Fibroblasts from normal and UIP lungs differ in their response to growth factors: Whereas normal fibroblasts show a predominantly proliferative response, UIP fibroblasts show an enhanced synthetic activity. Different fibroblast responses may contribute to progressive pulmonary fibrosis in patients with UIP.

Prevention of TGF-β-induced myofibroblast transformation may account for the inhibitory effect of HGF on matrix production. The strong fibrogenic effect of BALF of inactive sarcoidosis corresponds to the worse clinical course of inactive sarcoidosis compared with active disease and may be related to a lack of protective HGF.

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In Germany pancreatic cancer remains a lethal disease with only 3 - 8% of patients surviving 5 years after diagnosis of the tumor (2005). Reasons for this poor situation are advanced and inoperable tumor stages at time of diagnosis and resistance to conventional therapies. One bottleneck in the development of novel therapies is the restricted availability of preclinical models with a high clinical relevance. The aim of our study was to develop well-defined in vivo xenografts derived from patient pancreatic carcinomas to address translational questions. These xenografts can be used for identification of biomarkers and cancer related pathways as well as for the evaluation of targeted therapies. The genesis of pancreatic neoplasm, the progression of tumor growth as wells as the development of resistance can be elucidated with animal models of patient-derived material. And last but not least preclinical data can be used prospectively for efficient stratification of patients. 57 patient tumors were collected from the clinical cooperation partner and transplanted immediately into immune-deficient mice. 14 out of 57 samples could be established so far as passagable pancreatic cancer xenografts (PDX), 5 were identified as inflammations of the pancreas. Interestingly, we observed 4 out of 57 as post-transplant lymphoproliferative disorders (PLTD); 29 failed to grow in mice. All of the engrafted PDX are poor or moderate differentiated adenocarcinomas. Global gene expression analysis and determination of cancer associated mutations were performed from engrafted tumor models. According to clinical data we found K-ras mutations in 13 and additionally p53 mutations in 9 out of 14 PDX. Chemosensitivity was evaluated by transplanting tumor material into cohorts of immune-deficient mice. Beginning from palpable tumor sizes mice were treated with clinically relevant therapies (Gemcitabine, Abraxane, 5FU, Oxaliplatin, Erlotinib as monotherapy or combinations) as well as PDAC untypical drugs like Irinotecan, Vincristine, Avastin and Sorafenib at optimized schedules and doses. The response to Gemcitabine was moderate within the PDX panel. The most efficient therapeutic was Abraxane. Additionally, we could establish a luciferase expressing PDX for in vivo imaging of orthotopic tumor grafts. Patient-derived xenografts are a crucial tool for the prediction of therapy and potentially relevant for the implication into clinical decisions. We have successfully developed a panel of 14 pancreatic cancer PDX for translational research projects. Citation Format: Diana Behrens, Diana Anders, Cora Hallas, Jessica Pahle, Iduna Fichtner. In vivo models of pancreatic cancer for translational medicine. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A100.

In Germany pancreatic cancer remains a lethal disease with only 3-8% of patients surviving 5 years after diagnosis of the tumor (2005). Reasons for this poor situation are advanced and inoperable tumor stages at time of diagnosis and resistance to conventional therapies. One bottleneck in the development of novel therapies is the restricted availability of preclinical models with a high clinical relevance. The aim of our study was to develop well-defined in vivo xenografts derived from patient pancreatic carcinomas to address translational questions. These xenografts can be used for identification of biomarkers and cancer related pathways as well as for the evaluation of targeted therapies. The genesis of pancreatic neoplasm, the progression of tumor growth as wells as the development of resistance can be elucidated with animal models of patient-derived material. And last but not least, preclinical data can be used prospectively for efficient stratification of patients. Fifty-two patient tumors were collected from the clinical cooperation partner and transplanted immediately into immune-deficient mice. Nine out of 52 samples could be established so far as passagable pancreatic cancer xenografts (PDX), 5 were identified as inflammations of the pancreas. Interestingly, we observed 4 out of 52 as post-transplant lymphoproliferative disorders (PLTD). Twenty-nine failed to grow in mice and 5 are still under observation and potential candidates for the model library. All of the engrafted PDX are poor or moderate differentiated adenocarcinomas. Global gene expression analysis and determination of cancer associated mutations were performed from engrafted tumor models. According to clinical data we found K-ras mutations in 8 and additionally p53 mutations in 4 out of 9 PDX. Chemosensitivity was evaluated by transplanting tumor material into cohorts of immune-deficient mice. Beginning from palpable tumor sizes mice were treated with 5-fluorouracil, Irinotecan, Vincristine, Avastin, Gemcitabine and Sorafenib at optimized schedules and doses. The most efficient therapeutics were Gemcitabine and Irinotecan, whereas the growth of PDX was only marginally inhibited by Vincristine and Avastin. Patient-derived xenografts are a crucial tool for the prediction of therapy and potentially relevant for the implication into clinical decisions. We have successfully developed a panel of 9 pancreatic cancer PDX for translational research projects. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A10. Citation Format: Diana Behrens, Cora Hallas, Diana Anders, Iduna Fichtner. In vivo models of pancreatic cancer for translational medicine. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A10.