The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer.
OBJECTIVE
Mucositis from cancer chemotherapy is a common problem for which there is no definitive treatment. It produces significant morbidity and occasional mortality. Prevention and successful treatment could significantly enhance the quality of life of patients, and improve survival; however any potential preventative agent must not enhance tumour growth. The aims of this study were to assess the effect of keratinocyte growth factor (KGF) on breast tumour growth, and in preventing small intestinal mucositis induced by methotrexate (MTX).


METHODS
Tumour-bearing rats received KGF or saline for 5 days prior to either MTX or saline treatment, and were killed 24 h after the last MTX injection. The weights of the tumour, small and large intestines, and liver were recorded. Apoptosis was assessed by TUNEL assay in the tumour and jejunum. Intestinal morphometry was used to assess villus area, crypt length and mitotic crypt count. Tumour proliferation was assessed by mitotic count.


RESULTS
KGF increased the weight of the small intestine prior to chemotherapy but the weight was not maintained after chemotherapy. KGF synergized with MTX to increase apoptosis in both intestinal crypts and the breast cancer. KGF also reduced tumour size.


CONCLUSIONS
We conclude that KGF had a modest effect on intestinal growth prior to chemotherapy. It did not protect the gut from mucositis, nor did it worsen morphometry. It reduced tumour size.
Department of Gastroenterology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
Rachel J
RJ
Gibson
Dorothy M K
DM
Keefe
Julie M
JM
Clarke
Geoff O
GO
Regester
Fiona M
FM
Thompson
Gary J
GJ
Goland
Ben G
BG
Edwards
Adrian G
AG
Cummins
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000009:adverse effects; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate
D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; C496455:Fgf7 protein, rat; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D008727:Methotrexate