Patients with trisomy of chromosome 21, known as Down’s syndrome (DS), have a lower incidence of solid tumours than unaffected age-matched individuals. However, the cellular and molecular basis for this observation is not well understood. We hypothesised that a direct link between Down’s syndrome and angiogenesis exists, whereby the overexpression of human chromosome 21 (Hsa21) genes causes the repression of angiogenesis (gene dosage effects) resulting in the inhibition of solid tumour growth. In this project we investigated the angiogenic phenotype of an animal model of Down’s syndrome, the Tc1 mouse, which contains a large freely segregating fragment of Hsa21 containing over 200 human genes. We found that the growth of both B16F0 melanoma and Lewis Lung Carcinoma cells was impaired in Tc1 mice. Tumour vascularity also was reduced. This is supportive of the epidemiological data from the human DS population and supports the hypothesis that Hsa21 contains anti-angiogenic genes. Candidate genes were selected due to their endothelial specificity or likelihood to function in angiogenesis based on functional data or similarity to other proteins. Ex vivo RNAi assays were used to examine their roles in angiogenesis. We have found that reducing the expression of human Adamts1, Erg, Jamb or Pttg1ip in Tc1 tissue can restore its angiogenic potential, suggesting that the dosage of these genes (i.e. 3 copies instead of 2) can inhibit angiogenesis. Following from this study we also examined the role of selected adhesion related genes found on chromosome 21 in angiogenesis. Cldn14 encodes the tight junction molecule Claudin14 but its role in angiogenesis was unknown. We found that partial, but not complete, depletion of Cldn14 can increase the proportion of non-lumenated tumour blood vessels; decrease supporting cell association with tumour vessels; and increase endothelial cell proliferation in vivo, ex vivo and in vitro. Taken together this series of experiments has identified novel regulators of angiogenesis and has demonstrated the gene dosage effects of a subset of Hsa21 genes on angiogenic processes.

研究目的：結腸癌是現今最常見的惡性腫瘤之一。在西方國家， 其發病率甚至居惡性腫瘤的第二位，在我國發病率居第四位，並且發病率在不斷攀升。在長江中下游，江淅地區，福建，香港等較為發達地區發病率較高，研究提示可能與經濟發達、生活習慣以及飲食習慣有密切關係。隨著醫療技術的進步，西醫針對結腸癌已有多種治療手段。其中，于術治療、放化療綜合治療是主要的治療手段。但在一定程度上對患者機體有一定的毒副作用，嚴重影響生活品質，並且復發和轉移率較高。研究者發現一些中藥對結腸癌細胞有抑制細胞生長、影響腫瘤細胞相關資訊表達、抑制腫瘤細胞血管生成、誘導腫瘤細胞凋亡、對信號轉導通路的影響等作用。中草藥毒副作用小，成本低廉，提高患者生活品質，降低復發和轉移率。因此，中藥對結腸癌的抑制作用有較高的研究價值。 研究方法：選取人結腸癌HCTl 16 細胞用McCoys 5A 的細胞培養液放置於37 ℃、C02 體積分數為5%的培養箱中靜置培養。研究藥物選擇首先對結腸癌進行中醫辨證，分析每種證型用藥特點。其次在中國期刊全文資料庫進行關於結腸癌文獻檢索，在檢索結果中找出辨證分析中藥物出現頻率較高的。最後，查找相關碩士、博士論文以及有關結腸癌書籍資料篩選出以下幾種進行考證對結腸癌細胞是否有抑制作用的中草藥。（土茯苓、白花蛇古草、馬齒莧、藤梨根、敗醬草、白頭翁） 。分別用DCM 以及MEOH 提取土茯苓、白花蛇古草、馬齒莧、藤梨根、敗醬草、白頭翁，將培養好的細胞種植在96 孔板上，分別加入上述藥物提取物。用SRB 法檢測細胞的增殖情況。 研究結果： 根據實驗所得數據發現， 其中茯夜苓、和敗醬草的DCM 提取液均對HCT116細胞有較強的抑制作用，白花蛇古草對此種結腸癌細胞雖有抑制細胞增殖的作用，但結果並不明顯，實驗所得結果還有待反復實驗，以及進一步探究作用機制。然而藤梨根、馬齒莧、白頭翁的DCM 提取液以及用MEOH 提取的上述藥物均對細胞HCT116 無明顯抑制作用， 考慮實驗僅對單一細胞進行，檢測藥物提取物作用於HCT116 細胞的抑制性 。因此， 本實驗僅為六種中草藥提純物對HCT l 16 細胞的抑制作用初步探究，還有待進一步深入研究。

Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Psychology." Includes bibliographical references (p. 70-74).

No description available.

Thesis (M. Pharm. (Pharmacy Practice)--North-West University, Potchefstroom Campus, 2009.

Cancer is a broad term used to describe more than 100 diseases that can affect any part of the body. Cancer is the uncontrollable division of abnormal cells in the human body, which can invade nearby tissue and spread through the bloodstream to other parts of the body (National Cancer Institute, 2007b). Cancer can affect people all over the world, from every race, society and age (Albrecht, 2006:3). The treatment of cancer is becoming more and more expensive as newer and more effective drugs enter the market (Niezen et al., 2006:2887) and diagnosing and screening of cancer patients is showing remarkable progress (Meropol & Schulman, 2007:180). The general objective of this study was to investigate and review the prescribing patterns of antineoplastic and immunomodulating agents in a section of the private health care sector of South Africa. This research can be classified as retrospective and quantitative. Data were obtained from a medicine claims database, of a pharmacy benefit management company. The study population consisted of all prescriptions, containing one or more cancer medicine items (classified according to the ATC classification), for the study period January 2005 to December 2006. Different aspects of cancer were investigated in order to determine the international and national prevalence of cancer and types of cancer and cancer treatment. An overview of managed care aspects were given and through this study it is evident that pharmacoeconomic studies and other managed care aspects could play a major role as information system in the decision making about cancer treatments. The prescribing patterns of antineoplastic and immunomodulating agents were reviewed, analysed and interpreted. It was determined that the number of cancer patients, the number of prescriptions containing one of more cancer drug and the number of cancer medicine items respectively comprised less than 1% of the total number of patients, prescriptions and medicine items recorded on the total database. To the contrary, the total cost of cancer medicine items comprised 4.00% and 5.31% of the total cost of all medicine items (total database) in 2005 and 2006 respectively. This indicates the relatively high cost of cancer medicine items. Almost 50% of all cancer patients are 59 years of age or older and the total cost of cancer medicine items claimed by patients 59 years and older comprised almost 60% of the total cost of all cancer medicine items claimed during the two study years respectively. Cancer medicine items claimed by patients <19 years of age comprised only 2% of all cancer medicine items claimed in both study years and less than 1% of the total cost of all cancer medicine items. Cancer medicine items claimed by patients between the age of 19 and 59 years of age comprised 45.32% and 44.80% of the total number of cancer medicine items in 2005 and 2006 respectively whilst the cost for these age groups comprised 40.81% and 40.73% of the total cost of cancer medicine items. More than 70% of all cancer patients in 2005 and 2006 were females whilst male cancer patients comprised about 30% of all cancer patients. The number of cancer medicine items claimed by female cancer patients also comprised more than 70% of the total number of cancer medicine items claimed in 2005 and 2006, however, the total cost of cancer medicine items was divided almost even between male (45%) and female (55%) cancer patients for both study years. Therefore, according to this study, cancer medicine items claimed by male cancer patients are relatively more expensive than those claimed by female cancer patients. In completion of this study, recommendations for further studies concerning cancer treatment and cost-effective usage of cancer medicine were formulated, including the influence of the nature of the cancer, the age and gender of the patients as well as the treatment costs of cancer. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Cancer is a broad term used to describe more than 100 diseases that can affect any part of the body. Cancer is the uncontrollable division of abnormal cells in the human body, which can invade nearby tissue and spread through the bloodstream to other parts of the body (National Cancer Institute, 2007b). Cancer can affect people all over the world, from every race, society and age (Albrecht, 2006:3). The treatment of cancer is becoming more and more expensive as newer and more effective drugs enter the market (Niezen et al., 2006:2887) and diagnosing and screening of cancer patients is showing remarkable progress (Meropol & Schulman, 2007:180). The general objective of this study was to investigate and review the prescribing patterns of antineoplastic and immunomodulating agents in a section of the private health care sector of South Africa. This research can be classified as retrospective and quantitative. Data were obtained from a medicine claims database, of a pharmacy benefit management company. The study population consisted of all prescriptions, containing one or more cancer medicine items (classified according to the ATC classification), for the study period January 2005 to December 2006. Different aspects of cancer were investigated in order to determine the international and national prevalence of cancer and types of cancer and cancer treatment. An overview of managed care aspects were given and through this study it is evident that pharmacoeconomic studies and other managed care aspects could play a major role as information system in the decision making about cancer treatments. The prescribing patterns of antineoplastic and immunomodulating agents were reviewed, analysed and interpreted. It was determined that the number of cancer patients, the number of prescriptions containing one of more cancer drug and the number of cancer medicine items respectively comprised less than 1% of the total number of patients, prescriptions and medicine items recorded on the total database. To the contrary, the total cost of cancer medicine items comprised 4.00% and 5.31% of the total cost of all medicine items (total database) in 2005 and 2006 respectively. This indicates the relatively high cost of cancer medicine items. Almost 50% of all cancer patients are 59 years of age or older and the total cost of cancer medicine items claimed by patients 59 years and older comprised almost 60% of the total cost of all cancer medicine items claimed during the two study years respectively. Cancer medicine items claimed by patients <19 years of age comprised only 2% of all cancer medicine items claimed in both study years and less than 1% of the total cost of all cancer medicine items. Cancer medicine items claimed by patients between the age of 19 and 59 years of age comprised 45.32% and 44.80% of the total number of cancer medicine items in 2005 and 2006 respectively whilst the cost for these age groups comprised 40.81% and 40.73% of the total cost of cancer medicine items. More than 70% of all cancer patients in 2005 and 2006 were females whilst male cancer patients comprised about 30% of all cancer patients. The number of cancer medicine items claimed by female cancer patients also comprised more than 70% of the total number of cancer medicine items claimed in 2005 and 2006, however, the total cost of cancer medicine items was divided almost even between male (45%) and female (55%) cancer patients for both study years. Therefore, according to this study, cancer medicine items claimed by male cancer patients are relatively more expensive than those claimed by female cancer patients. In completion of this study, recommendations for further studies concerning cancer treatment and cost-effective usage of cancer medicine were formulated, including the influence of the nature of the cancer, the age and gender of the patients as well as the treatment costs of cancer. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2009.

Includes bibliographical references and index.