Liver Transplantation for Metastasized Extragastrointestinal Stromal Tumor: A Case Report and an Overview of Literature

Frilling, Andrea; Malagó, Massimo; Testa, G.; Schleyer, Eberhard; Grabellus, Florian; Kronenberger, R; Li, J.; Broelsch, Christoph E.

doi:10.1016/j.transproceed.2010.06.016

Cited by 11 publications

(12 citation statements)

References 28 publications

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“…The 5-year survival rate of diagnosed HCC patients is <10%. 1–2 Therefore, new therapeutic strategies are urgently needed. Sorafenib was initially identified as a Raf (serine/threonine-specific protein kinase) and multikinase inhibitor, which targets Raf, 3 Fms-like tyrosine kinase 3, 4 c-Kit (CD117), 5 p38 (mitogen-activated protein kinase), 6 stem cell growth factor receptor 1, 7 vascular endothelial growth factor receptors, 8 and platelet-derived growth factor receptor-β 9 to induce growth arrest or apoptosis in a variety of malignant tumor cells.…”

mentioning

confidence: 99%

OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma

Zhao

Tian

Puszyk

et al. 2013

Laboratory Investigation

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Sorafenib has been used to treat advanced hepatocellular carcinoma (HCC), but the underlying molecular mechanisms remain controversial and why some patients do not respond to this therapy is poorly understood. In this study, we show that sorafenib triggers cell growth inhibition and apoptosis in HCC cells by directly targeting the mitochondria. Treatment with sorafenib induces rapid mitochondrial fragmentation, which is associated with the deregulation of mitochondria fusion-related protein optic atrophy 1 (OPA1). Exposure of cells or isolated mitochondria to sorafenib substantially induces cytochrome c release. Our data indicate that siRNA-mediated OPA1 knockdown significantly sensitizes HCC cells to sorafenib-induced apoptosis. Furthermore, sorafenib has no apparent apoptotic toxicity to normal human primary hepatocytes. Sorafenib inhibits HCC xenograft tumor growth in vivo and murine xenograft tumor tissue analysis reveals mitochondria fusion protein. OPA1 expression levels are strongly downregulated by sorafenib treatment. Western blotting evaluation of patient HCC with matched non-tumor tissue samples demonstrates that OPA1 expression is decreased in up to 40% of HCC patients. Taken together, we have shown that sorafenib suppresses the tumorigenesis of HCC through the induction of mitochondrial injury via OPA1. Our results provide new insights into the pathogenesis of HCC and suggest that OPA1 is a novel therapeutic target in patients with HCC.

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confidence: 99%

OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma

Zhao

Tian

Puszyk

et al. 2013

Laboratory Investigation

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“…It is reported that the recurrence‐free survival time of patients with gastrointestinal stromal tumors who underwent liver transplantation is 24–69 months. Frilling et al suggested the selection criteria for liver transplantation as: definite diagnosis of gastrointestinal stromal tumor based on immunohistological analysis, patient having a non‐resectable tumor, more than 2 years since the initial surgery, low or medium risk, and KIT or PDGFRA gene mutation‐positive …”

Section: Liver Transplantation For Crlmmentioning

confidence: 99%

“…Frilling et al suggested the selection criteria for liver transplantation as: definite diagnosis of gastrointestinal stromal tumor based on immunohistological analysis, patient having a non-resectable tumor, more than 2 years since the initial surgery, low or medium risk, and KIT or PDGFRA gene mutation-positive. 18 Liver transplantation for 4 patients with liver metastasis of non-resectable pancreatic solid pseudopapillary tumor has been reported so far, and 2 out of these are living donor liver transplantations. The relapse-free survival time was reported at 1 to at least 5 years.…”

Section: Liver Transplantation For Patients With Other Metastatic LIVmentioning

confidence: 99%

Liver transplantation for metastatic liver tumors

Eguchi

Hara

Takatsuki

2017

Hepatology Research

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Liver transplantation for metastatic neuroendocrine tumor in the liver used to be the main reason for liver transplantation for metastatic liver tumor. It is reported that liver transplantation in selected patients with non-resectable metastatic neuroendocrine tumor in the liver had favorable outcomes equivalent to liver transplantation for hepatocellular carcinoma. Recently, liver transplantation for colorectal liver metastasis has attracted attention. According to the SECA study in Oslo, liver transplantation for non-resectable colorectal liver metastasis had a high rate of recurrence but a favorable prognosis. Further discussion on patient selection, attempts at immunosuppressive therapy, and combination with chemotherapy and treatment at the time of relapse are required in order to improve the outcomes of liver transplantation for metastatic liver tumor.

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“…73 However, others described more promising survival with the combination of imatinib, allowing disease-free intervals over 24 mo with the longest survival reaching 10 y at the time of publication. [90][91][92][93] LT for unresectable metastatic GIST may afford prolonged survival in highly selected patients with time to liver metastases > 2 y, low or intermediate risk level of GIST, and positive KIT (CD117) or PDGFR gene mutation status. 93 Similarly, there are only 3 case reports of LT (2 living and 1 deceased donor) for unresectable liver metastases of solid pseudopapillary tumor of the pancreas.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…[90][91][92][93] LT for unresectable metastatic GIST may afford prolonged survival in highly selected patients with time to liver metastases > 2 y, low or intermediate risk level of GIST, and positive KIT (CD117) or PDGFR gene mutation status. 93 Similarly, there are only 3 case reports of LT (2 living and 1 deceased donor) for unresectable liver metastases of solid pseudopapillary tumor of the pancreas. [94][95][96] The patients remain diseasefree at 2 and 5 y after LT. [94][95][96] Selection criteria for LT have yet to be determined.…”

Section: Colorectal Cancermentioning

confidence: 99%

Current status of the organ replacement approach for malignancies and an overture for organ bioengineering and regenerative medicine

et al. 2014

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Liver Transplantation for Metastasized Extragastrointestinal Stromal Tumor: A Case Report and an Overview of Literature

Cited by 11 publications

References 28 publications

OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma

OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma

Liver transplantation for metastatic liver tumors

Current status of the organ replacement approach for malignancies and an overture for organ bioengineering and regenerative medicine

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