Protocol for xenografting of BxPC-3 pancreatic tumors using a chorioallantoic membrane model.

The chorioallantoic membrane (CAM) model is an increasingly attractive model for the study of human tumors. However, concise techniques for the use of pancreatic ductal adenocarcinoma BxPC-3 xenografts in CAM assays are not yet available. Here, we present a protocol for the induction of BxPC-3 xenograft tumors with high grafting efficiency. We describe steps for embryo incubation, egg handling, and grafting, each of which has been optimized to prevent fungal contamination and minimize mortality.

Effect of molar mass and alkyl chain length on the surface properties and biocompatibility of poly(alkylene terephthalate)s for potential cardiovascular applications.

Cardiovascular diseases are the leading cause of death worldwide. Treatments for occluded arteries include balloon angioplasty with or without stenting and bypass grafting surgery. Poly(ethylene terephthalate) is frequently used as a vascular graft material, but its high stiffness leads to compliance mismatch with the human blood vessels, resulting in altered hemodynamics, thrombus formation and graft failure. Poly(alkylene terephthalate)s (PATs) with longer alkyl chain lengths hold great potential for improving the compliance. In this work, the effect of the polymer molar mass and the alkyl chain length on the surface roughness and wettability of spin-coated PAT films was investigated, as well as the endothelial cell adhesion and proliferation on these samples. We found that surface roughness generally increases with increasing molar mass and alkyl chain length, while no trend for the wettability could be observed. All investigated PATs are non-cytotoxic and support endothelial cell adhesion and growth. For some PATs, the endothelial cells even reorganized into a tubular-like structure, suggesting angiogenic maturation. In conclusion, this research demonstrates the biocompatibility of PATs and their potential to be applied as materials serving cardiovascular applications.

Hyperthermia Reduces Irradiation-Induced Tumor Repopulation in an In Vivo Pancreatic Carcinoma Model.

Pancreatic cancer has a poor prognosis due to its aggressive nature and ability to metastasize at an early stage. Currently, its management is still a challenge because this neoplasm is resistant to conventional treatment approaches, among which is chemo-radiotherapy (CRT), due to the abundant stromal compartment involved in the mechanism of hypoxia. Hyperthermia, among other effects, counteracts hypoxia by promoting blood perfusion and thereby can enhance the therapeutic effect of radiotherapy (RT). Therefore, the establishment of integrated treatments would be a promising strategy for the management of pancreatic carcinoma. Here, the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models are investigated. This model enables a thorough assessment of the tumor-arresting effect of the combined approach as well as the quantitative evaluation of hypoxia and cell cycle-associated mechanisms by both gene expression analysis and histology. The analysis of the lower CAM allows to investigate the variation of the metastatic behaviors of the cancer cells associated with the treatments. Overall, this study provides a potentially effective combined strategy for the non-invasive management of pancreatic carcinoma.

Hyperthermia Enhances Efficacy of Chemotherapeutic Agents in Pancreatic Cancer Cell Lines.

Chemotherapy (CT) is the standard care for advanced pancreatic ductal adenocarcinoma (PDAC); however, with limited efficacy. Hyperthermia (HT) treatment has been suggested as a sensitizer to improve outcomes. However, the direct effect of the HT and CT combination is not fully understood. Therefore, we aim to assess the direct cytotoxic effect of HT in PDAC cells as monotherapy or in combination with chemotherapeutics. Different temperatures (37-, 40.5-, 41-, and 41.5 °C) and durations (6-, 12-, and 24 h) were tested in PDAC cell lines (BxPC-3, Capan-1, Capan-2, PANC-1, and MIA-PaCa-2). Different concentrations of gemcitabine, 5-fluorouracil, and cisplatin were also tested in these conditions. The impact on cell metabolic activity was determined by an MTS assay. Enhancement of chemosensitivity was assessed by a reduction in half-maximal inhibitory concentration (IC50). HT and chemotherapeutics interactions were classified as antagonistic, additive, or synergistic using the combination index. HT inhibited cell proliferation in a cell type, temperature, and duration-dependent manner. The induction of apoptosis was seen after 6 h of HT treatment, eventually followed by secondary necrosis. The HT and CT combination led to an IC50 reduction of the tested CT. At 12 h of HT, this effect was between 25 to 90% and reached a 95% reduction at 24 h. The additive or synergistic effect was demonstrated in all cell lines and chemotherapeutics, although, again, this depended on cell type, duration, and temperature. HT is cytotoxic and enhances the therapeutic effectiveness of gemcitabine, 5-fluorouracil, and cisplatin on PDAC cells. This result was further confirmed by the decrease in the expression of RRM2, TS, and ERCC1 in BxPC-3 and Capan-2 cells. These observations warrant further study in specific subsets of PDAC patients to improve their clinical outcomes.