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.

669 Background: Premalignant pancreatic cellular genotype may remain stable for many years, but compounding conditions can produce rapid malignant cellular transformation. This onset is rarely spontaneous and is often associated with the presence of inflammation. One inflammatory modulator is “tissue factor (TF),” which usually acts in complex with “coagulation factor VIIa (fVIIa)” to initiate coagulation. The role of TF in malignancy and its impact beyond thrombosis on cell proliferation, angiogenesis, and metastasis is well established. This suggests that TF may be a diagnostic marker in the inflammatory microenvironment of the precursor lesions of pancreatic cancer. Aim: To examine the potential of TF concentrations and the fVII:TF ratio within pancreatic cyst fluid as indicators of malignant cellular transformation from benign to malignant. Methods: Cyst fluid was prospectively collected from 31 patients with pancreatic cystic lesions (REC 18/LO/0736) and analysed in a blinded fashion. The level of TF and fVIIa proteins were measured by ELISA, and the fVIIa:TF ratios calculated. A cut-off value for TF concentration was determined using a ROC curve and compared to the conventional assessment parameters, including radiological features, carcinoembryonic antigen (CEA) and amylase. Results: Patients were categorised into four groups based on histology. Significant histological stage-dependent increases in TF level were observed, which corresponded to the progression of the normal ductal epithelium to invasive adenocarcinoma. The mean TF concentration was significantly higher ( p= 0.006) in the high-risk group (high-grade dysplasia & malignant; 1.17 ng/ml, 95% CI 0.68, 1.67) vs the low-risk group (benign & low-grade dysplasia; 0.27 ng/ml, 95% CI 0.1, 0.44). A strong positive correlation between TF concentration and the high-risk group was observed (correlation coefficient 0.746, p < 0.001, the cut-off value for TF 0.75 ng/ml, AUC 0.877, p= 0.002). In addition, the fVIIa:TF ratio, was marginally lower ( p= 0.274) in the high-risk group (mean = 84.82 [95% CI 0, 185.04]) vs the low-risk group (mean = 437.46 [95% CI 0, 901.02]). TF concentrations performed consistently better as an indicator of malignant transformation when compared to the conventional parameters and will be presented at the meeting. Conclusions: Cyst-associated TF levels appear to correlate with the cytological progression to the malignant phenotype, while the fVIIa:TF ratio indicates a breakdown in the ability of the body to contain the disease. Such indicators may allow better presurgical discrimination of malignant potential of tumours and offer a more nuanced tool for monitoring indeterminate cystic lesions. Further work is needed with a larger cohort to confirm these findings.