ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)

Go, Ronald S.; Lee, Sandra J.; Shin, Donghoon; Callister, Steven M.; Jobe, Dean A.; Conry, Robert M.; Tarhini, Ahmad A.; Kirkwood, John M.

doi:10.1158/1078-0432.ccr-13-1414

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…AGM-1470, miRNA 646, and interferon alpha downregulate FGF2 expression in cancer cells (Table 5, Figure 4). A phase II clinical study was conducted to evaluate the efficacy of pegintron (peginterferon alpha-2b) in patients with stage IV metastatic melanoma overexpressing FGF2 (Table 6) [87]. The results showed that peginterferon alpha-2b suppressed FGF2 levels in 97% of patients with metastatic melanoma to reference range with a median progression free survival (PFS) and overall survival (OS) of 2.0 and 9.7 months, respectively (Table 6) [87].…”

Section: Targeting the Fgf2/fgfr Pathway In Cancermentioning

confidence: 99%

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

et al. 2016

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Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies.

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Section: Targeting the Fgf2/fgfr Pathway In Cancermentioning

confidence: 99%

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

et al. 2016

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“…A375 cells and U87 cells were shown to express FGF-2 at high levels ( 19 – 21 ). Additionally, FGF-2 strongly stimulates the proliferation and migration of tumor cells ( 5 ).…”

Section: Resultsmentioning

confidence: 99%

Fermentation, Purification, and Tumor Inhibition of a Disulfide-Stabilized Diabody Against Fibroblast Growth Factor-2

et al. 2021

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Angiogenesis is considered one of the hallmarks of cancer and plays a critical role in the development of tumor. Fibroblast growth factor 2 (FGF-2) is a member of the FGF family and participates in excessive cancer cell proliferation and tumor angiogenesis. Thus, targeting FGF-2 was considered to be a promising anti-tumor strategy. A disulfide-stabilized diabody (ds-Diabody) against FGF-2 was produced in Pichia pastoris (GS115) by fermentation and the anti-tumor activity was analyzed. The novel 10-L fed batch fermentation with newly designed media was established, and the maximum production of the ds-Diabody against FGF-2 reached 210.4 mg/L. The ds-Diabody against FGF-2 was purified by Ni2+ affinity chromatography and DEAE anion exchange chromatography. The recombinant ds-Diabody against FGF-2 could effectively inhibit proliferation, migration, and invasion of melanoma and glioma tumor cells stimulated by FGF-2. Furthermore, xenograft tumor model assays showed that the ds-Diabody against FGF-2 had potent antitumor activity in nude mice by inhibiting tumor growth and angiogenesis. The tumor growth inhibition rate of melanoma and glioma was about 70 and 45%, respectively. The tumor angiogenesis inhibition rate of melanoma and glioma was about 64 and 51%, respectively. The results revealed that the recombinant ds-Diabody against FGF-2 may be a promising anti-tumor drug for cancer therapy.

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“…3b). Another clue is that low-dose IFN-α inhibits melanoma cell proliferation by interference with the autocrine growth circuit of FGF-2, a fibroblast growth factor belonging to the same family [29], an effect recently exploited to suppress FGF-2 in patients with metastatic melanoma [30]. Fig.…”

Section: Discussionmentioning

confidence: 99%

Detrimental Impact of Interferon-Based Regimens for Chronic Hepatitis C on Vitamin D/Parathyroid Hormone Homeostasis

Salmi¹,

Barbaglia²,

Smirne³

et al. 2018

TORJ

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Background: Both the anti-infective and anti-inflammatory properties of vitamin D, an essential hormone of calcium homeostasis, have ample support in the literature. The high rates of vitamin D deficiency among patients with chronic hepatitis C are also well known. That supplementation with vitamin D may boost sustained viral response rates in vitamin D deficient, hepatitis C virus (HCV) infected patients undergoing Interferon-alpha (IFN) treatment, on the other hand, is controversial. Surprisingly, studies considering in this latter setting what are the effects of IFN treatment (with or without vitamin D supplementation) on the other major regulator of mineral metabolism, i.e. the Parathyroid hormone (PTH), are lacking. Aim: Evaluate the impact of interferon-based treatment against HCV (±cholecalciferol supplementation) on vitamin D and PTH homeostasis. Methods: A series of 40 consecutive patients received pegylated IFN plus ribavirin to treat chronic hepatitis C. At the discretion of their physician, some of them (N. = 27) received vitamin D supplementation while others did not (N. = 13). All had measured plasma 25-hydroxycholecalciferol and PTH concentrations at baseline, at completion of the 4th (TW4) and 12th treatment week (TW12) and at 24 weeks after the end of therapy (SVR24). Results: Plasma PTH concentration increased significantly from baseline during treatment, raising to 44.8 [30.7-57.2] pg/mL at TW4 (p=0.01), 47.0 [37.1-63.2] pg/mL at TW12 (p=0.006) to return to baseline levels in the follow-up (34.5 [27.6-43.0]; p=0.16). The proportion of patients who satisfied criteria for hyperparathyroidism was higher at TW12 (N=10, 25%) than at TW4 (N=6, 15%). There was no statistical correlation between vitamin D and PTH blood levels (ρ=-0.07; p=0.65). Conclusion: An increase in plasma PTH occurs systematically during IFN treatment of HCV patients and cannot be prevented by vitamin D supplementation.

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ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)

Cited by 9 publications

References 34 publications

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

Fermentation, Purification, and Tumor Inhibition of a Disulfide-Stabilized Diabody Against Fibroblast Growth Factor-2

Detrimental Impact of Interferon-Based Regimens for Chronic Hepatitis C on Vitamin D/Parathyroid Hormone Homeostasis

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