Effective angiostatic treatment in a murine metastatic and orthotopic hepatoma model

Raskopf, E.; Dzienisowicz, C.; Hilbert, Tobias; Rabe, Christian; Leifeld, Ludger; Wernert, Nicolas; Sauerbruch, Tilman; Prieto, Jesús; Qian, Cheng; Caselmann, Wolfgang H.; Schmitz, Volker

doi:10.1002/hep.20724

Cited by 31 publications

(31 citation statements)

References 14 publications

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“…This is a striking finding, as increased intratumoral VEGF generation by the tumor itself might have presented a possible mechanism to escape angiostatic effects of an anti-VEGF treatment and, noteworthy, we also did not reveal elevated intratumoral VEGFmRNA levels in another study. 9 Previous data by Bocci et al suggested that determination of VEGF presents a suitable biochemical surrogate marker for antitumor response. However, in our study -applying a similar but still different therapy -no significant correlation between individual VEGF concentrations and tumor sizes could be identified.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] In one of our previous study, we were able to show that VEGF inhibition reduced effectively metastatic and orthotopic hepatocellular carcinomas. 9 The underlying antitumor mechanism of sFlk-1 secretion is that the secreted Flk-1 fragment sequesters circulating VEGF and subsequently forms VEGFR heterodimers without the activation of the receptor-type tyrosine kinase. [6][7][8] Recently, Bocci et al 10 employed a similar approach.…”

Section: Introductionmentioning

confidence: 99%

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Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice

et al. 2006

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“…Finally, HCC is notoriously hypervascular as evidenced by both its diagnostic perfusion pattern on imaging studies and its propensity for vascular invasion. Several reports have shown a significant overexpression of VEGFR mRNA and protein in human HCC samples (69), and in experimental HCC models, VEGFR blockade diminishes tumor growth (70).…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

Wilhelm

Adnane

Newell

et al. 2008

Molecular Cancer Therapeutics

1,257

861

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Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed. [Mol Cancer Ther 2008;7(10):3129 -40]

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“…Whether the VEGFR1 or VEGFR2 plays a more important role in hypoxiainduced HCC angiogenesis is controversial. Most report that VEGFR2 were more important than VEGFR1 [66][67][68][69][70], but some show their reverse results [71,72], while some other believe that both VEGFR1 and VEGFR2 played important roles, and lie in the different signaling cascades by which VEGF augments HCC development and angiogenesis [73]. The higher levels of VEGF expression during the development of HCC have been shown to be associated with an increase in arterialization and sinusoidal capillarization [58].…”

Section: Sprouting Angiogenesis In Hccmentioning

confidence: 99%

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

Chen

Shi

et al. 2010

Hepatol Int

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Hepatocellular carcinoma (HCC) is naturally resistant to radiotherapy and cytotoxic chemotherapy, leaving surgery as the mainstream therapeutic approach. However, the 5-year recurrence rate after curative resection is as high as 61.5%. The background hepatitis B-or C-induced cirrhosis and the presence of micrometastases at the time of surgery have been regarded as two main causes of recurrence. Recently, accumulating evidence suggests that growth factors and cytokines released during the physiological process of post-surgical liver regeneration could induce the activation of dormant micrometastatic lesions. The establishment of neovasculature to support either liver regeneration or HCC growth involves multiple cell types including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and circulating endothelial progenitors. The crosstalks among these cells are driven by multiple molecules and signaling pathways, including vascular endothelial growth factors and their receptors, platelet-derived growth factor, the angiopoietin/Tie family, hepatocyte growth factor/c-Met signaling, and others. Anti-angiogenic agent targeting liver cancer vasculature has been reported to be able to generate limited survival benefit of the patients. In this review, discussions are focused on various angiogenic mechanisms of HCC and liver regeneration, as well as the prevailing anti-angiogenic strategies.

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Effective angiostatic treatment in a murine metastatic and orthotopic hepatoma model

Cited by 31 publications

References 14 publications

Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice

Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

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