Altered expression of vascular endothelial growth factor, fibroblast growth factor‐2 and endostatin in patients with hepatocellular carcinoma

Uematsu, Setsuko; Higashi, Toshihiro; Nouso, Kazuhiro; Kariyama, Kazuya; Nakamura, Shin; Suzuki, Mayumi; Nakatsukasa, Harushige; Kobayashi, Yohnosuke; Hanafusa, Tadashi; Tsuji, Takao; Shiratori, Yasushi

doi:10.1111/j.1440-1746.2005.03726.x

Cited by 69 publications

(57 citation statements)

References 23 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…FGF2, VEGF, and PDGFB are potent mitogenic and angiogenic factors and stimulate tumor growth (45). Expression of VEGF and FGF2 is altered in patients with HCC and, interestingly, VEGF and FGF2 concentrations are elevated before the emergence of HCC (46). By maintaining high levels of expression of these factors on hepatocytic differentiation, mTOR may accelerate abnormal proliferation and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Mammalian Target of Rapamycin Activation Impairs Hepatocytic Differentiation and Targets Genes Moderating Lipid Homeostasis and Hepatocellular Growth

2007

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Mammalian Target of Rapamycin Activation Impairs Hepatocytic Differentiation and Targets Genes Moderating Lipid Homeostasis and Hepatocellular Growth

2007

View full text Add to dashboard Cite

show abstract

“…In vitro studies have shown that FGF5 overexpression has been associated with a number of tumor cell lines (lung, esophagus, melanoma, colon, and prostate; ref. 23), and in hepatocellular carcinomas (HCC), the upregulation of FGF2, 8, 17, and 18 initiates autocrine growth stimulation, cell survival, and neoangiogenesis (24)(25)(26)(27). Further, HCC has been found to develop in transgenic mice overexpressing the hormonal FGF19 (28), and FGF19 is found on an amplicon on chromosome 11q that also invariably contains the adjacent FGF3, FGF4, and Cyclin D1 (CCND1) genes.…”

Section: Autocrine and Paracrine Signalingmentioning

confidence: 99%

Molecular Pathways: Fibroblast Growth Factor Signaling: A New Therapeutic Opportunity in Cancer

Kilgour²,

Smith³

2012

Clinical Cancer Research

382

363

View full text Add to dashboard Cite

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling axis plays an important role in normal organ, vascular, and skeletal development. Deregulation of FGFR signaling through genetic modification or overexpression of the receptors (or their ligands) has been observed in numerous tumor settings, whereas the FGF/FGFR axis also plays a key role in driving tumor angiogenesis. A growing body of preclinical data shows that inhibition of FGFR signaling can result in antiproliferative and/or proapoptotic effects, both in vitro and in vivo, thus confirming the validity of the FGF/FGFR axis as a potential therapeutic target. In the past, development of therapeutic approaches to target this axis has been hampered by our inability to develop FGFR-selective agents. With the advent of a number of new modalities for selectively inhibiting FGF/FGFR signaling, we are now in a unique position to test and validate clinically the many hypotheses that have been generated preclinically.

show abstract

“…FGF signaling regulates fundamental cellular developmental processes (12), and aberrant FGF signaling is associated with tumorigenesis (8,(11)(12)(13). In addition, FGF-2 has potent effects on vascular endothelial cell proliferation (14), and levels are elevated in tumors and/or serum in patients with a variety of cancers, including HCC (15)(16)(17)(18). Recent clinical data suggest that upregulation of alternate proangiogenic signaling pathways, such as the FGF signaling pathway, may play a role in the development of resistance with anti-VEGF therapies (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Phase II, Open-Label Study of Brivanib as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

Finn

Kang

Mulcahy

et al. 2012

Clinical Cancer Research

165

View full text Add to dashboard Cite

Purpose: Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has recently been shown to have activity as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This phase II open-label study assessed brivanib as second-line therapy in patients with advanced HCC who had failed prior antiangiogenic treatment.Experimental Design: Brivanib was administered orally at a dose of 800 mg once daily. The primary objectives were tumor response rate, time to response, duration of response, progression-free survival, overall survival (OS), disease control rate, time to progression (TTP), and safety and tolerability.Results: Forty-six patients were treated. Best responses to treatment with brivanib (N ¼ 46 patients) using modified World Health Organization criteria were partial responses for two patients (4.3%), stable disease for 19 patients (41.3%), and progressive disease for 19 patients (41.3%). The tumor response rate was 4.3%; the disease control rate was 45.7%. Median OS was 9.79 months. Median TTP as assessed by study investigators following second-line treatment with brivanib was 2.7 months. The most common adverse events were fatigue, decreased appetite, nausea, diarrhea, and hypertension.Conclusion: Brivanib had a manageable safety profile and is one of the first agents to show promising antitumor activity in advanced HCC patients treated with prior sorafenib.

show abstract

Altered expression of vascular endothelial growth factor, fibroblast growth factor‐2 and endostatin in patients with hepatocellular carcinoma

Abstract: The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.

Cited by 69 publications

References 23 publications

Mammalian Target of Rapamycin Activation Impairs Hepatocytic Differentiation and Targets Genes Moderating Lipid Homeostasis and Hepatocellular Growth

Mammalian Target of Rapamycin Activation Impairs Hepatocytic Differentiation and Targets Genes Moderating Lipid Homeostasis and Hepatocellular Growth

Molecular Pathways: Fibroblast Growth Factor Signaling: A New Therapeutic Opportunity in Cancer

Phase II, Open-Label Study of Brivanib as Second-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

Contact Info

Product

Resources

About