Yeung Chung Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 83-97). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese) --- p.iv / Acknowledgements --- p.vii / Table of contents --- p.ix / List of figures --- p.xii / List of tables --- p.xiv / List of abbreviations --- p.xv / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Literature Review --- p.5 / Chapter 1.2.1 --- Cancer and melanoma --- p.5 / Chapter 1.2.2 --- Anticancer drugs from natural products --- p.6 / Chapter 1.2.3 --- Challenges in treatment of melanoma --- p.9 / Chapter 1.2.4 --- TCM - New source of natural products for cancer therapy --- p.10 / Chapter 1.2.6 --- The genus Schefflera --- p.11 / Chapter 1.2.7 --- Anticancer activities of triterpenoids --- p.16 / Chapter 1.2.8 --- Cancer and apoptosis --- p.17 / Chapter 1.2.8.1 --- The Apoptosis Pathways --- p.20 / Chapter 1.2.9 --- Studies of anticancer molecules against melanoma --- p.26 / Chapter 1.2.9.1 --- In vitro models for studying anticancer molecules --- p.26 / Chapter 1.2.9.2 --- In vivo models for studying anticancer molecules --- p.30 / Chapter Chapter 2 --- Materials and Methods --- p.34 / Chapter 2.1 --- Phytochemicals --- p.34 / Chapter 2.2 --- "Chemicals, Cell Lines and Culture Conditions" --- p.34 / Chapter 2.3 --- Determination of in vitro antiproliferative effects of HLDA and the ethyl acetate fraction from S. heptaphylla on human cancer cells --- p.36 / Chapter 2.3.1 --- MTT assay --- p.36 / Chapter 2.4 --- Determination of the in vitro antiproliferative mechanisms of HLDA and the ethyl acetate fraction from S. heptaphylla in human melanoma A375 cells --- p.37 / Chapter 2.4.1 --- Flow cytometric analysis --- p.37 / Chapter 2.4.2 --- Western blot analysis --- p.38 / Chapter 2.5 --- Determination of the in vivo anticancer effects of the ethyl acetate fraction from S. heptaphylla --- p.41 / Chapter 2.5.1 --- Determination of cancer chemopreventive effect of the ethyl acetate fraction with DMBA/TPA-induced skin carcinogenesis model --- p.41 / Chapter 2.5.2 --- Determination of cancer therapeutic effect of the ethyl acetate fraction with athymic BALB/c nude mice model --- p.42 / Chapter 2.6 --- Statistical Analysis --- p.44 / Chapter Chapter 3 --- Results --- p.45 / Chapter 3.1 --- Effects of HLDA and the ethyl acetate fraction on viability and proliferation of different cancer cell lines by MTT assay --- p.45 / Chapter 3.2 --- Effects of HLDA and the ethyl acetate fraction on cell cycle and apoptosis in A375 cells determined by DNA flow cytometry --- p.46 / Chapter 3.3 --- Effects of HLD A and the ethyl acetate fraction on apoptosis induction in A375 cells determined by Western blotting --- p.53 / Chapter 3.4 --- Effects of HLD A and ethyl acetate fraction on caspases in A375 cells --- p.55 / Chapter 3.5 --- Effects of caspase inhibitors on the HLDA- and the ethyl acetate fraction-induced apoptosis in A375 cells --- p.57 / Chapter 3.6 --- Effects of HLD A and the ethyl acetate fraction on the expression of Bcl-2 family proteins in A375 cells --- p.62 / Chapter 3.7 --- Chemopreventive effect of the ethyl acetate fraction from S. heptaphylla on the DMBA/TPA-induced skin carcinogenesis model --- p.65 / Chapter 3.8 --- Chemotherapeutic effect of the ethyl acetate fraction from S. heptaphylla on A375 xenograft in athymic nude mice --- p.70 / Chapter Chapter 4 --- Discussion --- p.73 / References --- p.83

Different cucurbitacin derivatives have been compared for the gamma globin induction potential. Cucurbitacin D turned out to be the most potential inducer among the derivatives had been tested. Later I had screened more herbs for the gamma globin induction activities. One of the herbs showed a higher activity than Fructus Trichosanthis, which could be the potential candidate to isolate more potent inducer. In the toxicity study, cucurbitacin D only have a mild toxic effect on the normal cell lines and transgenic mice. Finally, the efficacy of cucurbitacin D was tested on a sickle cell anemia mouse model and demonstrated a significant induction of fetal haemoglobin production. Cucurbitacin D may be a potential drug candidate for treating beta globinopathies. / Thalassemia is a global disease. It was report in 2001 that there were 270 million people who carried the severe disease. Most of the cases were found in Africa and south-east Asia. China has a high incidence rate of 0.66% in 2001. In the past, the treatments of the disease were blood transfusion and bone marrow transplantation. However, many defects in such kinds of treatments were reported. The balance of relieving the syndrome of the disease and the adverse effects of the drugs was the consideration to the physician. The drug, hydroxyurea, can activate the gamma globin gene and produce hemoglobin F to replace the beta globin as an oxygen transporter is considered as an better treatment to ameliorate the syndrome. Safety and effectiveness in the long-term treatment using hydroxyurea are questionable. Cucurbatacin D purified from a Chinese herb demonstrates 2000 folds more potent than hydroxyurea. It can activate the gamma globin gene and produce hemoglobin F shown in ELISA and confocal microscopy. The fundamental work for drug development is carrying out through this project. In this project the biological property and toxicity were studied. / Liu, Shuk Ming. / Adviser: M.C. Tung. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 245-270). / 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.

Liu, Kan. / "November, 2010"--Abstract. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 116-129). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A pesquisa para o desenvolvimento de novas drogas quimioterápicas, tem se baseado nas propriedades dos produtos de origem natural. Estudos experimentais em animais indicam que o álcool perílico (AP), um monoterpeno originalmente isolado dos óleos essenciais de várias plantas é capaz de causar a regressão de diferentes tipos de tumores. O tratamento clássico preconizado para os astrocitomas anaplásicos e glioblastoma multiforme consiste de: ressecção cirúrgica, radioterapia e/ou quimioterapia e raramente apresentam efeito curativo. O presente trabalho teve como objetivo analisar o efeito do AP na proliferação, na alteração da morfologia, na síntese de proteínas e migração celular de diferentes linhagens de glioblastoma murino e humano. Foram utilizados modelos in vitro de cultivo de células e ensaios in vivo de migração celular. O tratamento in vitro com o AP nas concentrações v/v de 0,003%, 0,02%, 0,03%, 0,3%, 3% e 30% nas linhagens de glioblastoma C6 de murinos e linhagens A172 e U87MG de glioblastoma humano, mostrou que mesmo nas concentrações (v/v) mais baixas (0,03% e 0,3%) o AP promove a inibição da proliferação celular e da síntese de proteínas. O tratamento in vitro com o AP a 0,3% v/v causou após 15 minutos perda da permeabilidade celular e mais tardiamente, 50 minutos, alterações acentuadas na citoarquitetura das linhagens C6, U87MG e A172. Nos ensaios in vivo com ovos embrionados, o tratamento com o AP nas concentrações v/v 0,3% e 0,03% causou efeito inibitório na migração celular da linhagem C6. Os resultados sugerem uma eficácia quimioterápica do AP na citotoxidade e na inibição da migração celular de linhagens de glioblastoma murino e humano. / The search for new chemotherapeutic drugs has increased, especially for those that have a natural origin. Perillyl alcohol (POH), is a naturally occurring monoterpene, found in the essential oils of citrus fruits and other plants, with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. Standard treatment of anaplastic gliomas and glioblastoma multiforme consisting of surgical resection, radiation therapy and/or chemotherapy is rarely curative. This work aimed to evaluate in vitro and in vivo effects of POH treatment, cell proliferation, changes in morphology, protein synthesis, and migration of distinct lineage of glioblastoma cells. It was chosen in vitro culture systems and in vivo assays for assessing cellular migration. In vitro treatment of POH at concentrations of (v/v) 0.003%, 0.02%, 0.03%, 0.3%, 3% and 30%, consistently inhibited proliferation of murine C6 and human A172 and U87MG of glioblastoma cells. In vitro treatment of POH at low concentrations 0.03% v/v and 0.3% v/v also produced marked changes in cell morphology and inhibited protein synthesis. Likewise in vitro assays with 0.3% v/v POH treatment for 15 minutes, initially caused marked alteration in membrane permeability and later (50 minutes) drastic changes in the cytoarchitecture of C6, U87MG and A172 cells. Furthermore, previous in vitro treatment of glioblastoma cells with 0.3% v/v and 0.03% v/v POH showed inhibition of cell migration and anti-metastatic activity in the in vivo model of the chick embryo with C6 cell line. Such results indicate the chemotherapeutic action of POH by promoting cytotoxicity and arresting migration of murine and human glioblastoma cell lines