The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer

Gibson, Rachel J.; Keefe, Dorothy; Clarke, Jane; Regester, Geoff; Thompson, Fiona M.; Goland, Gary J.; Edwards, Ben; Cummins, Adrian G.

doi:10.1007/s00280-002-0460-4

Cited by 88 publications

(66 citation statements)

References 12 publications

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“…8,23,24 This tumor is specific to the DA rat. Tumor-bearing animals were used in this study to ensure that palifermin did not promote tumor growth or interfere with the cytotoxicity of irinotecan.…”

Section: Passage Of Tumormentioning

confidence: 99%

“…The method used to stain for apoptosis was performed using the In Situ Cell Death Detection Kit AP (Roche, Mannheim, Germany) and has been described elsewhere. 2,8,[23][24][25] Briefly, slides were dewaxed and rehydrated through graded ethanols prior to immersion in a 0.1% TX-100 in 0.1% (w/v) sodium citrate buffer solution for 8 min at room temperature. After 2 washes in PBS, slides were placed in a TUNEL buffer solution (150 mM Tris, 0.7M NaCaCo, 10 mM CoCL 2 , 10% BSA, sterile H 2 0) for 10 min at room temperature.…”

Section: Apoptosis Assessmentmentioning

confidence: 99%

“…Microdissected tissue was mounted in 45% (w/v) acetic acid and measurements were taken using a calibrated graticule of the villus length, apical and basal widths of 15 villi (jejunum) and the lengths of 15 crypts (jejunum and colon). 2,8,[23][24][25] Villus area was calculated using a trapezoid approximation with villus area and crypt length correlating with villus and crypt epithelial cell populations, respectively. 2,8,[23][24][25] All assessments were conducted in a blinded fashion by 2 investigators (R.J.G.…”

Section: Intestinal Morphometrymentioning

confidence: 99%

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Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Gibson

Bowen

Keefe

2005

Intl Journal of Cancer

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Mucositis is a common side effect of cancer chemotherapy for which there is currently no treatment. Irinotecan is a commonly used effective chemotherapeutic agent, causing severe gastrointestinal mucositis and diarrhea. Previous research suggests that palifermin is potentially antimucotoxic. The primary aim of this study was to determine whether palifermin was effective in ameliorating irinotecan-induced gastrointestinal mucositis. We also determined the protective effects of single large and multiple small doses of palifermin. Tumor-bearing DA rats were treated with a single large (10 mg/kg) dose of palifermin 3 days prior to, or multiple small (3 mg/kg day for 3 days) doses of palifermin or vehicle control prior to, receiving 2 doses of 150 mg/kg irinotecan. Animals were killed at 6, 24, 48, 72, 96, 120, or 144 hr after treatment. The primary endpoints were diarrhea and mortality. Gastrointestinal morphometry, histopathology and apoptosis were assessed. Tumor weights and mitoses were measured to ensure palifermin did not promote tumor growth. Data were analyzed using Peritz' F-test, Student's t-test and Tukey-Kramer multiple comparison test. Animals pretreated with palifermin tolerated irinotecan treatment better than control animals with less severe diarrhea (5% in animals receiving 10 mg/kg palifermin, 11% in animals receiving 3 3 3 mg/kg palifermin and 28% in animals receiving irinotecan only) and reduced mortality (2% in animals receiving 10 mg/kg palifermin, 11% in animals receiving 3 3 3 mg/kg palifermin and 28% in animals receiving irinotecan only). Small and large intestinal weights were maintained. Intestinal morphometry was not maintained in palifermin-pretreated rats despite being increased prior to irinotecan treatment. Palifermin pretreatment did not prevent apoptosis that peaked at 6 hr in the jejunum or colon, but prevented apoptosis at 96 hr in the small intestine. Palifermin pretreatment in both treatment regimens significantly reduces diarrhea and mortality following irinotecan administration without adversely affecting tumor growth. This positive response warrants further investigation, particularly in humans. ' 2005 Wiley-Liss, Inc.Key words: mucositis; irinotecan; palifermin; diarrhea Mucositis is a major oncologic problem caused by the cytotoxic effects of cancer chemotherapy. The condition affects the entire gastrointestinal tract from the mouth to the anus and causes pain and ulceration in both the mouth and small and large intestines. In addition, it causes abdominal bloating, vomiting and diarrhea.

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Section: Passage Of Tumormentioning

confidence: 99%

Section: Apoptosis Assessmentmentioning

confidence: 99%

Section: Intestinal Morphometrymentioning

confidence: 99%

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Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Gibson

Bowen

Keefe

2005

Intl Journal of Cancer

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“…All rats received breast cancer inoculum as described previously. 49,50 Briefly, mammary adenocarcinoma tumors syngeneic with the DA rat were diced, homogenized and filtered through sterile gauze. A viable cell count was conducted using 0.4% w/v trypan blue before 150 μl of cells were implanted subcutaneously into both right and left flanks of the rat at a concentration of 2.0 × 10 7 cells/mL.…”

Section: Experimental Designmentioning

confidence: 99%

Irinotecan disrupts tight junction proteins within the gut

Wardill

Bowen

Al‐Dasooqi

et al. 2013

Cancer Biology & Therapy

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“…Data from animal models 24,25 showed that KGF treatment is effective in the prevention of intestinal mucositis. KGF is produced by mesenchymal cells and is a member of the fibroblast growth factor (FGF) superfamily.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study

Tsirigotis

Triantafyllou

Girkas

et al. 2008

Bone Marrow Transplant

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The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer

Abstract: 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.

Cited by 88 publications

References 12 publications

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Irinotecan disrupts tight junction proteins within the gut

Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study

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