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Sustained treatment response of metastatic hepatocellular carcinoma with bevacizumab and sorafenib

World Journal of Gastroenterology 2010年第28期16卷 3592-3596页

作者： Christina Wich Abbas Agaimy Deike Strobel thaddaus till wissniowski Arndt Hartmann Matthias Ocker Department of MedicineⅠ University Hospital ErlangenUlmenweg 1891054 ErlangenGermany Department of Pathology University Hospital ErlangenKrankenhausstr.1291054 ErlangenGermany Institute for Surgical Research Philipps University MarburgBaldingerstrasse35033 MarburgGermany

The overall survival for patients with advanced hepatocellular carcinoma(HCC)is still *** the multi-kinase inhibitor sorafenib has recently been approved for this disease,response rates are still low and patients often face dose-limiting toxicities which lead to a reduction in prognosis and treatment *** here report a patient with metastasized HCC who shows a sustained response for more than 30 mo to sorafenib therapy after failure of a first line therapy with gemcitabine,oxaliplatin and bevacizumab.

关键词： Hepatocellular carcinoma Sorafenib Bevacizumab Angiogenesis

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Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

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World Journal of Gastroenterology 2006年第23期12卷 3716-3721页

作者： Johannes Hansler thaddaus till wissniowski Detlef Schuppan Astrid Witte Thomas Bernatik Eckhart Georg Hahn Deike Strobel Department of Medicine 1 Friedrich Alexander University Erlangen NurembergGermany Experimental Hepatology and Ontology Nikolaus Fiebiger Center Friedrich AlexanderUniversity Erlangen Nuremberg Germany Division of Gastroenterology Beth IsraelDeaconess Medical Center Harvard Medical School Boston MAUnited States

AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.

关键词： CD4 CD8 Cytotoxic Immune response Immunology Immunotherapy Interferon gamma T cells NK Therapeutic vaccination

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