Duramycin, through binding with phosphatidylethanolamine (PE), has shown potential to be an effective antitumour agent. However, its mode of action in relation to tumour cells is not fully understood. PE expression on the surface of a panel of cancer cell lines was analysed using duramycin and subsequent antibody labelling, and then analysed by flow cytometry. Cell viability was also assessed by flow cytometry using annexin V and propidium iodide. Calcium ion (Ca) release by tumour cells in response to duramycin was determined by spectrofluorometry following incubation with Fluo-3, AM. Confocal microscopy was performed on the cancer cell line AsPC-1 to assess real-time cell response to duramycin treatment. Duramycin could detect cell surface PE expression on all 15 cancer cell lines screened, which was shown to be duramycin concentration dependent. However, higher concentrations induced necrotic cell death. Duramycin induced calcium ion (Ca) release from the cancer cell lines also in a concentration-dependent and time-dependent manner. Confocal microscopy showed an influx of propidium iodide into the cells over time and induced morphological changes. Duramycin induces Ca release from cancer cell lines in a time-dependent and concentration-dependent manner.

Duramycin, through binding with phosphatidylethanolamine (PE),

BackgroundClinical prediction rules (CPRs) developed to predict adverse outcomes of suspected pulmonary embolism (PE) and facilitate outpatient management have limitations in discriminating outcomes for ambulatory cancer patients with unsuspected PE (UPE). The HULL Score CPR uses a 5-point scoring system incorporating performance status (PS) and self-reported new or recently evolving symptoms at UPE diagnosis. It stratifies patients into low, intermediate and high risk for proximate mortality.AimThis study aimed validation of the HULL Score CPR in ambulatory cancer patients with UPE.Patients and methods282 consecutive patients managed under the UPE-acute oncology service in Hull University Teaching Hospitals NHS Trust were included from January 2015 to March 2020. The primary endpoint was all-cause mortality, and outcome measures were proximate mortality for the three risk categories of the Hull Score CPR.Results30-day, 90-day and 180-day mortality for the whole cohort was 3.4% (n=7), 21.1% (n=43) and 39.2% (n= 80), respectively. The HULL Score CPR stratified patients into low 35.5% (100), intermediate 33.7% (95) and high 28.7% (81) risk groups. Correlation of the risk categories with 30-day, 90-day, 180-day mortality and OS was consistent with the derivation cohort (area under the curve [AUC] 0.717 [95% CI 0.522, 0.912], AUC 0.772 [95% CI 0.707, 0.838], AUC 0.751 [95% CI 0.692, 0.809], AUC 0.749 [95% CI 0.686, 0.811], respectively).ConclusionThis study validates the capacity of the HULL Score CPR to stratify proximate mortality risk in ambulatory cancer patients with UPE. The score uses immediately available clinical parameters and is easy to integrate into an acute outpatient oncology setting.