@article{GrimmGasserBueteretal.2010,
  author    = {Grimm, Martin and Gasser, Martin and Bueter, Marco and Strehl, Johanna and Wang, Johann and Nichiporuk, Ekaterina and Meyer, Detlef and Germer, Christoph T. and Waaga-Gasser, Ana M. and Thalheimer, Andreas},
  title     = {Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67899},
  year      = {2010},
  abstract  = {Background: The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. Methods: CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Results: Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-b and TNF-a were increased during tumor growth whereas IFN-g showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. Conclusions: This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the situation in human cancer.},
  subject      = {Krebs <Medizin>},
  language  = {en}
}
@article{PelzChuaEsquiveletal.2010,
  author    = {Pelz, Joerg O. W. and Chua, Terence C. and Esquivel, Jesus and Stojadinovic, Alexander and Doerfer, Joerg and Morris, David L. and Maeder, Uwe and Germer, Christoph-Thomas and Kerscher, Alexander G.},
  title     = {Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67875},
  year      = {2010},
  abstract  = {Background: We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes. Methods: One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test. Results: Median survival was 5 months (95\% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95\% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95\% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95\%CI 1.5-5.4); p < 0.001]. Conclusion: A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin.},
  subject      = {Krebs <Medizin>},
  language  = {en}
}