Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
Clinical Sciences
Non Technical Summary
Lymphoma is one of the most commonly diagnosed cancers in dogs and has a very high prevalence in some breeds. It has been reported to be the cause of death of 8% of all golden retrievers and to account for 11 -20% of cancer deaths in boxers, Labrador retrievers and German shepherd dogs. Current treatment protocols are successful at prolonging life, but are expensive, rarely result in a cure and can cause significant morbidity. Median survival time after diagnosis, even with treatment, is only 11-12 months and survival greater than two years has been reported to occur only in about 10% of dogs. Additional therapeutic targets are greatly needed to improve survival rates while limiting side effects and expense. If metabolic and dietary interventions could be identified to slow the progression of lymphoma, not only would this information advance our understanding of cancer in general, but it would also benefit a large number of dogs and could have applicability to humans as well. The project will contribute important information to the current body of knowledge on metabolic alterations in cancer and has the potential to lead to novel therapies.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
Hypothesis: IGF-1 concentrations will be higher in dogs with lymphoma than in normal control dogs. Lymphoma is one of the most common cancers diagnosed in dogs and has a very high prevalence in some breeds. It is important to enhance our understanding of the metabolic alterations that lead to and sustain tumorigenesis in order to develop additional therapeutic modalities. Nutritional strategies to support patients (both human and animal) during cancer therapy as well as novel diet-based treatment modalities are strongly in demand. Regulation of carbohydrate metabolism has been of interest to cancer researchers since the 1920s, when it was first discovered that many cancer cells utilize aerobic glycolysis rather than oxidative phosphorylation to produce energy. Studies have confirmed that dogs with various types of cancer have altered carbohydrate metabolism with higher serum concentrations of insulin and whole blood lactate concentrations than normal animals. Low carbohydrate diets have been advocated for dogs with cancer to help "starve" the cancer cells. Whether this diet strategy helps normalize carbohydrate metabolism in dogs with cancer has not been thoroughly investigated. One major piece of the carbohydrate metabolism puzzle that remains to be fully explored is insulin-like growth factor 1 (IGF-I), a peptide hormone related to insulin. It is produced in response to growth hormone (GH) and binds both the insulin receptor (low affinity) and its own receptor. Evidence is mounting that IGF-1 plays a direct role in tumorigenesis. In people, higher IGF-1 concentrations have been associated with increased risk of cancer. People with acute leukemia have also been shown to have higher concentrations of IGF-1. Similarly, a study in dogs with benign and malignant tumors demonstrated increased serum IGF-1 in dogs with malignant tumors versus normal dogs and those with benign masses. IGF-1 concentrations have not been evaluated in canine lymphoma nor have they been reported in the similar non-Hodgkins lymphoma of people. IGF-1, with its involvement in both carbohydrate metabolism and tumorigenesis, is a target of further investigation to better understand altered metabolic pathways in animals with cancer. IGF-1 receptor antagonists are currently being investigated in the treatment of some human cancers. This study seeks to measure serum IGF-1 concentrations in dogs with lymphoma as compared to healthy dogs.
Project Methods
Dogs with a first time diagnosis of multicentric lymphoma will be recruited to join a prospective, cross-sectional study. All enrolled dogs will have a body size equal to or greater than 25 kg body weight (to minimize variation in IGF-1 concentrations due to size differences21). Dogs must have been diagnosed with multicentric lymphoma on the basis of lymph node aspirate or biopsy and staged with complete blood count, serum chemistry panel, urinalysis, abdominal ultrasound, and thoracic radiographs and only dogs of substage a (subclinical) will be included. Healthy control dogs will be recruited and will be weight (+/- 10-15%), age (-1-/- 1 year), and sex matched with case dogs. After 5 weeks of therapy, an additional blood sample will be obtained (at which time all dogs should be in clinical remission).