This reseach firstly investigated iodine-induced apoptotic effects and the underlying mechanism in thyroid cancer cells. Results indicated that apoptosis induced by iodine, especially at high dose of iodine (100 muM), was mitochondrial-mediated, with the loss of mitochondrial membrane potential, Bak up-regulation, caspase 3 activation and cytochrome C release from mitochondria. Iodine treatment decreased the level of mutant p53 including the R273H mutant that possesses anti-apoptotic features while increased the p21 level. The block of p21 significantly prevented iodine-induced apoptosis. High doses of iodine also stimulated the transient activation of the subfamily members of MAPKs (ERK1/2, p38 and JNK1/2). The results showed the three subfamily members of MAPKs all worked as anti-apoptotic factors. Surprisingly, high doses of iodine promoted instead of suppressed the expression of anti-apoptotic protein Bcl-xL expression. The increase of Bc1-xL was likely to compensate the damage induced by iodine since the inhibition of Bc1-xL accelerated iodine-mediated apoptosis. Collectively, iodine induced mitochondrial-mediated apoptosis in thyroid cancer cells. This apoptotic pathway was involved in the activation of MAPKs pathways, which may subsequently up-regulate p21, Bc1-xL, and down-regulate anti-apoptotic mutant p53 expression. The findings provide solid molecular evidence to explain the epidemiological observation that iodine insufficiency promotes the thyroid tumor development. It may also reveal some novel molecular targets for the treatment of thyroid cancer. / Thyroid cancer is the most common endocrine malignancy and exhibits the full range of malignant behaviors from the relatively indolent occult differentiated thyroid cancer to uniformly aggressive and lethal anaplastic thyroid cancer. Iodine is a well known key element in thyroid normal function maintenance and thyroid cancer development. However, the mechanisms of iodine in thyroid cancer cells development are limited. Recent researches have indicated that iodine could induce cancer cells apoptosis, staying clear from the dysfunction of iodide-specific transportation systems in thyroid cancer cells. Thus, iodine-induced apoptosis may be an effective pathway for iodine to affect thyroid cancer development, but we know little about them. / To further explore iodine on the apoptotic effects of chemotherapeutic agents in thyroid cancer, anaplastic thyroid cancer cell line ARO was used. Anaplastic thyroid cancer is lethal because of its rapid progression and poor response to chemotherapy and radioiodine therapy. The study examined the effect of moderate dose of iodine (50 muM) on the apoptosis of ARO cells treated with doxorubicin (Dox) and histone deacetylase inhibitor sodium butyrate (NaB). The cytotoxic effect of either Dox or NaB alone was limited, but co-administration of NaB and Dox (NaB-Dox) significantly increased mitochondrial-mediated apoptosis. The effects of iodine to apoptosis-induced by the two agents were diversified. Iodine reduced the apoptosis induced by Dox or NaB-Dox but promoted apoptosis induced by NaB. To explain this diversifying finding, the experiment found that iodine exaggerated NaB-mediated Bcl-xL down-regulation. In contrast, it reduced the effect of Dox on the decrease of Bcl-xL expression. Further experiments showed that iodine regulated the level of Bcl-xL in ERK- or/and p38-related pathways. The balance between ERK and p38 may determine the iodine-modulated Bcl-xL expression. The high ERK/p38 activity ratio up-regulated Bc1-xL and enabled the tumor cells to resist chemotherapy, whereas the low ERK/p38 down-regulated Bc1-xL and sensitized the tumor cells to chemotherapy. Taken together, iodine plays a critical role in apoptosis of thyroid cancer cells induced by chemotherapeutic agents. The balance between ERK and p38 may determine cell survival and death through modulating Bcl-xL expression in thyroid cancer cells. The findings provide some new insights into the roles of iodine in chemotherapeutic agents-induced apoptosis in thyroid cancer cells. / To summarize, iodine-induced apoptotic effects on thyroid cancer cells is a key pathway for iodine to influence thyroid cancer development and chemotherapy. Meanwhile MAPKs-related mutant p53, p21 and Bcl-xL expression are critical in deciding thyroid cancer cells survival and death. Moreover, iodine can influence chemotherapeutic agents-induced apoptosis through ERK/p38-mediated Bcl-xL expression. / Liu, Xiaohong. / "December 2009." / Adviser: Charles Andrew van Hasselt. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 111-146). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Call number: LD2668 .T4 1979 L48 / Master of Science

Thesis (M.Tech.)(Nuclear Medicine) -- Central University of Technology, free State, 2007 / In the South African Health Services (SAHS) it is each health worker’s responsibility to find ways to reduce health care cost and improve health service to the public. The measurement of radioactive iodine uptake (RAIU) by the thyroid gland for diagnostic purposes has been used as early as the 1940s. The 24-hour (hr) iodine-131 (131I) uptake measurement is traditionally used for the calculation of the 131I administered activity for therapy dosage. This entails that the patient’s hospitalisation is prolonged, which increases the costs. The literature also indicates that the 24-hr 131I uptake value can be discarded and only the 6-hr 131I uptake measurement is needed to calculate administered activity for therapeutic dosages for Graves’ patients. Therefore, if it can be confirmed that the 6-hr 131I uptake measurement alone is needed, the SAHS could decrease hospitalisation costs. The overall goal of the investigation was to analyse the 6-hr and 24-hr 131I uptake measurements of patients with Graves’ disease at the Universitas Hospital. The aim was to determine the relationship between the 6-hr and 24- hr RAIU values to establish the therapeutic dosage for Graves’ disease. To achieve the aim, three objectives were set. First, to serve as a background to the investigation, a literature survey relating to the RAIU measurements of patients with Graves’ disease was made. Second, a retrospective analysis was performed by collecting the 6-hr and 24-hr 131I uptake measurements of patients with proven Graves’ disease at the Universitas Nuclear Medicine Department (UNMD). Finally, the data obtained from the retrospective analysis was analysed, summarised and compared to answer the investigation questions. The investigation group included patients with confirmed Graves’ disease who had undergone both the 6- and 24-hr 131I RAIU at the Universitas Hospital from the beginning of 2004 to the end of 2005. Graves’ disease is confirmed by the following factors at the UNMD, namely: Suppressed TSH, elevated T4 and T3 values, an increased uptake on the 99mTc-pertechnetate scan and increased 6- and 24-hr 131I RAIU values. The UNMD statistics show that 178 patients were diagnosed with Graves’ disease during this period. The patients of the investigation group included both male and female patients from different races, ranging from 15-75 years. In order to increase the validity of the investigation, all factors that could influence the accuracy of the 131I thyroid uptake test were excluded. After the exclusion and inclusion criteria had been applied, the final investigation group was made up of 124 Graves’ disease patients. The data obtained from the patient files was noted on the different data sheets (see Appendix A) for further analysis. The information from these data sheets was then used to obtain the investigation results. The Department of Biostatistics of the University of the Free State (UFS) was consulted for recommendations regarding the management of data and the processing of results. All values were summarised by means and Standard Deviations (SD) or percentiles. Mean or median differences were calculated with a 95% Confidence Interval (CI). A regression analysis was made between the 6-hr and 24-hr 131I RAIU values. The highest RAIU value is the best to calculate the therapeutic dosage, as this gives a true reflection of the thyroid function of a Graves’ disease patient. In the investigation group the median of the 24-hr 131I RAIU values was higher than the 6-hr 131I RAIU values. The findings showed that the 24-hr 131I RAIU in most of the investigation group was the highest value and most effective to calculate the 131I therapeutic dosage. At a time when research-based practice is taking on an increasingly important role, it is essential for nuclear medicine departments to make evidence-based recommendations. This investigation found that the correlation between the 6-hr and 24-hr RAIU clearly justified the cost spent on Graves’ disease patients who must stay overnight for the 24-hr 131I RAIU procedure.