Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1

Steven G. Fukuchi, Jeffrey L. Seeburger, Guido Parquet, Rolando Rolandelli

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-β1 (TGF- β1) is normally upregulated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-β1. Materials and methods. Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg x s) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-β1 normalized to that of a constitutive gene. Results. Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 ± 7.6 vs 161.1 ± 7.2 and 139.9 ± 10.9 vs 186.0 ± 8.6; BE, 1093.6 ± 190.0 vs 2207.9 ± 308.2, and 1518.5 ± 326.5 vs 3279.3 ± 225.7, respectively. Anastomotic TGF-β1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 ± 0.05 vs 0.84 ± 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF- β1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration. Conclusions. Wound healing following a colonic anastomosis is associated with local increases in TGF-β, expression, which in turn is diminished by the administration of 5- FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.

Original languageEnglish (US)
Pages (from-to)121-126
Number of pages6
JournalJournal of Surgical Research
Volume84
Issue number2
DOIs
StatePublished - Jun 15 1999
Externally publishedYes

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Fluorouracil
Transforming Growth Factor beta
Wound Healing
Transforming Growth Factors
Postoperative Period
Descending Colon
Reverse Transcriptase Polymerase Chain Reaction
Sprague Dawley Rats
Colon
Pressure
Recurrence
Drug Therapy
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Fukuchi, Steven G. ; Seeburger, Jeffrey L. ; Parquet, Guido ; Rolandelli, Rolando. / Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1. In: Journal of Surgical Research. 1999 ; Vol. 84, No. 2. pp. 121-126.
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title = "Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1",
abstract = "Background. Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-β1 (TGF- β1) is normally upregulated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-β1. Materials and methods. Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg x s) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-β1 normalized to that of a constitutive gene. Results. Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 ± 7.6 vs 161.1 ± 7.2 and 139.9 ± 10.9 vs 186.0 ± 8.6; BE, 1093.6 ± 190.0 vs 2207.9 ± 308.2, and 1518.5 ± 326.5 vs 3279.3 ± 225.7, respectively. Anastomotic TGF-β1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 ± 0.05 vs 0.84 ± 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF- β1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration. Conclusions. Wound healing following a colonic anastomosis is associated with local increases in TGF-β, expression, which in turn is diminished by the administration of 5- FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.",
author = "Fukuchi, {Steven G.} and Seeburger, {Jeffrey L.} and Guido Parquet and Rolando Rolandelli",
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Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1. / Fukuchi, Steven G.; Seeburger, Jeffrey L.; Parquet, Guido; Rolandelli, Rolando.

In: Journal of Surgical Research, Vol. 84, No. 2, 15.06.1999, p. 121-126.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Influence of 5-fluorouracil on colonic healing and expression of transforming growth factor-beta 1

AU - Fukuchi, Steven G.

AU - Seeburger, Jeffrey L.

AU - Parquet, Guido

AU - Rolandelli, Rolando

PY - 1999/6/15

Y1 - 1999/6/15

N2 - Background. Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-β1 (TGF- β1) is normally upregulated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-β1. Materials and methods. Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg x s) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-β1 normalized to that of a constitutive gene. Results. Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 ± 7.6 vs 161.1 ± 7.2 and 139.9 ± 10.9 vs 186.0 ± 8.6; BE, 1093.6 ± 190.0 vs 2207.9 ± 308.2, and 1518.5 ± 326.5 vs 3279.3 ± 225.7, respectively. Anastomotic TGF-β1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 ± 0.05 vs 0.84 ± 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF- β1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration. Conclusions. Wound healing following a colonic anastomosis is associated with local increases in TGF-β, expression, which in turn is diminished by the administration of 5- FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.

AB - Background. Administration of chemotherapeutic agents in the immediate postoperative period may have beneficial effects by decreasing local cancer recurrence rates, but this must be weighed against possible impairment of wound healing. Since local expression of transforming growth factor-β1 (TGF- β1) is normally upregulated following creation of experimental colonic anastomoses, this study examines the effects of 5-fluorouracil (5-FU) on colonic healing and on the local expression of TGF-β1. Materials and methods. Forty-eight male Sprague-Dawley rats underwent transection of the descending colon with primary anastomosis and were then randomly assigned to receive either intraperitoneal 5-FU (20 mg/kg/day) or saline (SAL). On Postoperative Days (PODs) 3, 5, and 7, bursting pressure (BP, mm Hg) and bursting energy (BE, mm Hg x s) were determined in situ. Anastomotic and nonoperated segments of colon were harvested and analyzed using the semiquantitative reverse transcriptase-polymerase chain reaction to determine the relative expression of TGF-β1 normalized to that of a constitutive gene. Results. Progressive increases in BP and BE were observed in both the 5-FU and the SAL groups, across the time course examined. Overall, these measures were decreased in the 5-FU groups compared to SAL, significantly so on PODs 5 and 7; BP, 127.8 ± 7.6 vs 161.1 ± 7.2 and 139.9 ± 10.9 vs 186.0 ± 8.6; BE, 1093.6 ± 190.0 vs 2207.9 ± 308.2, and 1518.5 ± 326.5 vs 3279.3 ± 225.7, respectively. Anastomotic TGF-β1 expression also increased progressively in both groups over the postoperative time course. Expression in the 5-FU group, however, was significantly decreased compared to that in the SAL group on POD 3; 0.42 ± 0.05 vs 0.84 ± 0.04. Interestingly, this preceded the reduction in BP and BE in the 5-FU group on PODs 5 and 7. TGF- β1 expression in nonoperated colonic segments did not change during the time points studied or in response to 5-FU administration. Conclusions. Wound healing following a colonic anastomosis is associated with local increases in TGF-β, expression, which in turn is diminished by the administration of 5- FU. If this deleterious effect on wound healing could be counteracted, then chemotherapy administration in the immediate postoperative period may become safer.

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