RESUMEN
The purpose of our research was to verify the feasibility and effectiveness of a novel three-dimensional printed biopolymer device (3DP-BPD) for duct-to-mucosa pancreaticojejunostomy (PJ) in minipigs. Polylactic acid (PLA) was selected as the raw materials for 3DP-BPD. Three components of a 3DP-BPD were designed and manufactured: hollow stent, supporting disk, and nut. A pancreatic duct dilation model was developed in six minipigs. After 4â¯weeks, minipigs underwent operations with duct-to-mucosa PJ using 3DP-BPD. The operation time and postoperative complications were analyzed. The anastomotic sites were evaluated grossly 4â¯weeks and 24â¯weeks after PJ, and the histological evaluation of anastomotic sites was performed 24â¯weeks after PJ. The operation time of six stitches duct-to-mucosa PJ was 9.1⯱â¯1.7â¯min. All minipigs survived without any adverse events like postoperative pancreatic fistula (POPF). Serum C reactive protein (CRP) and procalcitonin (PCT) levels were normal, and the anastomotic sites were connected tightly on gross observation and touch at 4â¯weeks and 24â¯weeks. Histological examinations indicated that the tissues were continuous between the pancreas and the jejunum. The use of 3DP-BPD did not increase the risk of severe local inflammation and POPF. 3DP-BPD used for duct-to-mucosa PJ is more convenient and clinically feasible for pancreatoenteric reconstruction.
Asunto(s)
Biopolímeros/química , Impresión Tridimensional , Stents , Animales , Proteína C-Reactiva/análisis , Módulo de Elasticidad , Yeyuno/patología , Páncreas/patología , Páncreas/cirugía , Fístula Pancreática/cirugía , Pancreatoyeyunostomía/efectos adversos , Poliésteres/química , Complicaciones Posoperatorias , Porcinos , Porcinos Enanos , Resistencia a la TracciónRESUMEN
Stimulation of Hedgehog (Hh) signaling induces carcinogenesis or promotes cell survival in cancers of multiple organs. In epithelial cancer with aberrant Hedgehog activation, abrogation of Hedgehog signaling by cyclopamine, a naturally occurring Hedgehog-specific small-molecule inhibitor, causes profound inhibition of tumor growth. In the present study, cyclopamine displayed a significant potency in suppressing the proliferation of both estrogen-responsive (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. Cyclopamine induced a robust G1 cell cycle arrest and elicited notable effects on the expression of cyclin D1 through modulation of the MAPK/ERK signaling pathway. Cyclopamine also inhibited the invasive ability of both breast cancer cell lines by suppressing the expression levels of NF-κB, MMP2 and MMP9 protein. Furthermore, in estrogen-responsive MCF-7 cells, cyclopamine significantly downregulated the production of estrogen receptor-α protein. Our results implicate cyclopamine as a novel, potent inhibitor of human breast cancer proliferation and estrogen responsiveness that could potentially be developed into a promising therapeutic agent for the treatment of breast cancer.