METHODS: Patients with solid pancreatic lesions ≤ 15 mm in size and a definite diagnosis were included. Lesion stiffness relative to the surrounding pancreatic parenchyma, as qualitatively assessed and documented at the time of EUS elastography, was retrospectively compared with the final diagnosis obtained by fine-needle aspiration/biopsy or surgical resection.
RESULTS: 218 patients were analyzed. The average size of the lesions was 11 ± 3 mm; 23 % were ductal adenocarcinoma, 52 % neuroendocrine tumors, 8 % metastases, and 17 % other entities; 66 % of the lesions were benign. On elastography, 50 % of lesions were stiffer than the surrounding pancreatic parenchyma (stiff lesions) and 50 % were less stiff or of similar stiffness (soft lesions). High stiffness of the lesion had a sensitivity of 84 % (95 % confidence interval 73 % - 91 %), specificity of 67 % (58 % - 74 %), positive predictive value (PPV) of 56 % (50 % - 62 %), and negative predictive value (NPV) of 89 % (83 % - 93 %) for the diagnosis of malignancy. For the diagnosis of pancreatic ductal adenocarcinoma, the sensitivity, specificity, PPV, and NPV were 96 % (87 % - 100 %), 64 % (56 % - 71 %), 45 % (40 % - 50 %), and 98 % (93 % - 100 %), respectively.
CONCLUSIONS: In patients with small solid pancreatic lesions, EUS elastography can rule out malignancy with a high level of certainty if the lesion appears soft. A stiff lesion can be either benign or malignant.
CONCLUSIONS: Herein, the expression profiles, oncogenic roles, regulators and inhibitors of DNMT1 in PDACs are presented and discussed. DNMT1 is overexpressed in PDAC cases compared with non-cancerous pancreatic ducts, and its expression gradually increases from pre-neoplastic lesions to PDACs. DNMT1 plays oncogenic roles in suppressing PDAC cell differentiation and in promoting their proliferation, migration and invasion, as well as in induction of the self-renewal capacity of PDAC cancer stem cells. These effects are achieved via promoter hypermethylation of tumor suppressor genes, including cyclin-dependent kinase inhibitors (e.g., p14, p15, p16, p21 and p27), suppressors of epithelial-mesenchymal transition (e.g., E-cadherin) and tumor suppressor miRNAs (e.g., miR-148a, miR-152 and miR-17-92 cluster). Pre-clinical investigations have shown the potency of novel non-nucleoside DNMT1 inhibitors against PDAC cells. Finally, phase I/II clinical trials of DNMT1 inhibitors (azacitidine, decitabine and guadecitabine) in PDAC patients are currently underway, where these inhibitors have the potential to sensitize PDACs to chemotherapy and immune checkpoint blockade therapy.
METHODS: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast).
RESULTS: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells.
CONCLUSION: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies.