22) and after other primary local treatments [i.e. high-intensity focused ultrasound (HIFU), focal laser ablation, cryoablation, hyperthermia or irreversible electroporation] (n = 13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre- and post-PET questionnaires completed by referring physicians, electronic chart review and/or patient telephone encounters. Results: PSMA PET/CT changed disease stage in 135/197 (69%) patients (38% up-stage, 30% down-stage and no changes in stage in 32%). Management was affected in 104/182 (57%) patients. Specifically, PSMA PET/CT impacted management of patients who were re-staged after RT without meeting the Phoenix criteria for BCR, after other definitive local treatments and with advanced metastatic disease in 13/18 (72%), 8/12 (67%) and 59/96 (61%), respectively. Conclusion: PSMA PET/CT has a profound impact on stage and management of PCa patients outside of the two main classical indications (BCR and presurgical staging) across all examined clinical scenarios.

The aim of this work was to quantify the uptake of [¹⁸F]BMS-986192, a PD-L1 adnectin PET tracer, in patients with non-small-cell lung cancer (NSCLC). To this end, plasma input kinetic modeling of dynamic tumor uptake data with online arterial blood sampling was performed. In addition, the accuracy of simplified uptake metrics such as standardized uptake value (SUV) was investigated. Methods: Data from a study with [¹⁸F]BMS-986192 in patients with advanced stage NSCLC eligible for nivolumab treatment were used if a dynamic scan was available and lesions were present in the field of view of the dynamic scan. After injection of [¹⁸F]BMS-986192, a 60-minutes dynamic PET-CT scan was started, followed by a 30-min whole body PET-CT scan. Continuous arterial and discrete arterial and venous blood sampling were performed to determine a plasma input function. Tumor time activity curves were fitted by several plasma input kinetic models. Simplified uptake parameters included tumor to blood ratio as well as several SUV measures. Results: Twenty two tumors in nine patients were analyzed. The arterial plasma input single-tissue reversible compartment model with fitted blood volume fraction seems to be the most preferred model as it best fitted 11 out of 18 tumor time activity curves. The distribution volume V_T ranged from 0.4 to 4.8 mL·cm-3. Similar values were obtained with an image derived input function. From the simplified measures, SUV normalized for body weight (SUV_BW) at 50 and 67 minutes post injection correlated best with V_T, with an R² > 0.9. Conclusion: A single tissue reversible model can be used for the quantification of tumor uptake of the PD-L1 PET tracer [¹⁸F]BMS-986192. SUV_BW at 60 minutes post injection, normalized for body weight, is an accurate simplified parameter for uptake assessment of baseline studies. In order to assess its predictive value for response evaluation during PD-(L)1 immune checkpoint inhibition further validation of SUV against V_T based on an image derived input function is recommended.

Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a ⁶⁸Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours (‘MITIGATE’) (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and Methods: The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of ⁶⁸Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. ⁶⁸Ga-NeoBOMB1 was prepared using a kit procedure with a licensed ⁶⁸Ge/⁶⁸Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: ⁶⁸Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUV_max at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion: This Phase I/IIa study provides safety data for ⁶⁸Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other ⁶⁸Ga-labelled radiopharmaceuticals used in clinical routine.

Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available.

Chelsea DeLeon
May 1, 2020; 61:767-777
Research Articles

Matt Egan is back in the hosting chair to chat with producer Chris about the Samsung Galaxy Note 7 and how we feel about phablets. Techworld.com editor Charlotte Jee comes in to explain what is going on at the GDS (government digital service) and why we should care (13:00). Then online editor at Techworld.com Scott Carey chats Instagram stories, why it is a blatant rip off of Snapchat stories and how the social media giant can get away with being so brazen (22:00).  

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4 February 2020