Tumor priming by Apo2L/TRAIL reduces interstitial fluid pressure and enhances efficacy of liposomal gemcitabine in a patient derived xenograft tumor model.

Interstitial fluid pressure (IFP) is elevated in tumors and high IFP, a negative cancer prognosticator, is known to limit the uptake and efficacy of anti-tumor therapeutics. Approaches that alter the tumor microenvironment and enhance uptake of therapeutics are collectively referred to as tumor "priming". Here we show that the cytotoxic biological therapy Apo2L/TRAIL can prime the tumor microenvironment and significantly lower IFP in three different human tumor xenograft models (Colo205, MiaPaca-2 and a patient gastrointestinal adenocarcinoma tumor xenograft).

Influence of the implantation site on the sensitivity of patient pancreatic tumor xenografts to Apo2L/TRAIL therapy.

Objectives: We have previously demonstrated activity of Apo2L/TRAIL against patient pancreatic tumor xenografts. Here, we have examined the influence of the tumor implantation site on therapeutic response of orthotopic tumors and their metastases to Apo2L/TRAIL.

Methods: Sensitivity of 6 patient pancreatic tumor xenografts to Apo2L/TRAIL was determined in a subcutaneous model.

Origin of the vasculature supporting growth of primary patient tumor xenografts.

Background: Studies of primary patient tumor xenografts grown in immunodeficient mice have shown that these tumors histologically and genetically closely resemble the original tumors. These patient xenograft models are becoming widely used for therapeutic efficacy studies. Because many therapies are directed at tumor stromal components and because the tumor microenvironment also is known to influence the response of a tumor to therapy, it is important to understand the nature of the stroma and, in particular, the vascular supply of patient xenografts.

Lung cancer xenografting alters microRNA profile but not immunophenotype.

Lung tumor xenografts grown in immunocompromised mice provide a renewable source of tumor tissue for research and a means to study individualized response to chemotherapy. Critical to this utility is verification that the xenograft cells retain core phenotypic characteristics of the original tumor. We compared eight non-small cell lung carcinomas with their corresponding xenografts grown in mice with severe combined immunodeficiency by way of histology, immunohistochemistry, and microRNA expression profiling.

The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice.

BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the fact that this member of the tumor necrosis factor family induces apoptosis in the majority of malignant cells, while normal cells are more resistant. Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the effect is synergistic. The majority of this work has been carried out using cell lines.