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Abstract Background Esophageal cancer is one of the 10 most common cancers worldwide and its incidence is dramatically increasing. Despite some improvements, the current surveillance protocol with white light endoscopy and random untargeted biopsies collection (Seattle protocol) fails to diagnose dysplastic and cancerous lesions in up to 50% of patients. Therefore, new endoscopic imaging technologies in combination with tumor-specific molecular probes are needed to improve early detection. Herein, we investigated the use of the fluorescent Poly (ADP-ribose) Polymerase 1 (PARP1)-inhibitor PARPi-FL for early detection of dysplastic lesions in patient-derived organoids and transgenic mouse models, which closely mimic the transformation from non-malignant Barrett’s Esophagus (BE) to invasive esophageal adenocarcinoma (EAC). Methods We determined PARP1 expression via immunohistochemistry (IHC) in human biospecimens and mouse tissues. We also assessed PARPi-FL uptake in patient- and mouse-derived organoids. Following intravenous injection of 75 nmol PARPi-FL/mouse in L2-IL1B (n = 4) and L2-IL1B/IL8Tg mice (n = 12), we conducted fluorescence molecular endoscopy (FME) and/or imaged whole excised stomachs to assess PARPi-FL accumulation in dysplastic lesions. L2-IL1B/IL8Tg mice (n = 3) and wild-type (WT) mice (n = 2) without PARPi-FL injection served as controls. The imaging results were validated by confocal microscopy and IHC of excised tissues. Results IHC on patient and murine tissue revealed similar patterns of increasing PARP1 expression in presence of dysplasia and cancer. In human and murine organoids, PARPi-FL localized to PARP1-expressing epithelial cell nuclei after 10 min of incubation. Injection of PARPi-FL in transgenic mouse models of BE resulted in the successful detection of lesions via FME, with a mean target-to-background ratio > 2 independently from the disease stage. The localization of PARPi-FL in the lesions was confirmed by imaging of the excised stomachs and confocal microscopy. Without PARPi-FL injection, identification of lesions via FME in transgenic mice was not possible. Conclusion PARPi-FL imaging is a promising approach for clinically needed improved detection of dysplastic and malignant EAC lesions in patients with BE. Since PARPi-FL is currently evaluated in a phase 2 clinical trial for oral cancer detection after topical application, clinical translation for early detection of dysplasia and EAC in BE patients via FME screening appears feasible.

Measurement(s) diseases and abnormal findings from chest X-ray scans Technology Type(s) AI is used to detect diseases and abnormal findings Sample Characteristic - Location Vietnam

Limonia acidissima L. (LA) is a fruit-bearing tree from the Rutaceae family that thrives in Tra Vinh province, Vietnam. It has been found that chemical compounds contained in LA leaves have antioxidant, antibacterial, anticancer, anti-inflammatory, and larvicidal properties. This study aimed to evaluate the antioxidant activity of leaf power ethanol-extracted using an ultrasound-assisted extraction technique. The input parameters of the process were optimized by the response surface methodology (RSM) including ethanol content (50 – 70 %), temperature (40 – 60 ºC), and time (30 – 50 min). The model response included total polyphenol content (TPC, Y1), and radical scavenging capacity by DPPH (Y2). The results show that the effect of the input parameters on the response of the extraction process was expressed by the quadratic equation with the high R2 values of Y1 (0.9827), and Y2 (0.9644). The optimal conditions for the extraction process were achieved at X1 = 59.7 %, X2 = 49.4 ºC, and X3 = 39.4 min. At this condition, the experimental value ??of TPC (85.79 ± 0.23 mg GAE/g dry weight, d.w) and DPPH (235.01 ± 0.79 µmol TEAC/g d.w) was not the significant difference compared to the predicted value. Furthermore, bioactive components from the leaf extract were quantified using modern GC-MS chromatography with the content of Stigmasterol (228.36 ± 4.95 ppm), Sitosterol (95.44 ± 3.3 ppm), Alpha-Pinene (60.40 ± 1.29 ppm). Antibacterial activity was tested against Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, and Staphylococcus aureus.