TY - BOOK
T1 - Nutrition and Gut Mucositis in Pediatric Oncology
AU - Pontoppidan, Peter Erik Lotko
N1 - CURIS 2015 NEXS 173
PY - 2015
Y1 - 2015
N2 - Childhood malignancies are the second most common cause of death in children. A major limitation of current therapies is the high toxicity. Alimentary tract toxicity (mucositis) is associated with increased risk of complication such as infections that may lead to death. In relation to HSCT, mucositis is believed to be an important driver in development of graft versus host disease (GVHD). Thus effective treatment strategies against mucositis can increase survival by preventing severe infections and indirectly by allowing for treatment intensification against resistant malignancies. Unfortunately, effective treatment strategies against mucositis are not in general available. The overall aim of the present PhD was to study interactions between mucositis, inflammation and nutrition. We hypothesized that toxic reactions in the alimentary tract, induced by chemotherapy, followed by release of inflammatory mediators contribute to the development of mucositis. Further we hypothesized that intestinal toxicity is diet-dependent. Specifically, we hypothesized that bovine colostrum (BC) would mitigate mucositis compared with a milk replacer (MR). In paper I we aimed to induce mucositis in piglets evident as oral ulcers and reduced intestinal weight and villus height in the small intestine in chemotherapy-treated piglets, compared with saline controls. In paper II, we showed that BC feeding preserved intestinal functions during chemotherapy in piglets, however here was no effect on structural signs of intestinal mucositis. In paper III, we investigated development of oral mucositis and intestinal mucositis in children along with circulatory markers of inflammation and leukocyte function during the first month after HSCT. Intestinal mucositis was accompanied by release of pro-inflammatory cytokines and differential regulation of miRNA-155 and -146a. This was sustained during the first three weeks after transplantation, along with increased spontaneous production of inflammatory cytokines by early trafficking of leukocytes. In conclusion, we successfully induced oral and intestinal mucositis in piglets and showed that bovine colostrum helps to preserve intestinal function during chemotherapy-induced mucositis although it has no effect on structural signs of mucositis. The anti-mucositis potential of bovine colostrum should be investigated further with regards to its dose and timing in relation to chemotherapy treatment. Finally, we showed that mucositis in children is associated with a proinflammatory systemic response and a differential regulation of miRNA that is sustained during the first three weeks following the transplantation.
AB - Childhood malignancies are the second most common cause of death in children. A major limitation of current therapies is the high toxicity. Alimentary tract toxicity (mucositis) is associated with increased risk of complication such as infections that may lead to death. In relation to HSCT, mucositis is believed to be an important driver in development of graft versus host disease (GVHD). Thus effective treatment strategies against mucositis can increase survival by preventing severe infections and indirectly by allowing for treatment intensification against resistant malignancies. Unfortunately, effective treatment strategies against mucositis are not in general available. The overall aim of the present PhD was to study interactions between mucositis, inflammation and nutrition. We hypothesized that toxic reactions in the alimentary tract, induced by chemotherapy, followed by release of inflammatory mediators contribute to the development of mucositis. Further we hypothesized that intestinal toxicity is diet-dependent. Specifically, we hypothesized that bovine colostrum (BC) would mitigate mucositis compared with a milk replacer (MR). In paper I we aimed to induce mucositis in piglets evident as oral ulcers and reduced intestinal weight and villus height in the small intestine in chemotherapy-treated piglets, compared with saline controls. In paper II, we showed that BC feeding preserved intestinal functions during chemotherapy in piglets, however here was no effect on structural signs of intestinal mucositis. In paper III, we investigated development of oral mucositis and intestinal mucositis in children along with circulatory markers of inflammation and leukocyte function during the first month after HSCT. Intestinal mucositis was accompanied by release of pro-inflammatory cytokines and differential regulation of miRNA-155 and -146a. This was sustained during the first three weeks after transplantation, along with increased spontaneous production of inflammatory cytokines by early trafficking of leukocytes. In conclusion, we successfully induced oral and intestinal mucositis in piglets and showed that bovine colostrum helps to preserve intestinal function during chemotherapy-induced mucositis although it has no effect on structural signs of mucositis. The anti-mucositis potential of bovine colostrum should be investigated further with regards to its dose and timing in relation to chemotherapy treatment. Finally, we showed that mucositis in children is associated with a proinflammatory systemic response and a differential regulation of miRNA that is sustained during the first three weeks following the transplantation.
UR - https://rex.kb.dk/primo-explore/fulldisplay?docid=KGL01009154519&context=L&vid=NUI&search_scope=KGL&tab=default_tab&lang=da_DK
M3 - Ph.D. thesis
SN - 978-87-7611-884-6
BT - Nutrition and Gut Mucositis in Pediatric Oncology
PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
CY - Copenhagen
ER -