Effects of rIFN Alpha, Beta, and Gamma on the Morphology, Proliferation, and Cell Surface Antigen Expression of Human Dermal Microvascular Endothelial Cells In Vitro

Ruszczak, Z; Detmar, Michael; Imcke, E.; Orfanos, Constantin E.

doi:10.1111/1523-1747.ep12514496

Cited by 69 publications

(23 citation statements)

References 36 publications

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“…In addition, it has been reported that IFN-ß sensitizes glioma cells to TMZ via induction of p53 and attenuation of O 6 -methylguanine-DNA methyltransferase (MGMT) in vitro (15). Also, several in vitro and in vivo studies (16)(17)(18)(19) have demonstrated an antiangiogenic activity attributed to IFN-ß in tumors. Chronic systemic administration of IFN-· or IFN-ß has been observed to produce regression of vascular tumors including Kaposi sarcoma (20), pulmonary hemangiomatosis (21), and hemangiomas (22); with only a marginal benefit for malignant gliomas (23).…”

Section: Introductionmentioning

confidence: 99%

Potentiation of antiglioma effect with combined temozolomide and interferon-β

Park

Joe²,

Kim³

et al. 2006

Oncol Rep

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Abstract. Temozolomide (TMZ) is a DNA methylating agent that has shown promising antitumor activity against high grade glioma. Interferon-ß (IFN-ß) is known to have antiproliferative and antiangiogenic activities. The aim of this study was to elucidate whether an antiglioma effect could be potentiated by the combination of TMZ and IFN-ß. In vitro, the combination of these drugs suppressed the proliferative and migratory activities, as well as enhance of the apoptosis and cell cycle (S phase) arrest of U-87 cells more efficiently than TMZ or IFN-ß alone. IFN-ß exerted a potent inhibitory effect on the proliferation of human umbilical vein endothelial cells (HUVEC); however, no additive or synergistic effect was observed with the addition of TMZ. To determine in vivo effect, nude mice bearing intracerebral U-87 xenograft inoculation were treated with intraperitoneal administration of PBS, TMZ (15 mg/kg for 3 days), IFN-ß (2x10 5 IU for 15 days), and a TMZ + IFN-ß combination. The combined treatment (median 62.0±8.6 days, P=0.0005) was observed to significantly increase the survival of the animals compared to treatment with PBS (median 30.0±2.5 days), TMZ (median 41.0±3.5 days) or IFN-ß (mean 36.0±2.5 days). These results suggest that antiglioma activity can be enhanced by the combination of TMZ and IFN-ß, providing the possibility for a new strategy development in the management of malignant glioma.

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Section: Introductionmentioning

confidence: 99%

Potentiation of antiglioma effect with combined temozolomide and interferon-β

Park

Joe²,

Kim³

et al. 2006

Oncol Rep

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“…In addition to the well-documented, antiproliferative, and immunomodulatory effects of interferon (IFN), the antiangiogenic properties of IFN have been proven. [7][8][9][10][11] The systemic administration of IFN-␣ decreased the expression of angiogenic factors, such as bFGF, 12 inhibited the angiogenesis, and resulted in regression of human tumors. 13,14 This study evaluates whether IFN-␣-1b can suppress tumor growth, prolong animal life-span, and inhibit recurrence after resection by inhibition of angiogenesis.…”

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confidence: 99%

High-lose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential

et al. 2000

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Postoperative recurrence of human hepatocellular carcinoma (HCC) is the major issue that must be addressed to further improve prognosis. This study was undertaken to investigate the effects of interferon-alfa-1b (IFN-␣-1b) on recurrent tumor and metastasis after curative resection in nude mice bearing an HCC xenograft with high metastatic potential. Tumor tissues from LCI-D20, a metastatic model of HCC in nude mice, were orthotopically implanted in 105 nude mice. Eleven days later, 64 mice underwent curative resection of liver tumors. IFN-␣ at different doses was administered subcutaneously to mice with or without resection. In mice without resection, when comparison was made among control, IFN 7.5 ؋ 10 6 U/kg/day, 1.5 ؋ 10 7 U/kg/day for treated groups, and 3 ؋ 10 7 U/kg/day; tumor volume was 8,475 mm 3 ؎ 2,636 mm 3 , 7,963 mm 3 ؎ 3,214 mm 3 , 769 mm 3 ؎ 287 mm 3 , and 13 mm 3 ؎ 9 mm 3 ; incidence of lung metastasis being 100%, 80%, 40%, and 0%; life span was 45 ؎ 4 days, 53 ؎ 8 days, 81 ؎ 6 days, and 105 ؎ 24 days, respectively. In mice with curative resection, when comparison was made among control, IFN 5 ؋ 10 5 U/kg/day, 1 ؋ 10 6 U/kg/day, 4 ؋ 10 6 U/kg/day, 7.5 ؋ 10 6 U/kg/day, 1.5 ؋ 10 7 U/kg/day, and 3 ؋ 10 7 U/kg/day for treated groups; incidence of recurrent tumor was 100%, 100%, 87.5%, 100%, 87.5%, 62.5%, and 12.5%; lung metastasis being 100%, 75%, 87.5%, 50%, 62.5%, 0%, and 0%, respectively. IFN-␣ inhibited neovascularization induced by LCI-D20 tumor specimens implanted into the micropocket of nude mice corneas. Hepatocellular carcinoma (HCC) is one of the most frequent fatal malignancies occurring in Asia and Africa. 1 In China, it is the second major cause of cancer death in males and the third in females. 2,3 Surgical resection is the most important treatment. Unfortunately, the postoperative recurrence rate remains high. 4,5 HCC is generally not sensitive to chemotherapy. HCC is a typical hypervascular tumor. Intrahepatic and lung metastases suggest its hematogenous dissemination. Recently, angiogenesis was proved to be an important factor influencing HCC metastases and recurrence. 6 Therefore, agents that inhibit angiogenesis maybe provide a new approach to suppress the tumor growth and recurrence of HCC. In addition to the well-documented, antiproliferative, and immunomodulatory effects of interferon (IFN), the antiangiogenic properties of IFN have been proven. [7][8][9][10][11] The systemic administration of IFN-␣ decreased the expression of angiogenic factors, such as bFGF, 12 inhibited the angiogenesis, and resulted in regression of human tumors. 13,14 This study evaluates whether IFN-␣-1b can suppress tumor growth, prolong animal life-span, and inhibit recurrence after resection by inhibition of angiogenesis.

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“…The effects of low doses of TNF and IFN␥ on endothelial-cell functions and characteristics, including inhibition of proliferation and alteration of endothelial-cell shape have been described (Frater-Schroder et al, 1987;Friesel et al, 1987;Ruszczak et al, 1990;Sato et al, 1986;Schweigerer et al, 1987;Stolpen et al, 1986). Our study extends these observations by reporting the effects of high doses of TNF and IFN␥ and provides new insights into the requirements for the induction, maintenance and reversibility of the effects on endothelial-cell proliferation and morphology.…”

Section: Discussionmentioning

confidence: 99%