Nutritional intervention in children undergoing chemotherapy for cancer

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2015-07-12
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Burkitt‘s lymphoma (BL) and Wilm‘s tumour (WT) are the two most common childhood cancers. BL is a malignant tumour of the B cells of the lymphoid tissues that affects mainly children in Africa and WT is a malignant tumour that develops in the kidney from nephroblast. For most cancers, chemotherapy is the main form of treatment but each step of the cancer continuum from diagnosis to recovery poses nutritional challenges. Poor nutritional status predisposes an individual to disease and makes disease progression faster and recovery slower; nutritional decline among cancer sufferers also decreases the effectiveness of treatment and can slow recovery. The study aim was to investigate the impact of high protein-based supplement on nutritional status, and recovery among children undergoing treatment for Burkitt‘s lymphoma and Wilms tumour treatment at the Komfo Anokye Teaching Hospital (KATH), Ghana and also to determine the anti-proliferative effects of Isoflavanoids isolated from soyabean (SB) and soyamilk powder (SMP) on Burkitt‘s lymphoma (DG 75) and other cell lines. The study was in 4 parts. In the first part, there was assessment of nutrient composition of the soymilk powder (SMP) used as a supplement. The second part, investigated the nutritional status of children suffering from cancer compared with an age and sex-matched non-cancer controls using a cross-sectional study design. The third part was a non-blinded randomized controlled trial of 32 children suffering from BL and WT who received soymilk powder (SMP) supplement and 32 non-supplemented cancer children. The intervention group was provided 2-weekly rations of the supplement measured to provide 80% RDA for protein for age and sex and were followed for 6 months, taking measurements at the 0, 3 and 6-months follow-up. During the follow-up nutritional status, some clinical parameters, deaths and recovery were monitored. Weight, height, mid-upper arm iv circumference (MUAC) and triceps skinfolds (TSF) were measured and wasting, underweight and stunting levels determined using World Health Organization (WHO) standards. Biochemical/hematological parameters measured were zinc, reduced glutathione, prealbumin and Hb. In the last part of the study, Isoflavones were isolated from soybean (SB) and soymilk powder (SMP) and the anti-proliferative effect of these isoflavones on Burkitt‘s lymphoma (DG-75) and leukemia (CEM) cell lines and prostrate normal cell lines (PNT 2) were investigated. Proximate analysis on the SMP revealed a protein concentration of 49.62% and was also found to be safe for consumption after microbial assessments. A total of 96 children (64 with cancer and 32 non cancer group) below the age of 15 years were enrolled for the second part. Repeated measure anova was used to compare differences between groups and p-value less that 0.05 was significant. With the exception of height, the cancer children had significantly lower weight (18.7 versus 27.4 kg; p<0.0001), MUAC (14.1 cm versus 17.8 cm; p<0.0001), TSF (4.9 cm versus 6.1 cm; p=0.0332), muscle arm circumference (MAC) (12.4 versus 15.8 cm; p<0.0001) and body mass index (BMI) (14.6 kg/m2 versus 18.4 kg/m2; p<0.0001). The cancer group had higher level of malnutrition by all indicators: Low BMI-for-age = 50%, stunting = 47%, wasting =31% and underweight = 34% compared to non-cancer controls (low BMI for age=4%, stunting = 25%, wasting= 8% and underweight= 7%). Among the cancer children 44% showed physical signs of wasting, 16% were oedematous and 44% had the sclera of the eye pale. The cancer group also had significantly lower levels of glutathione (p<0.0001) and prealbumin (p< 0.0001) than their non-cancer counterparts. SMP intervention improved the various anthropometric, biochemical/ hematological indices when the intervention group was more than the non-intervention group with height, weight and zinc being the exceptions. The SMP v intervention reduced low BMI- for-age by 39.4% and wasting by 25.6%. Anaemia was reduced by 84.2% in the intervention group and only 11.7% in the non-intervention group. Also, the percentage of children who were deficient in reduced glutathione improved by 21.9% in the intervention group compared to the 20.5% in the non-intervention group. In terms of recovery, the SMP improved recovery by 31%. In the final part of this work, the extract of isoflavones gave a higher concentration of genistein in SMP (5.5× 10-3 mg/ml) compared to 5.86× 10-4 mg/ml found in soyabean (SB). The concentration of daidzein in SMP was also higher (6.247× 10-3 mg/ml) than that found in SB (3.92× 10-4 mg/ml). The growth inhibitory effect of genistein on leukemia (CEM) cell line was stronger (IC50 = 767.5 mg/ml) than daidzein (IC50 = 2542.3 mg/ml). For the DG 75, genistein had an IC50 of 298.6 mg/ml and daidzein, IC50> 2542.3 mg/ml. The IC50 for SMP on DG-75 was 193.92 μg/ml and that for CEM, IC50= 54.17 μg/ml. In terms of selectivity index (SI) the SMP was able to prevent the proliferation of CEM and DG-75 than SB. In conclusion, this study revealed a high prevalence of undernutrition among cancer children compared to their non-cancer control. Nutrition supplementation using SMP improved the nutritional status of children with cancer. This is attributed to the higher protein, caloric and mineral composition of the SMP given to the intervention group. Furthermore, the anti-proliferative effect of isoflavanoids on lymphoma cell line DG-75 also suggest some level of anticancer activity of SMP.
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A thesis submitted to the Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology in partial fulfilment of the Requirements for the degree of DOCTOR OF PHILOSOPHY.
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