Background Colorectal cancer is becoming the commonest cancer in Hong Kong in 2011. Colorectal cancer screening is becoming a hot topic of discussion after the proposal of a local pilot screening program of colorectal cancer in the Policy Address 2014. Colorectal screening is traditionally performed by faecal occult blood test and optical colonoscopy. Computed tomographic colonography is a new imaging technology, with high sensitivity and specificity for clinically significant colonic lesions and polyps. It is therefore emerging as a new method for the colorectal cancer screening. Method This project aims to systemically review the literature, try to explore the potential utility and cost effectiveness of using computed tomographic colonography as one of the screening modality for asymptomatic patients aged 50 years or older. Results and Conclusion The results of the review are presented and conclusion is made. The limitation of the systematic review and its implications of local policy making are also discussed. / published_or_final_version / Public Health / Master / Master of Public Health

This thesis describes a three year study which explored perceptions and experiences of being involved in self care and perceptions of control and self-efficacy over time amongst patients receiving a six month course of chemotherapy treatment for colorectal cancer. The study was underpinned by Leventhal’s Self Regulation Model and aimed to explore how patients undergoing chemotherapy for colorectal cancer perceived the meaning of self care, what they did as part of their self care in managing the effects of their treatment and whether this changed between the beginning and end of their six month course of chemotherapy. The study also set out to explore the relationship between patients’ perceptions of control and self efficacy and their involvement in self care. The study adopted a patient focussed, mixed method, longitudinal approach for complementarity and expansion purposes in which the qualitative findings formed the focus of the investigation, supplemented by the quantitative findings. This was important to provide a greater breadth and range to the study and to obtain a realistic understanding of patients’ perceptions and experiences of being involved in self care during their six month course of chemotherapy treatment and the influence of their perceptions of control and self efficacy on their involvement in self care. Thirty one patients participated in the study and data were collected using qualitative semi structured interviews (with a subsample of patients who participated in the study) and quantitative questionnaires (Illness Perception Questionnaire-revised and the Strategies Used by People to Promote Health) and prospective self care diaries with the full study sample. Data were collected at several time points over the course of patients’ chemotherapy treatment (beginning, middle and end of treatment) and were analysed and integrated in accordance with Tashakkori and Teddlie (1998)’s guidance for integrating qualitative and quantitative findings in a mixed methods study. The study findings revealed that the use of a mixed method, longitudinal study design was a valuable approach for understanding patients’ involvement in self care during chemotherapy for colorectal cancer and the influence of factors, such as their perceptions of control, on their subsequent involvement in their self care. In particular, the principal findings suggested that self care held a range of meanings to the patients in this study. Principally, patients’ self care consisted of two components; physical self care, carried out to manage the physical impact of undergoing treatment, and emotional self care, carried out to manage their emotional response to being diagnosed with, and undergoing treatment for, cancer. The findings suggested that there was no association between patients’ perceptions of control and the degree of self care that they carried out identified in the quantitative analysis. However, in the qualitative analysis, it was revealed that patients’ perceptions of control were likely to influence their attitudes towards their active involvement in self care and the importance with which they viewed this role. In particular, patients who considered themselves to have a high degree of control during their treatment were more likely to believe that they could limit the impact of the treatment through their own actions, that being actively involved in their self care was important and were interested in taking on this role, and that they would use a greater range of self care strategies in helping to manage the impact of their treatment. Conversely patients who considered themselves to have a lower degree of control during their treatment were less likely to believe that they could limit the impact of the treatment through their own actions, that their active involvement in self care was important and were less likely to expect to take on an active role, preferring to leave the management of treatment-related effects to health professionals, whom they regarded as being the “experts”. The findings from this study have implications for nursing practice because they reinforce the importance of the listening to the patient’s experience and how this approach can contribute to a fuller and more accurate understanding of how patients become involved in their self care and the factors that influence this. This is important so that nurses can provide holistic care, tailored to meet their patients’ self care needs and preferences, and to encourage partnership working between patients, nurses, allied health professionals and other agencies in promoting involvement in self care. The findings also have implications for theories relating to self care in emphasising the importance of patient centred models of care and for Leventhal’s Self Regulation Model in adding further support for the components of the model yet also offering a greater understanding of how the model fits with patients’ emotional responses to the effects of illness and its’ treatments. Finally, the study findings have implications for future research, calling for further research to focus on the meaning of constructs such as self care and control from the patients’ perspective and to further explore the use of the mixed methodology in researching and understanding patients’ involvement in self care and the factors that influence this.

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

Folate deficiency, a prevalent vitamin deficiency in America, can stem from environmental and/or genetic causes. The most common inborn error of folate metabolism is deficiency of methylenetetrahydrofolate reductase (MTHFR), which catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Severe MTHFR deficiency results in hyperhomocysteinemia and homocystinuria; patients present with developmental delay, and various neurological and vascular disorders. This thesis describes three mutations identified in the MTHFR locus in patients with severe deficiency: 1025T→C (M→T), 1027T→G (W→G), and 1768G→A (E→K). Genotype-phenotype correlations are described, along with biochemical characterization of three mutations (983A→G (N→S), 1025T→C, 1027T→G). All three mutations exert their effect by decreasing Vmax without changing the enzyme's affinity for its substrate, 5-methyltetrahydrofolate. The 983A→G variant also conferred decreased affinity for FAD, a cofactor. / The more common and mild deficiency observed in the general healthy population is probably due in part to insufficient dietary intake of folate. Folate deficiency has been associated with increased risk for colon cancer. In a pilot study presented here, the impact of altered folate intake on tumor multiplicity in the Min mouse, a model for multiple intestinal neoplasia, was assessed. Folate deficient diets did not produce a consistent change in tumor numbers. However, a linear correlation between S-adenosylmethionine and S-adenosylhomocysteine content of preneoplastic tissue and tumor multiplicity was identified. / This thesis contributes to our understanding of the impact of genetic- and/or dietary-induced folate deficiency on cellular and organismal functions.

Dietary factors have been implicated in the etiology of colon cancer. The salient components of high-risk diets are thought to be high intakes of meat, especially beef, and fat, especially animal fat, and low intakes of fiber. Low-risk diets are thought to be high in fiber, and low in meat and animal fat. The present study examines the effects of short-term consumption of diets hypothesized to increase or decrease the risk for colon cancer on mutagenic activity of feces. Whether the fecal mutagens responsible for the mutagenic activity observed in the study are directly involved in the etiology of colon cancer is not known. However, most known mutagens are potentially carcinogenic, and fecal mutagenic activity may be an indicator of risk for colon cancer. Six healthy adult subjects consumed the following diets in sequence a baseline diet for one week, a low-risk lacto-ovo vegetarian, high fiber diet for two weeks, and a high-risk, high meat, low fiber diet for two weeks. Quantitative daily food intake records were kept, and daily bowel habits were recorded. Fecal samples were collected at the end of each diet period. Analyses were performed of the diets for food and nutrient intake, and of feces for percent dry weight and pH. Mutagenic activity of the fecal samples was assayed using the fluctuation test for mutagens. The subjects' habitual diets, although omnivorous, were found to closely resemble a low-risk diet pattern. Analysis of the vegetarian and high meat diets confirmed that the subjects had consumed foods which respectively represented the components of high-risk and low-risk diets. The overall fecal mutagenic activity obtained with samples on the high meat diet was higher than with the vegetarian or baseline diets using Salmonella typhimurium TA 98 and TA 100. The trend towards higher mutagenicity on the high meat diet over the vegetarian diet was consistent for all six subjects using TA 100, and for five of the six using TA 98. The vegetarian and baseline diets resulted in similar overall mutagenic activity. Analysis of the fecal sample parameters using the Kruskal-Wallis one-way analysis of variance showed no significant differences among fecal samples from the three diet periods with respect to wet weight, dry weight, percent dry weight, pH or number of daily bowel movements. However, a sign-test analysis showed a significant trend (p<0.05) towards fewer bowel movements on the high meat diet than on the vegetarian diet. There were significant differences among subjects for all of the fecal sample parameters (p<0.01 or p<0.001). Spearman rank correlations were significantly positive between mutagenic activities using bacterial strains Salmonella typhimurium TA 98 and TA 100 for the baseline diet (p<0.01) and the vegetarian diet (p<0.05). There were also significant positive correlations (p<0.001) between pH and fecal mutagenicity on the high meat' diet using tester strain TA 100, and between wet weight and dry weight. The results of this study indicate that the overall mutagenic activity of human feces can be increased over a period of two weeks by the consumption of a diet high in meat and low in fiber, which is considered to be a high-risk diet for colon cancer. / Land and Food Systems, Faculty of / Graduate

Mutagens in feces have been suggested to be an indicator for risk of colon cancer. Groups consuming vegetarian diets are known to have lower mortality from colon cancer. The purpose of this study was to assess mutagenic activity in feces of persons habitually consuming vegetarian or non-vegetarian diets and to try to identify dietary factors or other health habits which contributed to fecal mutagenicity. Eleven strict vegetarians, six ovo-lacto vegetarians and twelve non-vegetarians, all from the Greater Vancouver area, participated in this study. Data on certain demographic variables and health habits, as well as dietary intake (food frequency and food records), were taken. One fecal sample was collected from each subject for the study. Aqueous extracts of the feces were prepared and analyzed for mutagens using the fluctuation test with Salmonella typhimurium TA100 and TA98. Levels of mutagenicity on each organism were then statistically correlated with frequency of consumption of food groups, nutrient intake, demographic data and health habits. Ovo-lacto vegetarians and strict vegetarians, as groups, had significantly lower levels of fecal mutagens than non-vegetarians in the TA100 assay. With TA98, only the strict vegetarians had lower levels of mutagens compared to the non-vegetarians. The presence of several different mutagenic compounds was indicated. Significant negative correlations were found with mutagenicity on TA98 for all subjects with the following dietary variables: fruits and juices, fiber and iron. Similar negative correlations were found for total carbohydrate and Southgate fiber intakes and mutagenicity on TA100. Within the group of non-vegetarians, there were negative correlations with mutagenicity on TA98 and total protein and with mutagenicity on TA100 and calcium. With the demographic variables and health habits, no clear pattern emerged to indicate factors which would predict lowered mutagenicity for all subjects. It is concluded that vegetarians have lower levels of fecal mutagenicity and that several dietary factors are likely to contribute to this phenomenon. / Land and Food Systems, Faculty of / Graduate

The water solubility of drug molecules plays an important role in consideration of formulation development to treat a wide range of diseases. In this project, two kinds of drug delivery systems, cyclodextrins and liposomes, were developed for insoluble drug delivery to treat Alzheimer's disease (AD) and colorectal cancer (CRC), respectively. AD is an irreversible neurodegenerative disorder associated with the accumulation of amyloid-beta (A??) fibrils. Approximately 10% of people aged 65 and above have AD. Crocetin (CRT) is an active compound isolated from the fruits of gardenia (Gardenia jasminoides Ellis) and the stigmas of saffron (Crocus sativus L.). It has been reported to show various neuroprotective activities. However, poor water solubility and bioavailability are the major obstacles in developing pharmaceutical formulations of CRT. To address the issues, CRT liposomal formulations and CRT-cyclodextrin inclusion complexes were developed and evaluated. CRT-cyclodextrin inclusion complexes significantly increased the water solubility of CRT from the range ??g/mL to mg/mL. The CRT-??-cyclodextrin inclusion complex (1:3 molar ratio of CRT/??-cyclodextrin) was chosen for further studies as it showed the highest encapsulation efficiency (94.73 ?? 0.86%). The formulation had no toxicity to neuronal cells nor AD model cells within the experimental concentration range (0.625 to 100 ??M of CRT). It could downregulate the expression of C-terminus fragments and decrease both intracellular and extracellular levels of A??, which are hallmarks of AD. It also showed dose-dependent neuroprotective and antioxidant effects against H2O2-induced cell death. Pharmacokinetics and biodistribution studies showed that this CRT-??-cyclodextrin inclusion complex was suitable for intravenous administration. The formulation significantly increased the bioavailability of CRT and facilitated CRT crossing the blood-brain barrier to enter the brain. Similar to AD, CRC is increasingly prevalent with aging populations. Approximately 60% of CRC patients are aged 70 and above. Halofuginone (HF) is an active pharmaceutical ingredient (API) originated from Chinese quinine (Dichroa febrifuga Lour.) and artesunate (ART) is a semi-synthetic derivative of artemisinin (ATS) extracted from annual wormwood (Artemisia annua L.). Both APIs show anticancer activities by inhibiting the growth of CRC. However, low aqueous stability limits their applications. Liposome formulation with surface functionalization by CPP2 cell-penetrating peptide was developed to deliver HF and ART for targeted CRC therapy. CPP2 is a peptide that can selectively penetrate colon cancer cells. The liposomal drug formulations had uniform particle size (about 100 nm), high encapsulation efficiency (over 80%) and good stability upon 14 days of storage. In cellular uptake study, CPP2-modified liposome showed stronger permeability and selectivity to colon cancer lines without inducing lysosomal degradation. CPP2 surface-modified liposomal drugs demonstrated greater anticancer activities than free form of drugs or conventional liposomal drugs. Combinations of HF and ART formulations notably decreased cancer cell viability as compared to single formulation alone, which indicated that HF and ART formulations exhibited synergistic anticancer effects at specific ratios. To conclude, the drug delivery systems, cyclodextrins and peptide-modified liposomes, which were developed for AD and CRC treatment, successfully improved the aqueous solubility of insoluble APIs extracted from Chinese medicinal plants.

Thesis (Ph.D. (Biochemistry)) -- University of Limpopo, 2021 / Cancer remains one of the leading causes of morbidity and mortality worldwide with an estimated 9.9 million deaths in 2020. Cancer treatment regimens such as chemotherapy and radiotherapy have over the years fallen short due to drug resistance, toxicity, damage to normal healthy cells and tissues surrounding the treatment area. Moreover, they have shown very limited survival benefits for most advanced staged cancers such as colorectal cancer, which in 2020 was responsible for 3 728 deaths with a 6.8% incidence rate. Despite the many efforts in developing alternative chemotherapeutic strategies, cancer of the colon and cancer, in general, remains a burden. For centuries, plants and plant derivatives have been exploited for their nutritional and medicinal properties and now serve as chemical scaffolds or templates for designing and synthesising products with pharmacological importance. Herbal medicines are claimed to enhance therapeutic effects and are often used in combination with chronic medication. However, the concurrent use of herbal medicines and synthetic drugs may affect the pharmacokinetic profile of therapeutic drugs or trigger unexpected and undesirable effects. This study aimed to characterise the leaf extracts (crude water and crude methanol) of Momordica balsamina and investigate their potential anticancer activity on HT-29 colon cancer cells. The study also aimed to asses the effect of the extracts on drug metabolising enzymes (CYP450), specifically those which metabolise 5-Fluorouracil (5-FU) prodrugs or are inhibited by 5-FU since it is one of the first-line treatments for colon cancer. Dried powdered leaves were extracted using water and absolute methanol to obtain crude water and crude methanol extracts, respectively. For characterisation, the extracts were spotted on thin-layer chromatography (TLC) plates and further screened using chemical tests. The ferric ion reducing power assay and Liquid chromatographymass spectrometry were used to determine the antioxidant activity of the extracts and to identify prominent or abundant compounds in each extract, respectively. To assess the cytotoxic effect of the extracts and 5-FU, HT-29 colon cancer cells and C2C12 muscle cells, which were used as a model for normal cells, were exposed to concentrations that ranged from 0 to 2000 µg/ml for the water (H2O) extract, 0 to 300 µg/ml for the methanol (MeOH) extract or 0 to 100 µg/ml of 5-FU for 24 and 72 hours, and subjected to the MTT assay. The effect of the extracts on the efficacy of 5-FU was xxi assessed using the MTT assay by combined treatments of the extract and 5-FU. Genotoxicity of the extracts was assessed on the C2C12 cells using the Muse™ MultiColour DNA Damage kit. The generation of intracellular reactive oxygen species (ROS) was assessed by flow cytometry using the DCFH-DA assay. The JC-1 and acridine orange (AO)/propidium iodide (PI) staining assays were used to assess the effect of the extracts on the mitochondrial potential as well as cell and nuclear morphology, respectively. Apoptosis was quantified by flow cytometry using annexin V/PI and caspase activation assessed using the Caspase-8 and Caspase-9 colourimetric assay kits. The pro-apoptotic mechanism(s) was determined by assessing the expression profiles of selected apoptosis regulatory proteins using the human apoptosis antibody array kit. Cell cycle analysis by flow cytometry was conducted to determine the effect of the extract on the cell division cycle. Moreover, to determine the potential of herb-drug interactions, the Vivid® CYP450 Screening kits and P-gp-GloTM Assay Systems with P-glycoprotein were used to assess the effect on the activity of drug metabolising enzymes and drug transportation, respectively. The results showed that the MeOH extract possessed fewer polar compounds, higher ferric iron-reducing power, and a relative abundance of flavonol glycosides, cucurbitane-type triterpenoid aglycones, and cucurbitane-type glycosides than the H2O extract. The MeOH extract was further selectively cytotoxic to the HT-29 colon cancer cells at 24 hours of treatment and selectively induced genotoxicity in HT-29 cells. The H2O extract, however, was not cytotoxic to the HT-29 cells at all the tested concentrations at 24 and 72 hours of treatment. Analysis of nuclear and cell morphology suggested that the decrease in the percentage viability of MeOH extracttreated cells was associated with apoptotic cell death. Apoptosis was further confirmed by the loss of mitochondrial potential, increase in ROS production, caspase-8 and -9 activities as well as Annexin-V/PI-stained cells. Cell cycle analysis revealed cell cycle arrest at the S phase in MeOH extract-treated cells. Analysis of protein expression profiles revealed that the extract modulated various proteins that play a role in the promotion or inhibition of apoptosis. Moreover, the MeOH extract was shown to inhibit the activity of CYPs 1A2, 2A6, 2C8, and 2C9, while the H2O extract showed no significant inhibitory effects on the activity of all tested CYPs and 5-FU only significantly inhibited the activity of CYP2C9. However, combinatory treatments with 5-FU and the MeOH extract were shown to have no additive or diminishing effects on the efficacy of 5-FU on the activity of all the tested CYP enzymes. Treatment with 5FU (0.008 – 32 μg/ml) and the H2O extract (0.02 – 200 μg/ml) was shown to stimulate the ATPase activity of P-gp, while the MeOH extract significantly inhibited its activity with concentrations of 0.2, 2, and 20 μg/ml. In conclusion, the MeOH extract selectively induced cancer cell toxicity, genotoxicity as well as S phase cell cycle arrest and apoptosis via the intrinsic and extrinsic pathways. The anticancer activity of the MeOH leaf extract of M. balsamina as well as its antioxidant potential may be attributed to the presence and relative abundance of flavonol glycosides, cucurbitane-type triterpenoid aglycones, and cucurbitane-type glycosides. Although the MeOH extract may potentially reverse the effects of P-gp multidrug resistance by decreasing its activity, its inhibition of the activity of CYPs 1A2, 2A6, 2C8 and, 2C9, which are involved in the metabolism of more than 80% of the drugs in clinical use may suggest that co-administration of the MeOH extract may still result in increased plasma levels of drugs, thereby resulting in toxicity. The H2O extract, although not pro-apoptotic as the MeOH extract may still have the potential to be developed as a nutraceutical as it was shown to exhibit no adverse drug interactions and because this species is known to possess a wide variety of nutritional and medicinal values. / South African Medical Research Council (SAMRC) Research Capacity Development Initiative.

Indiana University-Purdue University Indianapolis (IUPUI) / Men’s adherence to masculinity norms has been implicated as a risk factor for unhealthy behaviors (e.g., drinking to intoxication, having unprotected sex with multiple, simultaneous partners) and lack of engagement in healthy behaviors (e.g., blood pressure screening, cholesterol screening, wearing protective clothing while in the sun, receipt of annual medical and dental exams) (Boman & Walker, 2010; Courtenay, 2000a, 2000b, 2011; Hammond, Matthews, & Corbie-Smith, 2010; Iwamoto, Cheng, Lee, Takamatsu, & Gordon, 2011; Locke & Mahalik, 2005; Mahalik, Lagan, & Morrison, 2006; Mahalik et al., 2003; Nicholas, 2000; Pachankis, Westmaas, & Dougherty, 2011; Pleck, Sonenstein, & Ku, 1993; Wade, 2009). Masculinity has been defined as behaviors, beliefs, and personality characteristics associated more often with men than women as well as characteristics and behaviors that society prescribes and reinforces in men (Thompson, Pleck, & Ferrera, 1992). Rooted in geographical, cultural, and temporal environments, diverse masculinities have emerged throughout the United States and the world (Connell, 1995; Courtenay, 2011). Traditional masculinity beliefs and behaviors in the United States include the sturdy oak (men should be tough, self-reliant, stoic, and confident), no sissy stuff (men should avoid feminine characteristics and behaviors), the big wheel (men should strive for success and status), and give ‘em hell (men should embrace aggressiveness, daring, and violence) (Brannon, 1976). Numerous qualitative studies have suggested that some men find cancer screening examinations involving the rectum (i.e., endoscopy for colorectal cancer [CRC] screening or digital rectal examination [DRE] for prostate cancer screening) an affront to their masculinity (see Table 1 for quotations from these studies) (Bass et al., 2011; Beeker, Kraft, Southwell, & Jorgensen, 2000; Getrich et al., 2012; Goldman, Diaz, & Kim, 2009; Harvey & Alston, 2011; Holt et al., 2009; Jilcott Pitts et al., 2013; Jones, Devers, Kuzel, & Woolf, 2010; Rivera-Ramos & Buki, 2011; Thompson, Reeder, & Abel, 2011; Wackerbarth, Peters, & Haist, 2005; Winterich et al., 2009). However, to the author’s knowledge, no quantitative studies have considered the role of masculinity in CRC screening adherence. Unfortunately, current CRC screening rates fall below the 70.5% Healthy People 2020 screening objective (U.S. Department of Health and Human Services, 2012).Research is needed to better understand relationships between men’s masculinity norms and CRC screening adherence so that interventions may be developed to reduce barriers to screening, improve screening rates, and, ultimately, decrease men’s mortality from CRC. The present study will address this gap in the literature by examining the masculinity norms and CRC screening adherence of male veterans aged 51-75 years who are at average CRC risk (Levin et al., 2008). First, the prevalence of CRC, its risk factors and warning signs as well as CRC screening techniques, screening rates, and characteristics of individuals who are adherent and non-adherent to CRC screening guidelines are summarized. Next, the concept of masculinity, theoretical and empirical support for studying masculinity norms within the context of CRC screening, and potential relationships between masculinity norms and colorectal cancer screening behaviors are described. Finally, the study methods, results, and future directions and limitations of this research are described.

No description available.