Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside

Gordon McLennan, Stacy L. Bennett, Shenghong Ju, Andriy Babsky, Navin Bansal, Michelle L. Shorten, Seth Levitin, Laurent Bonnac, Krystoff W. Panciewicz, Hiramagular N. Jayaram

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Abstract

Purpose Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods A total of 10 6 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40x magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18). Conclusions Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.

Original languageEnglish
Pages (from-to)645-652
Number of pages8
JournalCardioVascular and Interventional Radiology
Volume35
Issue number3
DOIs
StatePublished - Jun 2012

Fingerprint

Hepatocellular Carcinoma
Rodentia
Apoptosis
Nonparametric Statistics
Neoplasms
Tumor Burden
Liver
3-(1-deoxyribofuranosyl)benzamide
DNA Nucleotidylexotransferase
Intravenous Administration
Sample Size
Sprague Dawley Rats
Therapeutics
Cell Line

Keywords

  • Cancer
  • Chemoembolization/ chemoembolization
  • Experimental IR
  • Hepatocellular carcinoma (HCC)
  • Interventional oncology
  • Liver/hepatic

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside. / McLennan, Gordon; Bennett, Stacy L.; Ju, Shenghong; Babsky, Andriy; Bansal, Navin; Shorten, Michelle L.; Levitin, Seth; Bonnac, Laurent; Panciewicz, Krystoff W.; Jayaram, Hiramagular N.

In: CardioVascular and Interventional Radiology, Vol. 35, No. 3, 06.2012, p. 645-652.

Research output: Contribution to journalArticle

McLennan, G, Bennett, SL, Ju, S, Babsky, A, Bansal, N, Shorten, ML, Levitin, S, Bonnac, L, Panciewicz, KW & Jayaram, HN 2012, 'Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside', CardioVascular and Interventional Radiology, vol. 35, no. 3, pp. 645-652. https://doi.org/10.1007/s00270-011-0140-z
McLennan, Gordon ; Bennett, Stacy L. ; Ju, Shenghong ; Babsky, Andriy ; Bansal, Navin ; Shorten, Michelle L. ; Levitin, Seth ; Bonnac, Laurent ; Panciewicz, Krystoff W. ; Jayaram, Hiramagular N. / Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside. In: CardioVascular and Interventional Radiology. 2012 ; Vol. 35, No. 3. pp. 645-652.
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abstract = "Purpose Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods A total of 10 6 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40x magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52{\%}; P = 0.18); IA BR and saline (44.49 vs. 33.83{\%}; P = 0.66); or IV BR and saline (1.52 vs. 193{\%}; P = 0.18). Conclusions Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.",
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T1 - Tumor response and apoptosis of N1-S1 rodent hepatomas in response to intra-arterial and intravenous benzamide riboside

AU - McLennan, Gordon

AU - Bennett, Stacy L.

AU - Ju, Shenghong

AU - Babsky, Andriy

AU - Bansal, Navin

AU - Shorten, Michelle L.

AU - Levitin, Seth

AU - Bonnac, Laurent

AU - Panciewicz, Krystoff W.

AU - Jayaram, Hiramagular N.

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N2 - Purpose Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods A total of 10 6 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40x magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18). Conclusions Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.

AB - Purpose Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods A total of 10 6 N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV). Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40x magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18). Conclusions Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.

KW - Cancer

KW - Chemoembolization/ chemoembolization

KW - Experimental IR

KW - Hepatocellular carcinoma (HCC)

KW - Interventional oncology

KW - Liver/hepatic

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