Hoi, Wan Heng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 212-245). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

目的： 尽管过去几十年癌症的化疗取得了很大进步，但晚期非小细胞肺癌的预后仍然较差。表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors，EGFR TKIs）给晚期非小细胞肺癌的患者带来了新的希望。然而，EGFR TKIs的总体效果有限，且不良反应较多，价格也较昂贵。如果能找到EGFR TKIs的疗效预测因子，则该治疗就可以只给予那些最有可能从中获益的人，从而提高成本效果，并使治疗变得更加个体化。 / 已有单组研究在接受EGFR TKIs治疗的患者中对有或没有某个标志物的人的预后进行了比较，发现EGFR基因突变、EGFR基因拷贝数增加、EGFR蛋白表达和KRAS基因突变这4个生物标志物可能能够预测EGFR TKIs的疗效。然而，此类研究的方法学是有缺陷的。要确定以上生物标志物是否有预测作用，应该在评估EGFR TKIs疗效的随机对照试验中作亚组分析，对该治疗在有某个生物标志物及没有某个生物标志物的患者中的疗效进行比较，检测治疗与生物标记物的交互作用。 / 但是，现有的随机对照试验通常样本量较小，统计效能不足，难以从中得到确定的结论。因此，我们做了一个随机对照试验的系统综述，以总结现有的最佳证据，对EGFR TKIs与上述4个生物标志物的交互作用进行评估。 / 方法： 我们检索了PubMed，EMBASE，考科蓝图书馆，中国生物医学文献数据库（中文），万方数据库（中文），美国临床肿瘤学会和欧洲肿瘤学会的会议摘要，以及相关原始研究、系统综述与Meta分析、临床指南、共识及专家意见的参考文献。检索时间截至2012年6月。合格研究为非重复、提供了具体数据且符合下列所有条件的研究：1）研究对象：晚期非小细胞肺癌患者；2）干预措施：EGFR TKIs单药治疗或联合其他药物治疗；3）对照措施：安慰剂对照，空白对照或化疗，或者它们任一种加上干预组的基线治疗；4）结局指标：无进展生存期和/或总生存期；5）研究设计：随机对照试验；6）根据上述任一种或多种生物标志物的状态作了亚组分析。 / 两名研究者平行独立地从合格研究中提取了患者特征、治疗方案、结局、生物标志物分析和方法学质量等方面的资料。对每一个研究，我们都根据生物标志物阳性亚组的风险比（hazard ratio）和阴性亚组的风险比计算了一个风险比之比（ratio of hazard ratios）来测量该标志物对疗效的预测能力或者说治疗与该生物标志物的交互作用。然后，采用随机效应模型对来自不同研究的风险比之比进行Meta分析；采用Cochran Q检验和I²评估研究间的异质性；通过敏感性分析考察原始研究的方法学质量等因素对结果的影响；采用Begg漏斗图和Egger检验来检测发表偏倚存在的可能性。 / 结果： 共有18个合格研究入选。可用于各个生物标志物分析的患者数量从1763到3246不等。原始研究普遍对关于方法学质量的信息报告得不够充分；有的研究可能存在重要偏倚。与安慰剂相比，EGFR TKIs可以有效延长无进展生存期和总生存期，但对总生存期的效果相对较小。除了在EGFR基因突变的患者中EGFR TKIs延长无进展生存期的效果明显好于化疗外，其它情形下，不管是无进展生存期还是总生存期，EGFR TKIs与化疗的效果均相当。 / 以无进展生存期为结局的风险比之比，在EGFR基因突变状态不同的亚组间（野生型亚组为参照）为0.37（95% 置信区间[CI]：0.22-0.60，P < 0.0001），EGFR基因拷贝数状态不同的亚组间（未增加的亚组为参照）为0.72（95% CI：0.52-0.99，P = 0.04），EGFR蛋白表达状态不同的亚组间（无表达的亚组为参照）为0.99（95% CI：0.78-1.26，P = 0.93），KRAS基因突变状态不同的亚组间（野生型亚组为参照）为1.35（95% CI：1.02-1.80，P = 0.04）。这些结果提示EGFR TKIs治疗与EGFR基因突变，EGFR基因拷贝数及KRAS基因突变之间可能存在交互作用。以总生存期为结局的风险比之比，在EGFR基因突变、EGFR基因拷贝数、EGFR蛋白表达及KRAS基因突变状态不同的亚组间分别为0.84（95% CI：0.64-1.11，P = 0.22）、0.92（95% CI：0.69-1.23，P = 0.57）、0.86（95% CI：0.70-1.05，P = 0.14）和1.37（95% CI：0.89-2.10，P = 0.15）。 / 就统计学显著性、异质性和稳定性而言，关于其它3个生物标志物的结果不如EGFR基因突变的相关结果确定，关于总生存期的结果不如无进展生存期的相关结果确定。没有证据表明本研究中存在发表偏倚。 / 结论： EGFR基因突变可用于确定哪些患者更有可能从EGFR TKIs治疗中获益。EGFR基因拷贝数增加和KRAS基因突变可能也有类似用途，但它们与治疗的交互作用是独立存在的还是由于它们与EGFR基因突变的相关性而获得的，目前尚不清楚。在EGFR野生型的患者中，选择化疗似乎比EGFR TKIs更好，因为它的副作用相对较少，且更为便宜。 / 本研究的结果为当前的临床指南提供了全面的证据支持。其它3个标志物在EGFR野生型患者中的预测价值可能还值得进一步的探讨，但我们更建议未来的研究在探讨治疗与生物标志物的交互作用时进行多因素分析。 / Objective: Despite the many new progresses in chemotherapy, the prognosis of advanced non-small cell lung cancer (NSCLC) remains poor. The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) seems to offer new promises for advanced NSCLC patients. However, EGFR TKIs have a limited overall efficacy, clear adverse events and large costs. It has become particularly appealing to identify, through new biomarkers, patients who are more likely to benefit from the treatment so that the treatment can be more personalized and effective. / EGFR mutations, EGFR gene copy number gain, EGFR protein expression and KRAS mutations were indicated as potential predictive biomarkers for the efficacy of the treatment in single-arm studies that compared survival of treated patients with and without a biomarker. However, such comparisons are flawed and the appropriate study design to evaluate the value of a biomarker in predicting efficacy which is known as interaction in epidemiology is the randomized controlled trial with stratified analysis that compared the efficacy of EGFR TKIs between patients with and without the biomarker. / As trials in this field are usually small in sample size and insufficiently powered for drawing a robust conclusion, we conducted this systematic review to summarize the evidence from all relevant randomized controlled trials that have data for investigating the interaction between EGFR TKIs and the 4 biomarkers. / Methods: PubMed, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (in Chinese), Wanfang Data (in Chinese), the abstracts of conferences of the American Society of Clinical Oncology and European Society of Medical Oncology, the reference list of relevant original studies, systematic reviews and meta-analyses, guidelines, consensus, and expert opinions were searched up to June 2012. / Eligible studies had to be non-duplicate, extractable studies meeting all the following criteria: 1) Population: patients with advanced NSCLC; 2) Intervention: EGFR TKIs alone or EGFR TKIs plus other treatments; 3) Control: placebo, no treatment, or chemotherapy, with or without the baseline treatments in the intervention arm; 4) Outcome: progression-free survival and/or overall survival; 5) Study design: randomized controlled trial; 6) Subgroup analyses were conducted according to the status of one or more of the 4 biomarkers. / Data on patients’ characteristics, treatment protocols, outcomes, biomarker analysis and methodological quality were extracted by two researchers independently. Within a study, we defined the measure of the value of a biomarker in predicting efficacy or biomarker-treatment interaction as the hazard ratio in patients with the biomarker relative to that in those without the marker. The ratio of hazard ratios from relevant studies was then combined by using the random-effect model. / Heterogeneity among studies was assessed by the Cochran’ Q test and I². Sensitivity analyses were conducted to examine the impact of factors such as methodological quality on the results. Begg’s funnel plots and Egger’s tests were used to examine the possibility of publication bias. / Results: Eighteen studies were included. The number of patients available for analyses on different biomarkers varied from 1,763 to 3,246. Data on the methodological quality of included studies are generally under-reported. Some studies seemed to have important biases. EGFR TKIs are in general effective in increasing progression-free and overall survival as compared with placebo although the effect size is smaller for overall survival than for progression free survival. EGFR TKIs are comparable to chemotherapy in their effect in prolonging both progression-free and overall survival, except in EGFR mutation group in which EGFR TKIs seem much more effective than chemotherapy in prolonging progression-free survival. / Importantly, for progression-free survival, the summary ratio of hazard ratios was 0.37 (95% confidence interval [CI]: 0.22-0.60, P < 0.0001) for EGFR mutations (versus wild-type), 0.72 (95% CI: 0.52-0.99, P = 0.04) for EGFR gene copy number gain (versus no gain), 0.99 (95% CI: 0.78-1.26, P = 0.93) for EGFR protein expression (versus negative), and 1.35 (95% CI: 1.02-1.80, P = 0.04) for KRAS mutations (versus wild-type), indicating interaction may exist between EGFR TKIs and EGFR mutation, EGFR gene copy number and KRAS mutations. For overall survival, the summary ratio of hazard ratios for EGFR mutations, EGFR gene copy number gain, EGFR protein expression and KRAS mutations was 0.84 (95% CI: 0.64-1.11, P = 0.22), 0.92 (95% CI: 0.69-1.23, P = 0.57), 0.86 (95% CI: 0.70-1.05, P = 0.14) and 1.37 (95% CI: 0.89-2.10, P =0.15), respectively. / In general, the results on EGFR gene copy number gain, KRAS mutations and EGFR protein expression were less certain than those on EGFR mutations in terms of statistical significance, consistency and robustness, and the results on overall survival were less certain than those on progression-free survival. Publication bias did not seem present in the study. / Conclusions: EGFR mutations and possibly EGFR-GCN and KRAS mutations can help identify who are more likely to benefit from EGFR TKIs treatment. However, it is not clear whether the interaction with EGFR-GCN and KRAS mutations are independent or obtained through their relation with EGFR mutations. Furthermore, in EGFR wild-type patients, given that chemotherapy is cheaper and of fewer side effects, chemotherapy seems clearly a better choice than EGFR TKIs. / Our findings provided the most comprehensive evidence for the recommendations of current guidelines. Although the predictive value of the other 3 biomarkers in wild-type EGFR patients may be worth further investigation, we suggest that multivariate analyses are explored in future studies of biomarker-treatment interactions. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yang, Zuyao. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 88-104). / Abstracts also in Chinese. / Yang, Zuyao.

Choi, Pui Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 101-122). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.

Cheung, Tak Hong. / "July 2011." / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 166-199). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.

A 24-hour fermentation of the optimized synbiotic composed of B. longum and EPR was performed to give a cell-free fermentation broth (S24). S24 was co-cultured with two colon cancer cell lines (Caco-2 and SW620) and normal colon cells (FHC). S24 significantly inhibited cell proliferation for both colon cancer cells but promoted FHC cell growth by 10-25% as shown by MTT and BrdU arrays. Primary DNA damage analysis by alkaline comet assay showed S24 caused DNA damage to a comparable extent as the positive control of 10 mM H2O2 (treated for 1 hour) for both cancer cells. Dynamic analysis on DNA damage-associated DNA repair showed the two colon cancer cells had different response pattern to S24. Flow cytometric analysis showed that both Caco-2 and SW620 when treated with S24 (IC 50=3.66 mM of acetate) were arrested initially at G2/M and subsequently at S phase accompanied with large sub-G1 peaks. Dual staining with PI/AnnexinV further proved the appearance of apoptosis. Live cell imaging analysis on Caco-2 cells treated with S24 showed the following events: mitochondria were rapidly destroyed within the first two-hour treatment, the cells bubbled and the nucleus condensed after the mitochondrial had shrunken, followed by apoptosis. / Despite active research on synbiotic on anti-carcinogenesis of colon cancer by synbiotics, the underlying mechanism still remains unclear. This study investigated a novel synbiotic composed of non-digestible carbohydrates (NDCs) extracted from mushroom sclerotia as prebiotics and Bifidobacteria as probiotics. Preliminary results on incubation of two probiotics ( Bifidobacterium longum and Lactobacillus brevis) and one pathogenic bacterium (Clostridium celatum) separately with 3 NDCs extracted from mushroom sclerotia [Poria cocos (PC), Polyporus rhinocerus (PR) and Pleurotus tuber-regium (PT)] indicated that the growth of B. longum and L. brevis was stimulated more preferentially than C. celatum after 72-hour fermentation. The short-chain fatty acid (SCFA) profile was dominated by acetate (> 98% of total SCFAs) with very little butyrate (&lt; 2.0% of total SCFAs) and the organic matter disappearance (OMD) during fermentation was consistent with the bacterial growth. Among the synbiotic combinations, NDC from PR and B. longum gave the largest amount of acetate (2.47+/-0.232 mmol/g of organic matter disappearance). / Results obtained from human pathway finder RT2 Profiler(TM) PCR Array indicated that S24 could modulate the proliferation of colon cancer cells mainly by various pathways such as cell cycle and DNA damage repair, apoptosis and cell senescence, etc. In SW620 cells, PCR Array of Human Cell Cycle further revealed that the modulated genes mainly belonged to the gene cluster of S phase and DNA replication as well as G2 and G2/M transition. While for Caco-2 cells, the cell-cycle modulated genes mainly belonged to the cluster of G2 and G2/M transition. Immuno-blotting on the pivotal upstream regulators showed that phosphorylation of ATM at Serine 1981 was significantly increased in both cancer cells. Site-specific phosphorylation of pRB was decreased and phosphorylation of Chk1 was increased in both cancer cells while Chk2 were increased in SW620 cells. Cdc25A was phosphorylated at serine17 in both cancer cells. It can be proposed that the blockage of DNA synthesis or DNA damage was due to the down-regulation of some pivotal DNA replication related proteins such as RPA3, PCNA and MCMs, detected by ATM-Chk1/Chk2-Cdc25A pathway. This would cause the prolonged staying of cells at the G1/S checkpoint which further moved on to S phase arrest for SW620 cells. Moreover the sharply up-regulated p21, an important inhibitor of Cdk2 would further hinder the cells passing the G1/S checkpoint in SW620 cells. / The tumor suppressor p53 was detected phosphorylated at various sites in SW620 but not in Caco-2 cells. In SW620 cells, G2/M arrest was caused by the inhibition of CDK1/CDC2 due to increased expression of GADD45A and p21 and phosphorylation of Cdc25A, while for Caco-2, the G2/M arrest was caused by degradation of Cdc25A due to the absence of p53-activated GADD45A and p21 expression as shown in the pathway finder results. Some apoptosis-related proteins of Bax, Apaf-1 and PARP were modulated as shown by immuno-blotting in both colon cancer cells. (Abstract shortened by UMI.) / Gao, Shane. / Adviser: Peter Chi-Keung Cheung. / Source: Dissertation Abstracts International, Volume: 72-11, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 55-94). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Leung, Winnie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 155-164). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Figures --- p.x / Abbreviations --- p.xii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Clinical management of Cancer --- p.2 / Chapter 1.2 --- Multidrug resistance --- p.8 / Chapter 1.3 --- Aim of study --- p.14 / Chapter Chapter 2 --- Identification of gene contributing to multidrug resistance in human uterine sarcoma cells --- p.16 / Chapter 2.1 --- Introduction --- p.17 / Chapter 2.2 --- Material and Methods / Chapter 2.2.1 --- Materials / Chapter 2.2.1.1 --- Cell lines --- p.20 / Chapter 2.2.1.2 --- "Cell culture medium, supplements and buffers" --- p.20 / Chapter 2.2.1.3 --- Gene expression assay reagents --- p.22 / Chapter 2.2.1.4 --- Western blotting reagents --- p.24 / Chapter 2.2.1.5 --- MTT assay reagents --- p.29 / Chapter 2.2.1.6 --- Apoptosis analysis by flow cytometry reagents --- p.29 / Chapter 2.2.2 --- Metho --- p.ds / Chapter 2.2.2.1 --- Cell Culture --- p.31 / Chapter 2.2.2.2 --- MTT assay --- p.32 / Chapter 2.2.2.3 --- Gene expression essay (RT-PCR) --- p.33 / Chapter 2.2.2.4 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.37 / Chapter 2.2.2.5 --- Quantification of doxorubicin uptake by flow cytometry --- p.40 / Chapter 2.2.2.6 --- Apoptosis analysis by flow cytometry --- p.41 / Chapter 2.3 --- Results --- p.4 / Chapter 2.3.1 --- Cytotoxicity of doxorubicin on SA and DX5 cells --- p.43 / Chapter 2.3.2 --- mRNA expression of multidrug resistance related genes in SA and DX5 cells --- p.46 / Chapter 2.3.3 --- P-glycoprotein expression in SA and DX5 cells --- p.49 / Chapter 2.3.4 --- Doxorubicin (Dox) uptake by SA and DX5 cells --- p.51 / Chapter 2.3.5 --- Doxorubicin induced Apoptosis in SA and DX5 cells --- p.54 / Chapter 2.4 --- Discussion --- p.61 / Chapter 2.5 --- Conclusion --- p.65 / Chapter Chapter 3 --- Alternation in P-glycoprotein expression in DX5_Ninjl cells --- p.66 / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.2 --- Materials and Methods / Chapter 3.2.1 --- Materials / Chapter 3.2.1.1 --- Cell lines --- p.70 / Chapter 3.2.1.2 --- "Cell culture medium, supplements and buffers" --- p.70 / Chapter 3.2.1.3 --- Gene expression assay reagents --- p.70 / Chapter 3.2.1.4 --- Western blotting reagents --- p.72 / Chapter 3.2.1.5 --- Plasmid DNA extraction --- p.75 / Chapter 3.2.1.6 --- Transient transfection --- p.76 / Chapter 3.2.1.7 --- MTT reagents --- p.76 / Chapter 3.2.2 --- Methods / Chapter 3.2.2.1 --- Cell culture --- p.78 / Chapter 3.2.2.2 --- Gene expression essay (RT-PCR) --- p.79 / Chapter 3.2.2.3 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.81 / Chapter 3.2.2.4 --- DNA plasmid extraction --- p.83 / Chapter 3.2.2.5 --- Transient transfection --- p.84 / Chapter 3.2.2.6 --- MTT assay --- p.85 / Chapter 3.2.2.7 --- Quantification of doxorubicin (Dox) uptake by flow cytometry --- p.86 / Chapter 3.3 --- Results / Chapter 3.3.1 --- mRNA expression of Ninjurinl (Ninj1) in SA and DX5 cells --- p.87 / Chapter 3.3.2 --- The protein expression of Ninjurinl (Ninj1) in SA and DX5 cells --- p.89 / Chapter 3.3.3 --- Ninjurin1 (Ninj1) cDNA transfection in DX5 cells --- p.91 / Chapter 3.3.4 --- mRNA expression of MDR1 in Ninjurin1-transfected DX5 cells (DX5_Ninjl) --- p.93 / Chapter 3.3.5 --- P-glycoprotein expression in Ninjurin1-transfected DX5 cells --- p.95 / Chapter 3.3.6 --- "Cytotoxicity of doxorubicin (Dox) on DX5 control, DX5 vector control and DX5_Ninjl cells" --- p.97 / Chapter 3.3.7 --- "Doxorubicin (Dox) uptake by SA control, DX5 control and DX5_Ninjl cells" --- p.99 / Chapter 3.4 --- Discussion --- p.102 / Chapter 3.5 --- Conclusion --- p.105 / Chapter Chapter 4 --- Alternation in MDR1 expression in DX5一THBS1 cells --- p.106 / Chapter 4.1 --- Introduction --- p.107 / Chapter 4.2 --- Materials and Methods / Chapter 4.2.1 --- Materials / Chapter 4.2.1.1 --- Cell lines --- p.109 / Chapter 4.2.1.2 --- Cell culture medium； supplements and buffers --- p.109 / Chapter 4.2.1.3 --- Gene expression assay reagents --- p.109 / Chapter 4.2.1.4 --- Western blotting reagents --- p.111 / Chapter 4.2.1.5 --- Plasmid DNA extraction --- p.114 / Chapter 4.2.1.6 --- Transient transfection --- p.115 / Chapter 4.2.1.7 --- MTT reagents --- p.115 / Chapter 4.2.2 --- Methods / Chapter 4.2.2.1 --- Cell culture --- p.117 / Chapter 4.2.2.2 --- Gene expression essay (RT-PCR) --- p.118 / Chapter 4.2.2.3 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of protein lysate and Western blotting --- p.120 / Chapter 4.2.2.4 --- DNA plasmid extraction --- p.123 / Chapter 4.2.2.5 --- Transient transfection --- p.123 / Chapter 4.2.2.6 --- MTT assay --- p.124 / Chapter 4.2.2.7 --- Quantification of doxorubicin (Dox) uptake by flow cytometry --- p.125 / Chapter 4.3 --- Results / Chapter 4.3.1 --- mRNA expression of Thrombospondinl (THBS1) in SA and DX5 cells --- p.126 / Chapter 4.3.2 --- The protein expression of Thrombospondinl (THBS1) in SA and DX5 cells --- p.128 / Chapter 4.3.3 --- Thrombospondinl (THBS1) cDNA transfection in DX5 cells --- p.130 / Chapter 4.3.4 --- mRNA expression of MDR1 in Thrombospondinl-transfected DX5 cells (DX5_THBS1) --- p.132 / Chapter 4.3.5 --- P-glycoprotein expression in Thrombospondinl-transfected DX5 cells --- p.134 / Chapter 4.3.6 --- "Cytotoxicity of doxorubicin (Dox) on DX5 control, DX5 vector control and DX5一THBS1 cells" --- p.136 / Chapter 4.3.7 --- "Doxorubicin (Dox) uptake by SA control, DX5 control and DX5_THBS1 cells" --- p.138 / Chapter 4.4 --- Discussion --- p.141 / Chapter 4.5 --- Conclusion --- p.145 / Chapter Chapter 5 --- General discussion --- p.146 / Chapter 5.1 --- Doxorubicin induced multidrug resistance in human uterin sarcoma cells via upregulation of P-glycoprotein --- p.147 / Chapter 5.2 --- The down-regulation of Ninjurin1 in human uterine sarcoma cells contributed to multidrug resistance --- p.148 / Chapter 5.3 --- The down-regulation of Thrombospondin1 in human uterine sarcoma cells contributed to multidrug resistance --- p.150 / Chapter 5.4 --- Conclusion and Future Perspective --- p.153 / Reference --- p.155

Cheung, Wing Ki. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 100-112). / Abstracts in English and Chinese. / Acknowledgments / Abbreviations / Abstract 一 English --- p.i / - Chinese --- p.iii / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Colon Cancer / Chapter 1.1.1. --- Colon cancer statistic in Hong Kong --- p.1 / Chapter 1.1.2. --- Development of Colon cancer --- p.1 / Chapter 1.1.3. --- Treatment --- p.2 / Chapter 1.2. --- Chemistry of ascorbates / Chapter 1.2.1. --- Sodium-L-ascorbate --- p.3 / Chapter 1.2.2. --- "Sodium 5,6-benazylidene-L-ascorbate" --- p.4 / Chapter 1.3. --- "Reactive oxygen species and reactive nitrogen species, and their biological consequences" --- p.5 / Chapter 1.4. --- Cell cycle --- p.7 / Chapter 1.5. --- Autophagy --- p.8 / Chapter 1.6. --- Human colon cancer HT29 cells for anti-tumor study --- p.9 / Chapter 1.7 --- Aim of study --- p.10 / Chapter Chapter 2 --- Comparative studies of cytotoxicity of SAA and SBA in short term treatment / Chapter 2.1. --- Introduction --- p.11 / Chapter 2.2. --- Materials and Methods --- p.14 / Chapter 2.3. --- Results --- p.17 / Chapter 2.4. --- Discussion --- p.26 / Chapter Chapter 3 --- Comparative studies of SAA and SBA in oxidative stress induction and their corresponding ROS inhibitors / Chapter 3.1. --- Introduction --- p.28 / Chapter 3.2. --- Materials and Methods --- p.31 / Chapter 3.3. --- Results --- p.35 / Chapter 3.4. --- Discussion --- p.42 / Chapter Chapter 4 --- "Effects of SAA and SBA treatments on cell cycle regulatory proteins and the induction of transient cell cycle arrests in Gl, S and G2 phases Cell Cycle" / Chapter 4.1. --- Introduction --- p.45 / Chapter 4.2. --- Materials and Methods --- p.49 / Chapter 4.3. --- Results --- p.53 / Chapter 4.4. --- Discussion --- p.69 / Chapter Chapter 5 --- Autophagy induction during SBA treatment and autophagy inhibition during SAA treatment / Chapter 5.1. --- Introduction --- p.72 / Chapter 5.2. --- Materials and Methods --- p.74 / Chapter 5.3. --- Results --- p.77 / Chapter 5.4. --- Discussion --- p.91 / Chapter Chapter 6 --- General Discussion --- p.93 / References --- p.100

Lau, Ka Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 223-237). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgments --- p.vi / Publication List --- p.vii / Table of Contents --- p.viii / List of Abbreviations --- p.xiv / List of Figures --- p.xvi / List of Tables --- p.xx / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Cancer --- p.1 / Chapter 1.1.1 --- Cancer in Hong Kong --- p.1 / Chapter 1.1.2 --- Different types of cancer treatments and the side effects --- p.4 / Chapter 1.1.3 --- Alternative therapies for cancer treatment --- p.6 / Chapter 1.1.3.1 --- Successful examples of anti-cancer drugs from traditional Chinese herbs --- p.7 / Chapter 1.2 --- Anti-tumor study approaches --- p.11 / Chapter 1.2.1 --- Direct cytotoxic activities --- p.12 / Chapter 1.2.2 --- Immunomodulatory activities --- p.14 / Chapter 1.2.3 --- Anti-angiogenesis activities --- p.16 / Chapter 1.3 --- Objectives of our study --- p.20 / Chapter Chapter 2 --- Background of selected Chinese herbs in our study / Chapter 2.1 --- Search for anti-tumor Chinese herbs --- p.21 / Chapter 2.1.1 --- Chinese herbs commonly used for cancer treatment --- p.21 / Chapter 2.1.2 --- Literature Search --- p.21 / Chapter 2.2 --- Results --- p.22 / Chapter 2.2.1 --- Lists of Chinese herbs from various Chinese medicine practitioners --- p.22 / Chapter 2.2.2 --- Selected traditional Chinese herbs from literature search --- p.22 / Chapter 2.2.3 --- Selected Chinese herbs for our study --- p.27 / Chapter 2.3 --- Background information of the five selected Chinese herbs --- p.28 / Chapter 2.3.1 --- Fructus Bruceae (FB) --- p.28 / Chapter 2.3.1.1 --- Traditional uses --- p.28 / Chapter 2.3.1.2 --- Previous Studies of Fructus Bruceae --- p.28 / Chapter 2.3.1.3 --- Isolated compounds of FB --- p.31 / Chapter 2.3.2 --- Cortex Phellodendri Amurensis (PA) --- p.35 / Chapter 2.3.2.1 --- Traditional uses --- p.35 / Chapter 2.3.2.2 --- Previous studies of Cortex Phellodendri Amurensis --- p.35 / Chapter 2.3.2.3 --- Previous studies of Berberine --- p.38 / Chapter 2.3.3 --- Radix et Rhizoma Asteris (RA) --- p.39 / Chapter 2.3.3.1 --- Traditional uses --- p.39 / Chapter 2.3.3.2 --- Previous Studies of Radix et Rhizoma Asteris --- p.39 / Chapter 2.3.4 --- Semen Coicis (SC) --- p.41 / Chapter 2.3.4.1 --- Traditional uses --- p.41 / Chapter 2.3.4.2 --- Previous Studies of Semen Coicis --- p.41 / Chapter 2.3.5 --- Radix Scrophulariae (RS) --- p.43 / Chapter 2.3.5.1 --- Traditional uses --- p.43 / Chapter 2.3.5.2 --- Previous Studies of Radix Scrophulariae --- p.43 / Chapter 2.4 --- Authentication of selected Chinese herbs --- p.45 / Chapter 2.4.1 --- Sources --- p.45 / Chapter 2.4.2 --- Morphological characteristics of the Chinese herbs --- p.47 / Chapter 2.4.2.1 --- Fructus Bruceae --- p.47 / Chapter 2.4.2.2 --- Cortex Phellodendri Amurensis --- p.48 / Chapter 2.4.2.3 --- Radix et Rhizoma Asteris --- p.49 / Chapter 2.4.2.4 --- Semen Coicis --- p.50 / Chapter 2.4.2.5 --- Radix Scrophulariae --- p.51 / Chapter 2.5 --- Extraction of selected Chinese herbs --- p.52 / Chapter 2.5.1 --- Materials and methods --- p.52 / Chapter 2.5.1.1 --- Preparation of aqueous extracts of selected Chinese herbs --- p.52 / Chapter 2.5.2 --- Results --- p.53 / Chapter 2.5.2.1 --- Percentage yield of aqueous extract of selected Chinese herbs --- p.53 / Chapter 2.6 --- Discussion --- p.54 / Chapter Chapter 3 --- Direct cytotoxic effect of selected Chinese herbs / Chapter 3.1 --- Background --- p.55 / Chapter 3.2 --- Materials and methods --- p.56 / Chapter 3.2.1 --- Cell cultures --- p.56 / Chapter 3.2.2 --- Determination of cell viability by MTT assay --- p.58 / Chapter 3.2.3 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.59 / Chapter 3.2.4 --- Preparation of etoposide for direct cytotoxic assay --- p.60 / Chapter 3.2.5 --- Statistical analysis --- p.61 / Chapter 3.3 --- Results --- p.62 / Chapter 3.3.1 --- Cytotoxic effects of five selected Chinese herbs on a panel of human cancer cell lines and human normal cell line --- p.62 / Chapter 3.3.2 --- Comparison of the cytotoxic effect of etoposide and the selected Chinese herbal extracts on a panel of human tumor cells --- p.72 / Chapter 3.3.3 --- Further investigations of the anti-tumor effect of PA --- p.75 / Chapter 3.3.3.1 --- Materials and methods --- p.75 / Chapter 3.3.3.1.1 --- Quantification of berberine chloride in PA aqueous extract using TLC --- p.75 / Chapter 3.3.3.1.2 --- Determination of cell viability by MTT assay --- p.76 / Chapter 3.3.3.2 --- Results --- p.76 / Chapter 3.3.3.2.1 --- Quantification of berberine chloride in PA aqueous extract using TLC --- p.76 / Chapter 3.3.3.2.2 --- Cytotoxic effect of berberine on a panel of human cancer cell lines --- p.78 / Chapter 3.4 --- Discussion --- p.80 / Chapter Chapter 4 --- Immunomodulatory effects of selected Chinese herbs / Chapter 4.1 --- Background --- p.84 / Chapter 4.2 --- Materials and methods --- p.87 / Chapter 4.2.1 --- Preparation of human peripheral blood mononuclear cells (huPBMCs) --- p.87 / Chapter 4.2.2 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.88 / Chapter 4.2.3 --- Preparation of cell mitogens --- p.88 / Chapter 4.2.4 --- Statistical analysis --- p.89 / Chapter 4.3 --- Results --- p.89 / Chapter 4.3.1 --- Mitogenic activities of the selected herbal extracts on huPBMCs --- p.89 / Chapter 4.4 --- Further investigations of the mitogenic activities of SC and RA extracts --- p.96 / Chapter 4.4.1 --- Materials and methods --- p.96 / Chapter 4.4.1.1 --- Preparation of human peripheral blood mononuclear cells (huPBMCs) --- p.96 / Chapter 4.4.1.2 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.96 / Chapter 4.4.2 --- Results --- p.97 / Chapter 4.4.2.1 --- Mitogenic effects of SC and RA aqueous extracts (in the presence of polymyxin B) --- p.97 / Chapter 4.5 --- Chemical characterization of RA aqueous extract --- p.100 / Chapter 4.5.1 --- Materials and methods --- p.100 / Chapter 4.5.1.1 --- Quantification of polysaccharide and carbohydrate contents in RA aqueous extract --- p.100 / Chapter 4.5.1.2 --- Quantification of protein content in RA aqueous extract --- p.101 / Chapter 4.5.2 --- Results --- p.103 / Chapter 4.5.2.1 --- Chemical characterization of RA aqueous extract --- p.103 / Chapter 4.6 --- Further investigations of the underlying mechanisms of the mitogenic activities of RA aqueous extract --- p.104 / Chapter 4.6.1 --- Materials and methods --- p.104 / Chapter 4.6.1.1 --- Preparation of human peripheral blood mononuclear cells (huPBMCs) --- p.104 / Chapter 4.6.1.2 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.104 / Chapter 4.6.1.3 --- Human Thl/Th2 Cytokine Cytometric Bead Array (CBA) --- p.105 / Chapter 4.6.1.4 --- Statistical analysis --- p.106 / Chapter 4.6.2 --- Results --- p.106 / Chapter 4.6.2.1 --- Effects of RA aqueous extract on productions of cytokinesin huPBMCs --- p.106 / Chapter 4.7 --- Discussion --- p.108 / Chapter Chapter 5 --- Anti-angiogenesis effects of selected Chinese herbs / Chapter 5.1 --- Background of in vivo zebrafish model --- p.112 / Chapter 5.2 --- Materials and methods --- p.117 / Chapter 5.2.1 --- Maintenance of zebrafish --- p.117 / Chapter 5.2.2 --- Collection of zebrafish embryos --- p.117 / Chapter 5.2.3 --- Zebrafish embryos treated with different herbal extracts --- p.117 / Chapter 5.2.4 --- Visual screens of zebrafish embryos using fluorescence microscopy --- p.118 / Chapter 5.2.5 --- Statistical analysis --- p.118 / Chapter 5.3 --- Results --- p.120 / Chapter 5.3.1 --- Anti-angiogenesis effect of SU5416 --- p.120 / Chapter 5.3.2 --- Anti-angiogenesis effects of selected herbal extracts on zebrafish model --- p.122 / Chapter 5.4 --- Discussion --- p.133 / Chapter Chapter 6 --- Further investigations on the anti-tumor effects of Fructus Bruceae and its sub-fractions / Chapter 6.1 --- Introduction --- p.136 / Chapter 6.2 --- Solvent partition of FB aqueous extract --- p.138 / Chapter 6.2.1 --- Materials and methods --- p.138 / Chapter 6.2.1.1 --- Solvent partition --- p.138 / Chapter 6.2.1.2 --- Thin layer chromatography of FB fractions --- p.138 / Chapter 6.2.2 --- Results --- p.139 / Chapter 6.2.2.1 --- Percentage yield of different fractions of FB aqueous extract --- p.139 / Chapter 6.2.2.2 --- Thin layer chromatography of FB fractions --- p.140 / Chapter 6.3 --- Investigations of the anti-tumor activities of FBW fraction --- p.141 / Chapter 6.3.1 --- Materials and methods --- p.141 / Chapter 6.3.1.1 --- Cell cultures --- p.141 / Chapter 6.3.1.2 --- Determination of cell viability by MTT assay --- p.141 / Chapter 6.3.1.3 --- Preparation of human peripheral blood mononuclear cells (huPBMCs) --- p.141 / Chapter 6.3.1.4 --- Determination of cell proliferation by tritiated thymidine incorporation assay --- p.141 / Chapter 6.3.1.5 --- Statistical analysis --- p.141 / Chapter 6.3.2 --- Results --- p.142 / Chapter 6.3.2.1 --- Cytotoxic effects of FBW on a panel of human cancer cells and human normal cells --- p.142 / Chapter 6.3.2.2 --- Mitogenic activities of FBW fraction on huPBMCs --- p.145 / Chapter 6.4 --- Chemical characterizations of FB aqueous extract and FBW fraction --- p.147 / Chapter 6.4.1 --- Materials and methods --- p.147 / Chapter 6.4.2 --- Results --- p.147 / Chapter 6.5 --- Bioassay guided fractionation of FBW --- p.149 / Chapter 6.5.1 --- Fractionation using macroporous resin column (D101) --- p.149 / Chapter 6.5.2 --- Investigations of the anti-tumor effects of the sub-fractions of FBW --- p.151 / Chapter 6.5.2.1 --- Direct cytotoxic effects of FBW sub-fractions on NB-4 cells and human normal cells --- p.151 / Chapter 6.5.2.2 --- Immunomodulatory effects of FBW-DH sub-fraction --- p.154 / Chapter 6.5.3 --- Fractionation using ethanol precipitation --- p.155 / Chapter 6.5.3.1 --- Chemical characterization of sub-fractions of FBW-DH --- p.156 / Chapter 6.5.3.2 --- "Direct cytotoxic effects of 50P, 80P and 80S on NB-4 cells and human normal cells" --- p.159 / Chapter 6.5.3.2.1 --- DNA agarose gel electrophoresis --- p.163 / Chapter 6.5.3.2.2 --- Cell death detection ELISA --- p.166 / Chapter 6.5.3.2.3 --- ELISA of apoptotic related proteins --- p.168 / Chapter 6.5.3.2.4 --- Telomerase PCR ELISA --- p.176 / Chapter 6.5.3.3 --- "Immunomodulatory effects of 50P, 80P and 80S" --- p.178 / Chapter 6.5.3.3.1 --- Human Thl/Th2 cytokine cytometric bead array (CBA) --- p.180 / Chapter 6.5.3.3.2 --- Limulus Amebocyte Lysate assay --- p.183 / Chapter 6.5.3.4 --- "Anti-angiogenic effects of 50P, 80P and 80S" --- p.184 / Chapter 6.5.3.5 --- Liquid chromatography mass spectrometry (LCMS) analysis of 50P --- p.192 / Chapter 6.6 --- Discussion --- p.194 / Chapter Chapter 7 --- General discussions and conclusions / Chapter 7.1 --- Anti-tumor activities of five selected Chinese herbs --- p.202 / Chapter 7.2 --- Significance of the present study --- p.213 / Chapter 7.3 --- Limitations of our study --- p.214 / Chapter 7.4 --- Future work --- p.215 / Appendices / Appendix I Phenol-sulphuric acid spectrophotometric assay --- p.216 / Appendix II Bradford assay --- p.217 / Appendix III Calibration curves of cytokines in CBA assay --- p.218 / Appendix IV Endotoxin standard curve --- p.220 / Appendix V LCMS data of two chemical markers of FB --- p.221 / Bibliography --- p.223

Lectins (hemagglutinins) are a type of proteins that could recognize different sugar structures and specifically initiate reversible binding with them. Though they have been universally found in a variety of organisms, they are exceptionally abundant in legumes. From the initial finding of agglutinating red blood cells to the discovery of recognizing carbohydrates on cell membranes, multiple functions of lectins have been gradually unveiled by numerous researchers across a century. Based on its carbohydrate-binding property, lectins have found great value in the study of glycomics. Many lectin-based biological tools, like lectin affinity chromatography, lectin blotting, lectin histochemistry, lectin microarray and lectin-based biosensor have been developed and applied to the study of glycoproteins. Besides, lectins are also reported to be potential agents for anti-insect, anti-fungi, anti-HIV, anti-bacterial and anti-tumor applications. / The present study focuses on the isolation of a new hemagglutinin from an edible legume, exploration of its anti-colorectal cancer effect and mechanisms, its cytokine inducing function and anti-HIV activities. The protein was purified by liquid chromatography techniques which entailed affinity chromatography on Affi-Gel Blue Gel, ion exchange chromatography on Mono Q and gel filtration on Superdex 75 with an FPLC system. The hemagglutinating activity of this hemagglutinin was demonstrated to be ion-dependent and stable over a wide range of temperatures (20-60℃) and pH (2-11) values. Like most of the lectins or hemagglutinins, this novel hemagglutinin could also attenuate the activity of HIV-1 reverse transcriptase. / This hemagglutinin could potently suppress the proliferation of colorectal carcinoma HCT116 cells and colorectal adenocarcinoma HT29 cells. It induced cell cycle arrest in G0/G1 phase, downregulated the expression of Cyclin D1 and upregulated P21expression. The protein initially bound on the cell membranes most probably through glycoproteins and subsequently entered the cytoplasm, which was achieved as early as 3h post treatment. The hemagglutinin was found to be preferentially localized in Golgi apparatus and initiated aggregation of the Golgi apparatus, which may possibly attenuate its protein processing capacity by reducing total superficial area or even partially blocking the transportation of proteins from the endoplasmic reticulum (ER). The impaired protein reception ability of Golgi apparatus may lead to the protein accumulation in the ER and induce cell apoptosis. Accordingly, two ER stress sensors (IRE1α and ATF6) and one late product of ER stress (CHOP) were found to up-regulated. Apoptosis-inducing effect of this hemagglutinin on HT29 and HCT116 cells were further confirmed using methods based on different principles. Cells treated with the hemagglutinin were observed to undergo obvious chromatin condensation, mitochondrial membrane depolarization and phosphatidylserine exposure. An apoptosis initiator (Apaf-1) and one important indicator (cleaved PARP) of cell apoptosis were accordingly detected. Besides, intraperitoneal administration of this hemagglutinin to colorectal tumor bearing nude mice could slow down the growth of tumors. / At last, this hemagglutinin exerted an immunomodulatory function on splenocytes by stimulating the mRNA expression level of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), interferon- gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α). Secretion of IL-1β and IL-2 from splenocytes also increased with the concentration of this hemagglutinin. / In a short conclusion, we have isolated a new hemagglutinin with anti-HIV RT, anti-colorectal cancer and immunomodulatory activities. / 凝集素（血凝素）是一类能够识别不同糖结构并能和它们发生可逆性结合的蛋白。虽然他们在许多生物体内均有发现，但这类蛋白在豆科植物中的含量尤其丰富。经过一个多世纪来众多研究者的努力，从最初认识到其具有红血细胞凝集功能到糖类识别作用，凝集素的诸多功能已被逐步挖掘。基于其独特的糖结构识别特性，凝集素在糖组学的研究中具有重大意义。许多基于凝集素的生物方法，如凝集素亲和层析法，凝集素印迹法，凝集素组织化学，凝集素生物芯片以及基于凝集素的生物传感器已被研究出来, 并用于研究糖蛋白。除此之外，研究表明，凝集素还具有抗虫，抗真菌，抗HIV，抗细菌和抗癌等活性。 / 该凝集素可以极大抑制结肠直肠癌HCT116细胞和结直肠腺癌HT29细胞增殖，引发细胞周期停滞，分别下调和上调Cyclin D1和P21的表达。该蛋白极有可能首先通过和细胞表面的糖蛋白结合而附在细胞膜上，然后进入细胞内。该过程可在往细胞培养液内加入该蛋白后的3小时内完成。该凝集素优先与细胞内的高尔基体结合，随后引发高尔基体聚集。该聚集作用可能会通过减少高尔基体总表面积甚至阻塞内质网和高尔基体间的蛋白运输，进而减弱高尔基体处理蛋白质的能力。当高尔基体接受蛋白的能力降低时，蛋白可能会堆积在内质网上并进一步引发细胞程序性死亡。相应地，两个内质网应激感受蛋白IRE1α和 ATF6以及内质网应激后期产物CHOP均被发现上调。该凝集素对HT29细胞和HCT116细胞的凋亡诱导作用采用不同的方法进行了进一步的确认，这些方法都是基于不同检测原理进行的。结果表明，该凝集素可导致细胞产生明显的染色质凝缩，线粒体膜电位去极化和磷脂酰丝氨酸外翻。与此相应地，凋亡启动蛋白Apaf-1和凋亡后期蛋白(被剪切的PARP)可在处理后的细胞中检测到。通过腹腔注射的方法给接种大肠癌细胞的裸鼠给药可降低肿瘤的生长速度。 / 本研究的工作包括：从一种可食用豆类中提取一种新的凝集素；检测其抗大肠癌的作用和机制；研究其细胞素诱导作用以及抗HIV活性。该蛋白采用液相色谱法分离提纯，其中包括亲和层析柱Affi-Gel Blue Gel, 离子交换层析柱Mono Q 和凝胶层析柱Superdex 75，后两种层析法在FPLC系统上操作。该蛋白的红血细胞凝集作用具有金属阳离子依赖性，并在20-60℃和pH2-11范围内保持活性稳定。像许多其它的凝集素一样，该蛋白也可以削弱HIV逆转录酶活性。 / 最后，该蛋白还具有免疫调节作用，它可促进白细胞介素-2，白细胞介素-6，白细胞介素-1β，干扰素-γ和肿瘤坏死因数-α在mRNA水平上的表达并刺激白细胞介素-2和细胞介素-1β的分泌。 / 综上所诉，本研究分离提纯了一种新凝集素，它具有抗HIV，抗大肠癌和免疫调节作用。 / Dan, Xiuli. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 153-170). / Abstracts also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

OBJETIVO: Avaliar a eficácia e segurança da imunoterapia tópica com imiquimode creme 5% no tratamento do carcinoma basocelular nodular periocular. MÉTODOS: Pacientes com carcinoma basocelular confirmado por biopsia e com contraindicação clínica para a cirurgia reconstrutiva devido ao alto risco ou que recusaram a cirurgia por razões estéticas ou fobia foram incluídos no estudo. O tratamento foi iniciado após treinamento do paciente e de acompanhante. A posologia foi de 5 vezes por semana por 8 a 16 semanas. Acompanhamento quinzenal foi realizado durante a vigência do tratamento com questionário, exame biomicroscópico, medida da acuidade visual e documentação fotográfica. As características clínicas das lesões foram mensuradas através do software ImageJ. Após 12 semanas do fim da terapia, uma nova biópsia na região da lesão foi guiada por fotografia. O seguimento dos pacientes foi semestral, após fim do tratamento, com biópsias anuais da região até o presente momento. RESULTADOS: 19 foram tratadas. A taxa de cura histológica foi de 89,5% após três meses do final do tratamento, e de 84,2% nos três anos de seguimento (39,5 meses). A taxa de cura histológica em três anos foi de 100% para lesões menores que 10 mm, e de 81,8% para lesões maiores que 10 mm. De uma forma geral, os efeitos colaterais da medicação foram mais frequentes durante as oito primeiras semanas de tratamento. Quanto menor foi a distância da lesão à margem palpebral, maior foi chance de o paciente desenvolver ectrópio no tratamento (p = 0,045). Assim, como quanto maior foi a inflamação, maior foi a chance de desenvolver ectrópio, dor e edema durante o tratamento (p = 0,017, p = 0,016 e p = 0,044, respectivamente). CONCLUSÕES: Imiquimode creme 5% mostrou-se eficaz para o tratamento alternativo do carcinoma basocelular periocular, principalmente em lesões menores que 10 mm. Em adição, demonstrou um interessante efeito neoadjuvante sobre as lesões maiores que 10 mm que não foram curadas. Mostrou-se um tratamento seguro; entretanto, um cuidado maior deve ser dado às lesões próximas à margem palpebral devido ao maior risco de complicações e desenvolvimento de ectrópio / Objective: to evaluate the efficacy and safety of topical administration of 5% imiquimod cream in the treatment of periocular nodular basal cell carcinoma (BCC). Methods: Patients with periocular nodular basal cell carcinoma confirmed by biopsy and clinical contraindication to reconstructive surgery due to high risk or who decline surgery for aesthetic reasons or phobia were included in the study. The medication was applied once a day, five days a week for 8-16 weeks. Treatment was initiated after provision of patient and caretaker training. During treatment, patients were followed up twice a month with questionnaires, biomicroscopic examinations, measurement of visual acuity and photographic documentation. The clinical characteristics of the tumors were registered with the software ImageJ. Twelve weeks after the end of treatment, an image-guided biopsy of the tumor site was performed. Patients have since been attending follow-up visits every six months, and biopsies of the region are performed annually. Results: 19 tumors were treated with imiquimod. The average histological cure rate was 89.5% after 3 months at the end of the treatment and 84.2% after 3 years of follow-up (39.5 months). The 3-year histological cure rate was 100% for smaller tumors and 81.8% for larger tumors (>10 mm). In general, drug-related side effects were more frequent during the first 8 weeks of treatment. The smaller the distance between tumor and lid margin, the greater the probability of developing ectropion during treatment (p=0.045). Likewise, the more severe the inflammation, the greater the probability of developing ectropion, pain and edema during treatment (p=0.017, p=0.016 and p=0.044 respectively). Conclusion: Topical administration of 5% imiquimod cream was found to be an efficacious and relatively safe alternative treatment for periocular BCC, especially for tumors smaller than 10 mm, with interesting neoadjuvant effects on uncured tumors larger than 10 mm. However, special care is required when treating tumors near the eyelid margin due to the risk of complications and development of ectropion