Survival rates for ovarian cancer remain poor, and monitoring and prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha ...(FRα) and the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker.
We evaluated sFRα longitudinally, before and during neo-adjuvant, adjuvant and palliative therapies, and tumour FRα expression status by immunohistrochemistry. The impact of free FRα on the efficacy of anti-FRα treatments was evaluated by an antibody-dependent cellular cytotoxicity assay.
Membrane and/or cytoplasmic FRα staining were observed in 52.7% tumours from 316 ovarian cancer patients with diverse histotypes. Circulating sFRα levels were significantly higher in patients, compared to healthy volunteers, specifically in patients sampled prior to neoadjuvant and palliative treatments. sFRα was associated with FRα cell membrane expression in the tumour. sFRα levels decreased alongside concurrent tumour burden in patients receiving standard therapies. High concentrations of sFRα partly reduced anti-FRα antibody tumour cell killing, an effect overcome by increased antibody doses.
sFRα may present a non-invasive marker for tumour FRα expression, with the potential for monitoring patient response to treatment. Larger, prospective studies should evaluate FRα for assessing disease burden and response to systemic treatments.
Metformin, an anti-hyperglycemic drug, has been known to have antitumor properties for around 15 years. Although there are a number of reports attributing the antitumor function of metformin to its ...impact on energy homeostasis and oxygen re-distribution in tumor microenvironment, detailed mechanisms remain largely unknown. In the past several years, there is an increasing number of publications indicating that metformin can affect various immunological components including lymphocytes, macrophages, cytokines and several key immunological molecules in both human and animal studies. These interesting results appear to be in line with emerging data that suggest associations between immune responses and energy homeostasis/oxygen re-distribution, which may explain effective impacts of metformin on immunotherapies against autoimmune diseases as well as cancers. This review article is to analyse and discuss recent development in the above areas with aim to justify metformin as a new adjuvant for immunotherapy against human cancers. We hope that our summary will help to optimize the application of metformin for various types of human cancers.
Terpenes and terpenoids have been used as enhancers in transdermal formulations for facilitating penetration of drugs into human skin. Knowledge of the correlation between the human skin penetration ...effect (HSPE) and the physicochemical properties of these enhancers is important for facilitating the discovery and development of more enhancers. In this work, the HSPE of 49 terpenes and terpenoids were compared by the
in vitro permeability coefficients of haloperidol (HP) through excised human skin. A first-order multiple linear regression (MLR) model was constructed to link the permeability coefficient of the drug to the lipophilicity, molecular weight, boiling point, the terpene type and the functional group of each enhancer. The Quantitative Structure-Activity Relationship (QSAR) model was derived from our data generated by using standardized experimental protocols, which include: HP in propylene glycol (PG) of 3 mg/ml as the donor solution containing 5% (w/v) of the respective terpene, the same composition and volume of receptor solution, similar human skin samples, in the same set of automated flow-through diffusion cells. The model provided a simple method to predict the enhancing effects of terpenes for drugs with physicochemical properties similar to HP. Our study suggested that an ideal terpene enhancer should possess at least one or combinations of the following properties: hydrophobic, in liquid form at room temperature, with an ester or aldehyde but not acid functional group, and is neither a triterpene nor tetraterpene. Possible mechanisms revealed by the QSAR model were discussed.
Cerebral venous sinus thrombosis is an uncommon cause of stroke with high morbidity and mortality rates from venous infarction, intracranial hemorrhage, and extensive cerebral edema. Endovascular ...treatment with various devices has been proposed as a salvage treatment when standard medical treatment with systemic anticoagulation is ineffective, especially in long segment dural sinus thrombosis. We describe our technique of transvenous endovascular aspiration thrombectomy with large bore thrombectomy catheters, followed by placement of microcatheter for local thrombolytic infusion at the site of thrombosis. We report a retrospective study of angiographic and clinical outcome of six consecutive patients treated with this approach. Endovascular aspiration thrombectomy with large bore catheters followed by continuous local thrombolytic infusion appeared to be a safe and effective salvage treatment for selected patients with cerebral dural venous sinus thrombosis refractory to medical treatment.
Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to ...compare the long-term cardiovascular risks between GnRH agonists and antagonists.
Patients with PCa receiving GnRH agonists or antagonists during 2013–2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups.
In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0–81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7–5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615).
GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.
•GnRH agents may differ in cardiovascular safety.•2479 prostate cancer patients receiving GnRH agonists or antagonist were studied.•GnRH antagonist may be associated with higher long-term cardiovascular risks.•Short-term cardiovascular risks did not differ between GnRH agonists and antagonists.•Those without cardiovascular risk factors had a larger increase in long-term risks.
To understand the attitudes of UK radiology trainees towards artificial intelligence (AI) in Radiology, in particular, assessing the demand for AI education.
A survey, which ran over a period of 2 ...months, was created using the Google Forms platform and distributed via email to all UK training programmes.
The survey was completed by 149 trainee radiologists with at least one response from all UK training programmes. Of the responses, 83.7% were interested in AI use in radiology but 71.4% had no experience of working with AI and 79.9% would like to be involved in AI-based projects. Almost all (98.7%) felt that AI should be taught during their training, yet only one respondent stated that their training programme had implemented AI teaching. Respondents indicated that basic understanding, implementation, and critical appraisal of AI software should be prioritized in teaching. Of the trainees, 74.2% agreed that AI would enhance the job of diagnostic radiologists over the next 20 years. The main concerns raised were information technology/implementation and ethical/regulatory issues.
Despite the current limited availability of AI-based activities and teaching within UK training programmes, UK trainees' attitudes towards AI are mostly positive with many showing interest in being involved with AI-based projects, activities, and teaching.
COVID toe in an adolescent boy: a case report Wong, J S C; Wong, T S; Chua, G T ...
Hong Kong medical journal = Xianggang yi xue za zhi,
04/2022, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Open access
The appearance of chilblain-like lesions was not thought to be associated with a poor disease outcome.2 3 A major limitation of these reports is that only 11% of cases hospitalised tested positive ...for SARS-CoV-2 by polymerase chain reaction (PCR), with the remainder untested or testing negative. Another systematic review also concluded that some, but not all paediatric cases, who developed chilblain-like lesions during the COVID-19 pandemic had positive SARS-CoV-2 PCR, serology or viral particles confirmed in electron microscopy.5 Larger-scale epidemiological study is needed to confirm an association between these chilblain-like lesions and COVID-19 infection. Joshua SC Wong 1 †; TS Wong 1 †; Gilbert T Chua 2 †; Christy Wan 1; SH Lau 1; Samuel CS Ho 1; Jaime S Rosa Duque 2; Ian CK Wong 3,4; Kelvin KW To 5; Winnie WY Tso 2; Christine S Wong 6; Marco HK Ho 2; Janette Kwok 7; CB Chow 1; Paul KH Tam 8,9; Godfrey CF Chan; 2; WH Leung 2; YL Lau 2; Patrick Ip 2; Mike YW Kwan; CUHK 1 1 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong 2 Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 3 Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong 4 Research Department of Practice and Policy, UCL School of Pharmacy, University College London, United Kingdom 5 Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 6 Dermatology Division, Department of Medicine, Queen Mary Hospital, Hong Kong 7 Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong 8 Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong 9 Dr Li Dak-Sum Research Centre, The University of Hong Kong–Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong † Co-first authors
Regulatory B (Breg) cells are endowed with immune suppressive functions. Various human and murine Breg subtypes have been reported. While interleukin (IL)-10 intracellular staining remains the most ...reliable way to identify Breg cells, this technique hinders further essential functional studies. Recent findings suggest that CD9 is an effective surface marker of murine IL-10 competent Breg cells. However, the stability of CD9 and its relevance as a unique marker for human Breg cells, which have been widely characterized as CD24hiCD38hi, have not been investigated. Here, we demonstrate that CD9 expression is sensitive to in vitro B cell stimulations. CD9 expression could either be re-expressed or downregulated in purified CD9-negative B cells and CD9-positive B cells, respectively. We found no significant differences in the Breg differentiation capacity of the CD9-negative and CD9-positive B cells. Furthermore, CD9-positive B cells co-express CD40 and CD86, suggesting their nature as B cell activation or co-stimulatory molecules, rather than regulatory ones. Therefore, we report the relatively unstable CD9 as a distinct surface molecule, indicating the need for further research for a more reliable marker to purify human Breg cells.
With the emergence of multi- and extensive-drug (MDR/XDR) resistant Mycobacterium tuberculosis (M. tb), tuberculosis (TB) persists as one of the world's leading causes of death. Recently, isothermal ...DNA amplification methods received much attention due to their ease of translation onto portable point-of-care (POC) devices for TB diagnosis. In this study, we aimed to devise a simple yet robust detection method for M. tb. Amongst the numerous up-and-coming isothermal techniques, Recombinase Polymerase Amplification (RPA) was chosen for a real-time detection of TB with or without MDR. In our platform, real-time RPA (RT-RPA) was integrated on a lab-on-a-disc (LOAD) with on-board power to maintain temperature for DNA amplification. Sputa collected from healthy volunteers were spiked with respective target M. tb samples for testing. A limit of detection of 102 colony-forming unit per millilitre in 15 min was achieved, making early detection and differentiation of M. tb strains highly feasible in extreme POC settings. Our RT-RPA LOAD platform has also been successfully applied in the differentiation of MDR-TB from H37Ra, an attenuated TB strain. In summary, a quantitative RT-RPA on LOAD assay with a high level of sensitivity was developed as a foundation for further developments in medical bedside and POC diagnostics.
•Automated sample-to-answer detection of drug-resistant Mycobacterium tuberculosis by Recombinase Polymerase Amplification on lab-on-a-disc in 15 min.•Sample can be directly added onto the microfluidic disc for real-time monitoring of RPA by a fluorescent indicator.•Primers designed for PCR were able to differentiate between MDR-TB sample (katG codon 315 point mutation) and H37Ra, an attenuated M. tb strain.•The combined RPA on LOAD platform was able to reach a limit of detection of 102 colony-forming unit per millilitre M. tb culture.•Potential point-of-care extrapolation with RPA reagents pre-loaded on separate chambers of microfluidic disc in a LOAD platform.
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