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- W2477338541 abstract "Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and third cause of cancer-related deaths. Because HCC is a relatively chemotherapy-resistant cancer, and many patients are restricted to surgical resection or liver transplantation, there is an urgent need to develop new and improved therapeutic regiments. In the present study, we have investigated the therapeutic effect of a novel oncolytic compound, LTX-401, designed for the local treatment of solid malignancies. In vitro analysis revealed that LTX-401 displayed potent anticancer activity against a broad variety of cancer cell lines. In our model cell line (JM1 HCC), LTX-401 was found to induce necrotic (lytic) cell death followed by the release of potent immune stimulants in the form of Danger-Associated Molecular Pattern molecules (DAMPs) such as HMGB1 and ATP. Ultrastructural analysis by transmission electron microscopy also revealed that a substantial portion of LTX-401-treated JM1 cells contained significantly affected mitochondria. Additionally, cytochrome c was detected in cell supernatants after treatment. The anticancer effect of LTX-401 was investigated in a rat hepatocellular carcinoma model by inoculating JM1 cells into the liver (intrahepatic) of syngeneic Fischer 344 rats. LTX-401 induced a complete regression of HCC tumors by intratumoral injection. Tumor-specific protective immune responses were obtained in previously cured animals, as re-challenge with live and equivalent tumor cells did not lead to tumor growth. Furthermore, intratumoral treatment with LTX-401 was able to eradicate diffuse distant untreated metastasis in the liver. Immuno-histological analysis showed T-cell infiltration into treated tumors. Taken together, intrahepatic treatment with LTX-401 can induce complete regression and long lasting protective tumor-specific immune responses. Citation Format: Brynjar Mauseth, Ji-Hua Shi, Ketil Camilio, Oystein Rekdal, Baldur Sveinbjornsson, Pal-Dag Line. The amphiphatic β(2,2)-amino acid derivative, LTX-401 induces complete regression of experimental hepatocellular carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2347." @default.
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- W2477338541 date "2016-07-15" @default.
- W2477338541 modified "2023-10-18" @default.
- W2477338541 title "Abstract 2347: The amphiphatic β(2,2)-amino acid derivative, LTX-401 induces complete regression of experimental hepatocellular carcinomas" @default.
- W2477338541 doi "https://doi.org/10.1158/1538-7445.am2016-2347" @default.
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