Submitted in complete fulfillment for the Degree of Doctor of Philosophy in Biotechnology, Durban University of Technology, Durban, South Africa, 2016. / Colon cancer is the third most common cancer worldwide with a high morbidity and mortality rate. Therapies are less effective during metastasis, therefore prevention and earlier detection is key to reducing the risk of colon cancer. Increased dietary fibre and probiotic intake is known to lower the risk of colon cancer. Probiotics are defined as “live microorganisms which when administered orally in an adequate amount confer a health benefit on the host”. The International Dairy Federation recommends a viable minimum level of 6–7 log10cfu/g in a probiotic product being consumed. Different biopolymer matrices have been used for encapsulation of probiotics; however, loss of viability is still a major challenge. Citrus pectin is a dietary fibre polysaccharide broken down into smaller fragments to form modified citrus pectin (MCP). The unique bioactivity of MCP against carcinogenesisis is linked to its sugar β-galactose inhibiting the cell signalling protein marker, galectin-3 (gal-3), which is intimately involved in endothelial cell morphogenesis. The vascular endothelial growth factor (VEGF) signalling, which invariably drives angiogenesis can be activated when gal-3 binds to integrins. The bioactivity and uptake of MCP may be improved through a novel approach if conjoined with a supplement for example probiotic. Therefore, the synergistic inhibitory effect of modified citrus pectin alginate (MCPA) probiotic microbeads on gal-3 and VEGF in an azoxymethane (AOM) induced colon carcinogenesis Balb/c mouse model was investigated. A microencapsulation process was used to produce a MCPA microbead containing probiotic, Lactobacillus acidophilus ATCC 4356. Efficiency of the microbead was evaluated in vitro (simulated conditions) and in vivo (Balb/c mouse model). Genomic identification of faecal lactobacilli samples from the treated mice was analyzed. Optimization of AOM dose-time with 10 and 15 mg/kg AOM intraperitoneal (ip) administered to Balb/c mice for 2 and 4 weeks were performed. The optimal AOM dose was initiated prior to intake of MCPA, AP (alginate calcium) probiotic microbeads and MCP in Balb/c mice for 16 weeks; samples were analyzed for colon histopathology and immunohistochemistry. The MCPA probiotic microbeads significantly enhanced the viability of L. acidophilus ATCC 4356 compared to the AP microbeads in vitro (p< 0.05). Exposure of the MCPA probiotic microbeads to 3 h of simulated gastric juice (SGJ) resulted in 82.7% survival of L. acidophilus ATCC 4356. Also, the faecal lactobacilli count in the MCPA probiotic treated mice significantly increased after 28 days by 10.2% compared to the AP probiotic, MCP treated and control mice (p< 0.0001). A total of 4DNA encoding 16S rRNA gene closest to the genera namely Lactobacillus, Bacillus, Enterococcus and Bifidobacterium were identified from faecal samples of the colon cancer-induced Balb/c mice. Azoxymethane at 15 mg/kg for 4 weeks induced optimal gal-3 and VEGF immunoexpression. Furthermore, MCPA probiotic treatment significantly reduced gal-3 immunoexpression in the colon of AOM induced cancer Balb/c mice compared to the control mice (p< 0.0001). The immunoexpresion of VEGF in the MCPA and AP probiotic treated groups was weakly positive and significantly reduced when compared to the control group (p<0.05), while the MCP treated group was barely positive (p< 0.001). Modified citrus pectin alginate is a novel effective means of oral delivery of bacterial cells and bioactive compounds. It has a good biodegradability, inexpensive, non-toxic, proven efficiency, and stability at low temperatures warranting its use as a drug carrier by pharmaceuticals. Modified citrus pectin alginate probiotic microbeads increase bioactivity and chemoprevention against colon pre-cancerous lesions and adenocarcinoma through inhibition of gal-3 and VEGF in the mouse model. Modified citrus pectin alginate can be used in probiotic therapy, which may improve the prevention of colon cancer. / D

Indiana University-Purdue University Indianapolis (IUPUI) / Given the numerous benefits of a healthy diet and exercise for cancer survivors, there has been an increase in the number of lifestyle intervention trials for this population in recent years. However, the extent to which adherence to a diet and exercise intervention predicts health-related outcomes among cancer survivors is currently unknown. To address this question, data from the Reach out to ENhancE Wellness in Older Cancer Survivors (RENEW) diet and exercise intervention trial were analyzed. RENEW was a yearlong telephone and mailed print intervention for 641 older (>65 years of age), overweight (body mass index: 25.0-39.9), long-term (>5 years post-diagnosis) survivors of colorectal, breast, and prostate cancer. Participants were randomized to the diet and exercise intervention or a delayed-intervention control condition. The RENEW telephone counseling sessions were based on determinants of behavior derived from Social Cognitive Theory (SCT) (e.g., building social support, enhancing self-efficacy). These factors have been hypothesized to improve health behaviors, which in turn should improve health outcomes. Thus, drawing on SCT and prior diet and exercise research with cancer survivors, I hypothesized that telephone counseling session attendance would be indirectly related to health-related outcomes (i.e., physical function, basic and advanced lower extremity function, mental health, and body mass index) through intervention-period strength and endurance exercise and dietary behavior (i.e., fruit and vegetable intake, saturated fat intake). The proposed model showed good fit to the data; however, not all of the hypothesized relationships were supported. Specifically, increased telephone counseling session attendance was related to engagement in all of the health behaviors over the intervention period. In turn, (a) increased endurance exercise was related to improvement in all of the health-related outcomes with the exception of mental health; (b) increased strength exercise was solely related to improved mental health; (c) increased fruit and vegetable intake was only related to improved basic lower extremity function; and (d) saturated fat intake was not related to any of the health-related outcomes. Taken together, these findings suggest that SCT determinants of behavior and the importance of session attendance should continue to be emphasized in diet and exercise interventions. Continued exploration of the relationship between adherence to a diet and exercise intervention and health-related outcomes will inform the development of more cost-effective and efficacious interventions for cancer and other medical populations.