BACKGROUND: Colorectal cancer is usually asymptomatic until later stage and the 5-year survival for stage III or IV are 68% and 10 % because of delayed diagnosis. Worldwide, it is the 4th leading cause of death among cancers which accounted for 694,000 deaths in 2012. While healthy diet and lifestyle helps prevent colorectal cancer, increased surveillance through screening has been suggested to attribute to the decreasing trend of colorectal cancer incidence in the United States in the past decade. Identifying what type of colorectal cancer screening methods is more effective is of public health relevance to Hong Kong where colorectal cancer ranks the top leading cancer. OBJECTIVES: To conduct a systematically review on current literatures to examine whether endoscopy screening by flexible sigmoidoscopy or colonoscopy is more effective for reducing the mortality and incidence of colorectal cancer than no screening as many colorectal cancers arise from adenomatous polyps, which polypectomy is hypothesized to be protective. Meanwhile, different countries adopt different kinds of colorectal cancer screening modalities, but yet, there is no agreement for the types of screening. METHODS: Four databases, Medline (OVIDSP), Pubmed, CINAHL plus (EBSCOhost), Embase (OVIDSP) were used to search for published journals. Reference list of the identified articles were screened for more relevant studies. RESULTS: A total of 8 studies were included in this systematic review. There were only 2 randomized controlled trials (RCTs) on screening for colorectal cancer using flexible sigmoidoscopy in asymptomatic and average-risk people and no RCT was found for colonoscopy. Based on the studies reviewed, findings were inconsistent on whether endoscopy screening is more effective in reducing overall colorectal cancer incidence and mortality than no screening. Endoscopy screening, either sigmoidoscopy or colonoscopy was associated with lower incidence of distal colorectal cancer. CONCLUSION: Screening by flexible sigmoidoscopy or colonoscopy is not clearly associated with lower overall colorectal cancer risks based on current systematic review. Randomized controlled trials or retrospective cohorts are required to clarify the effectiveness of endoscopy screening before considering the implementation of population-wide colorectal cancer screening. / published_or_final_version / Public Health / Master / Master of Public Health

Colorectal cancer is a serious health problem that has concerned people for decades. In Hong Kong, it is the most common cancer and the second leading cause of death. Among colorectal cancer patients, around 40-50% of them will develop metastatic disease. Chemotherapy is playing an important role all the time in the treatment of advanced colorectal cancer. In the past decade, the application of targeted therapies in treatment has largely improved efficacy and prolonged survival. Bevacizumab and cetuximab are two commonly used targeted agents in daily clinical practice of Hong Kong. Since multiple clinical trials have studied bevacizumab and cetuximab in combination with other chemotherapies, limited data is available in Asian patients. Therefore, we conduct three 5-year retrospective analyses based on patients received treatment in Hong Kong Queen Mary Hospital, to investigate the clinical efficacy and toxicity of those two drugs. The first study examined the use of bevacizumab in treating KRAS mutated type patients. We found the efficacy and results were consistent with historical data. In the next analysis of cetuximab, comparable data were shown which suggested the consistency with previous studies. The last study is aim to compare bevacizumab and cetuximab in previously untreated wild-type KRAS patients. Identical response rates, progression-free survival and overall survival were finally reported. / published_or_final_version / Medicine / Master / Master of Philosophy

Colorectal cancer is the third most common cancer and cause of death due to cancer in the United States. Death due to colorectal cancer is generally caused by hepatic metastasis rather than the primary tumor itself. The five-year survival rate is only 10% for patients whose colorectal cancer metastasized, which indicates the need for more effective therapies to treat colon cancer. The diet contains (1) preformed vitamin A as retinyl esters in animal-derived food sources and (2) provitamin A carotenoids in plant-derived food sources. Once absorbed, retinol is re-esterified and transported to the liver, the major site of vitamin A storage. Therefore, dietary vitamin A supplementation can increase retinol levels in the colon and liver, potentially affecting both primary colon tumors and liver metastases of the primary tumors. All-trans--retinoic acid (ATRA) is thought to regulate most of the effects of retinoids, via the ATRA/RAR/RARE pathway exerting an inhibitory effect on cancer growth and progression. As cancer progresses, colon cancer acquires the resistance to ATRA. The purpose of this study is to understand the mechanism by which retinol decreased the growth and progression of ATRA-resistant human colon cancer in vivo and in vitro. We first demonstrated that retinol decreased the growth of ATRA-resistant colon cancer cells by arresting cell cycle progression independent of the ATRA/RAR/RARE pathway. Next, we showed retinol inhibited ATRA-resistant human colon cancer cell invasion by decreasing MMP-2, -9 and PI3K activity in vitro. Finally, dietary vitamin A supplementation decreased the incidence and multiplicity of liver metastases in nude mice intrasplenically injected with ATRA-resistant human colon cancer cells. Taken together, these data suggest the possibility of dietary vitamin A supplementation for colon cancer therapy and prevention.

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

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No description available.

En los seres humanos, los tumores del intestino grueso constituyen una causa importante de morvilidad y mortalidad en gran parte del mundo. Factores dietéticos y del medio ambiente son considerados como responsables del 85-90 de todos los casos. En humanos y en animales de laboratorios fue evaluada la relación entre el cáncer de colon y componentes de la dieta tales como grasas, fibras, vegetales, vitaminas y diversos elementos como, calcio, magnesio, hierro, potacio, sodio, manganeso, zinc, cobre, fósforo, y selenio. Con referencia al molibdeno (Mo), varios estudios han demostrado el efecto protector sobre la carcinogénesis experimental en diferentes modelos biológicos. El objetivo del presente trabajo fue investigar el efecto de la molibdenosis y la deficiencia del Mo sobre la carcinogénesis experimental del colon en ratas. Fueron utilizadas ratas Wistar machos, de 3 meses de edad a las cuales se les suministro agua y dieta ad-libitum. El Mo y el Tungsteno (W) fueron administrados en el agua de bebida a la concentración de 200 ppm. Los tumores intestinales fueron inducidos mediante una inyección subcutanea semanal del carcinógeno 1, 2- dimetilhidrazina (DMH) durante 16 semanas, a la dosis de 20 mg/kg de peso corporal. El Mo, en la forma molibdato de amonio [(NH4)6 Mo7O24 4H2O] y el W, en la forma de tungstenato de sodio (Na2WO4) fueron administrados en el agua de bebida 2 meses antes del primer tratamiento con DMH y continuado durante 4 meses más hasta la última dosis de la DMH. Todos los animales fueron sacrificados tres meses posteriores a la última dosis de la DMH. El examen macroscópico consistió en la determinación de las características, tamaño y localización de los tumores. Los cambios del epitelio intestinal y del contenido de mucinas fueron estudiados histológica e histoquímicamente en preparados cortados en 5 um y coloreados con hematoxilina y eocina, PAS y Alcian blue a pH 2,5. Los tumores y las lesiones neoplásicas tempranas (LNT) fueron analizadas mediante microscopía electrónica de barrido. En los lotes tratados con Mo y en los lotes tratados con W se observo un incremento y una disminución del contenido hepático de Mo, respectivamente. Al final del primer mes de tratamiento, en lote tratado con Mo, el contenido hepático de Mo fue de 4,65 ppm y al segundo mes fue de 5,61 ppm, comparado con el lote sin tratamiento 2,61 ppm y 2,18 ppm, mientras que en lote tratado con W fue de 0,70 ppm y 0,96 ppm respectivamente. Se observo una incidencia significativamente menor de tumores en el lote tratado con Mo (47 tumores), comparado con el lote tratado con DMH (105) y el lote tratado con W (113). Por otra parte el lote tratado con molibdeno mostro una disminución significativa en el número de tumores múltiples por rata. / In human beings, large intestine tumors constitute an important cause of morbidity and mortality in most of the countries of the world. Environmenatl and dietary factors are considered to be responsible for 85-90 of all the cases. In humans and laboratory animals it was evaluated the relationship between colon cancer and dietary components such as fat, fibers, vegetables, vitamins and some elements such as magnesium, iron, potassium, sodium, manganese, zinc, copper, phosphorous and selenium. Referring to molybdenum (Mo), several studies have demonstred its protective effect in different experimental carcinogenesis models. The main objective of the present study was to investigate the effect of molybdenosis and molybdenum deficiency on experimental colon carcinogenesis in rats. Three months old male Wistar rats, were given ad-libitum a nutritionally adequate diet and demineralized drinking water. The Mo and Tungsten (W) were provided in the drinking water at 200 ppm concentration. Intestinal tumors were induced by 1,2-dimethylhydrazine (DMH) given subcutaneosly at 20 mg/kg body weight and continued once a week for 16 weeks. Mo in the form of ammonium molybdate [(NH4)6 MO7O24 4H2O] and W in the form of sodium tungstate (Na2WO4) were provided in the drinking water to months before the first DMH treatment and it was continued during 4 months more until the last DMH treatment. Three months after the last carcinogen injection, all survinving animals were sacrificed and examined for intestinal tumors. The features, size and location of the tumors were recorded and they were examined and clasificated histologically. Histological and histochemical changes of intestinal epithelium and mucins were assessed at the end of the experience in specimens sectioned at 5 um, stained with Hematoxylin and Eosin, PAS and Alician blue pH 2,5. Scanning electron microscopy of tumors and early neoplas lesions (LNT) were examined. High Mo intake did not cause any general DMH toxicity as assessed bay body weight gain. The groups treated with Mo and the groups treated with W showed an increase and decrease of hepatic content of Mo was 4,65 ppm in the group treated with W 0,70 ppm and 0,96 ppm respectively. A significantly lower incidence of tumors was observed in the Mo group (47), compared with the control group given DMH alone (105) and the group treated with W (113). On the other hand, the group treated with Mo showed a significant decrease in the number of multiple tumors per rat.

Consumption of whole grains has been linked to reduced risk of colon cancer. This study determined estrogenic activity of sorghum phenolic extracts of different phenolic profiles and identified possible estrogenic compounds in sorghum in vitro, as well as evaluated the potential of estrogenic sorghum phenolic extracts to prevent colon carcinogenesis in vivo. The thermal stability of sorghum 3-deoxyanthocyanins was also studied, to determine their suitability as functional food colorants. White and TX430 (black) sorghum extracts showed estrogenic activity in cell models predominantly expressing estrogen receptor-α (ERα) or ERβ at 5 and 10 µg/mL, respectively. The same treatments led to induction of apoptosis in cells expressing ERβ. The red TX2911 sorghum did not possess these activities. Compositional analysis revealed differences in flavones and flavanones. Flavones with estrogen-like properties, i.e. luteolin and apigenin, were detected in White and TX430 (black) sorghum extracts, but not in red TX2911 extract. Naringenin, a flavanone known to antagonize ERα signalling, was only detected in the red TX2911 extract. Additional experiments with sorghum extracts of distinct flavones/flavanone ratio, as well as with pure apigenin and naringenin, suggested that flavones are the more potent ERβ agonists in sorghum. On the other hand, 3-deoxyanthocyanins were probably not estrogenic. Estrogenic white and black sorghum phenolic extracts (fed at 1% level in the diet) reduced the number of azoxymethane induced colon premalignant lesion (aberrant crypt foci) by 39.3% and 14.7%, respectively, in ovariectomized mice. Further studies are needed to elucidate the protective mechanisms induced by these sorghum extracts. Sorghum 3-deoxyanthocyanins retained good color stability after 30 minutes of heat treatment at 121 °C under pressure: More than 80% of color retained in pH 1 and 2 HCl and citric acid solutions, and 39-84% retained from pHs 3-7. Formic acid negatively affected the color stability at pH 1 and pH 2 due to its reducing capacity. Methoxylation decreased the thermal stability of 3-deoxyanthocyanins. The heat stability of 3-deoxyanthocyanins indicates good potential for food use. Overall, the inherent estrogenic activity of specific sorghum phenolic extracts is a likely mechanism for colon cancer prevention. Further studies are needed to assess physiologically relevant dietary level of sorghum phenolics for prevention of colon cancer, and effect of food processing on the activity and bioavailability of the chemopreventive components.

Secondly, we incorporate knowledge of the physiology, or how we expect the anatomy to change due to treatment. We can represent these changes using the Jacobian of the deformation, which describes the local size and type of change. This is used to regularise the registration, and can be incorporated simultaneously with the iterations of the registration. The final result is an accurate and robust registration result that is clinically useful for finding corresponding features on pre- and post-treatment datasets.

The acute cellular responses to DNA damaging agents are critical in determining the long term outcome of disease. A cell’s susceptibility to damage, or its capacity to remove or repair this damage, all contributes to the eventual health or disease of tissues. This process is especially crucial in colonic epithelial cells and in the development of colorectal oncogenesis. The colonic lumen is constantly subjected to different environmental compounds that may have genotoxic properties that can initiate mutational events and possibly carcinogenesis. Therefore, the study of a regulatory dietary agent that improves the colonic cells ability to withstand damage, improve repair and retain its general health is a significant and practical tool in the fight against colorectal cancer. The health benefits of fish oil, including its potential chemopreventative properties, have been reported in numerous studies. However, the mechanism by which this protective effect occurs remains unclear. A gap in current literature exists that fails to explore the effect of fish oil on the early cellular responses to carcinogenic agents. Therefore, this thesis aims to firstly, better understand the specific host responses to an insult of carcinogen in vivo; secondly, to determine if regulation of these responses can be achieved by dietary fish oil; and lastly, to explore the potential consequences of this regulation for colorectal oncogenesis. All experimental work was carried out using a rat – azoxymethane (AOM) animal model of colorectal carcinogenesis. The key host responses to the carcinogen that were measured included the formation of acute O6methyldeoxyGuanosine (O6medG) DNA damage, the acute apoptotic response to genotoxic carcinogen (AARGC) and cell proliferation rates. A novel immunochemical assay was designed to detect both the levels and distribution of O6medG in colonic cells. With this established, a pattern of these host responses were mapped out over time. A dietary intervention study trialling a range of fish oil diets containing different doses and forms was then carried out to determine if modulation of responses occurred. This study was then followed on by a longer term study that explored the consequences of regulation by fish oil on pre-neoplastic lesions in the colon. The acute host responses to an insult of AOM showed that colonic O6medG formation began 2h post AOM administration and peaked at 6h. The AARGC response followed the pattern of O6medG by a 2h delay, peaking at 8h post AOM administration, while cell proliferation rates decreased significantly after 6h. The inclusion of tuna oil in the diet did not affect either the AARGC or cell proliferation rates when given in any form or at any dose. Animals fed a diet with 15% free tuna oil and 7% encapsulated tuna oil did however have significantly reduced levels of O6medG DNA damage in the distal colon. This reduction in O6medG levels did not translate into a reduction of ACF lesion, with a protective effect against ACF lesions only being observed in animals fed the high dose fish oil groups. Analysis of the data suggest that the acute host responses to an insult of DNA damaging agent appear to be closely related, all reaching their peak level of response 6-8h after the insult. The short time frame between both O6medG and apoptosis also did not support the current popular theory which explains O6medG mediated apoptosis. An alternate hypothesised BER mediated apoptotic pathway was also not supported. Regulation of the acute apoptotic response or the cell proliferation rate was not achieved by dietary fish oil. However, a high dose fish oil diet did regulate the level of O6medG in colonic epithelial cells by significantly reducing the total O6medG DNA damage load. This reduction of O6medG by a high fish oil diet however, was not translated into a protective effect against the formation of pre-neoplastic lesions. These data suggests that regulation of the acute O6medG response to a damaging agent does not necessarily imply protection for longer term colorectal oncogenesis. Additional studies exploring both the effect of fish oil on AOM metabolising enzymes and also a longer term cancer study may help to answer some pertinent questions evolving from this thesis.