The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model

James M. Ruda, Kirt S. Beus, Christopher S. Hollenbeak, Ronald Wilson, Brendan C. Stack

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). Design: In vivo murine model, two arm controlled study. Methods: Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 × 106 UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (≥65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Results: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Conclusions: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

Original languageEnglish (US)
Pages (from-to)377-381
Number of pages5
JournalInvestigational New Drugs
Volume24
Issue number5
DOIs
StatePublished - Sep 1 2006

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Fusaric Acid
Nude Mice
Growth
Tumor Burden
Neoplasms
Heterologous Transplantation
Subcutaneous Injections
Survival Analysis
Head and Neck Neoplasms
Oral Administration
Therapeutics
Animal Models

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model",
abstract = "Objective: To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). Design: In vivo murine model, two arm controlled study. Methods: Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 × 106 UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (≥65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Results: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78{\%} of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Conclusions: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.",
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The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model. / Ruda, James M.; Beus, Kirt S.; Hollenbeak, Christopher S.; Wilson, Ronald; Stack, Brendan C.

In: Investigational New Drugs, Vol. 24, No. 5, 01.09.2006, p. 377-381.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model

AU - Ruda, James M.

AU - Beus, Kirt S.

AU - Hollenbeak, Christopher S.

AU - Wilson, Ronald

AU - Stack, Brendan C.

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N2 - Objective: To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). Design: In vivo murine model, two arm controlled study. Methods: Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 × 106 UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (≥65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Results: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Conclusions: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

AB - Objective: To determine whether oral administration of fusaric acid (FA) inhibits tumor growth in an animal model of head and neck cancer (HNSCC). Design: In vivo murine model, two arm controlled study. Methods: Thirty-eight (38) 5-week-old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n = 19) or a sterile saline group (n = 19). A left, lateral flank subcutaneous injection of 2.0 × 106 UM-SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (≥65 mm3), and tumor volumes were recorded after tumor xenografting. Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. Results: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p = 0.00451). By Day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p < 0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p = 0.0142). Conclusions: Single agent oral fusaric acid (1 mg/mL) is an inhibitor of UM-SCC-1 in a murine model. As an orally active agent, it may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.

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