Pang Siu Kwong. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 181-191) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common clinical problem. Tanshinone IIA is a compound purified from the Chinese herb Danshen ( Radix Salviae Miltiorrhiza Bge). Thrombopoietin (TPO) and Erythropoietin (Epo) are hematopoietic growth factors. The effects of tanshinone IIA, EPO and TPO on hypoxia-ischemia brain injury were investigated in this study, using in vitro model of neural cell culture and an in vivo model of hypoxic-ischemic brain damage. / Our observation provided the first evidence showing the expression of functional TPO receptor c-mpl in central nervous system. It revealed that novel agents TPO, EPO and tanshinone IIA have neuroprotection effects against brain injury induced by hypoxia-ischemia in neonatal rats, and these agents could be developed for clinical applications. / To investigate the effect of TPO, EPO and tanshinone IIA on in-vivo neural protection, a neonatal rat model of hypoxic-ischemic brain damage was established. Our results demonstrated significant and sustained brain injury in the hypoxic-ischemic and vehicle-treated group, measured by the reduction in relative weights of the ipsilateral (right) to the contralateral (left) brain at 1 and 3 weeks post-surgery, compared with those of sham-operated animals. At 3 weeks post-surgery, the hypoxic-ischemic animals had decreased cortical neuron density quantified by neuron-specific enolase (NSE) staining, and compromised sensorimotor functions in response to the postural reflex test. Treatment with TPO, EPO and tanshinone IIA significantly reduced the severity of brain injury, as indicated by the significantly increased ipsilateral brain weight and neuron density. Recoveries of sensorimotor functions (p < 0.05) and histopathology were also observed in animals that received TPO, EPO and tanshinone IIA. The plasma of tanshinone IIA-treated animals exhibited higher antioxidant activities (oxygen radical absorbance capacity assay) than those from vehicle-treated rats. / TPO and TPO receptor (c-mpl) mRNA was identified in human cerebral hemispheres, cerebellum, mouse neural progenitor cell line C17.2 and four neuroblastoma cell lines (SK-N-MC, MHH-NB-11, SK-N-AS and SH-SY-5Y) using RT-PCR methods. TPO proteins were detected in human cerebrospinal fluid (CSF) and plasma by ELISA. Furthermore, TPO receptor c-mpl was confirmed in human cerebral hemispheres, hippocampus, cerebellum, brainstem and spinal cord using immunohistostaining. TPO had a stimulating effect on the growth of neural progenitor cell C17.2 in culture via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway as demonstrated by Western blot. The anti-apoptotic effects of TPO, EPO on C17.2 cells were demonstrated by staining with Annexin-V and PI. EPO exerted a protective effect against SHSY-5Y cell damage induced by NMDA (N-methyl-d-aspartate), as demonstrated by the MTT and LDH assay. The anti-oxidative property of tanshinone IIA was studied in the C17.2 cell line. Tanshinone IIA increased the viability of these cells subjected to 2,2'-azobis (2-amidino propane hydrochloride) (AAPH)-induced oxidative stress. / by Xia Wen-Jie. / "May 2005." / Advisers: Kwok-Pui Fung, Tai-Fai Fok. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0126. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 126-146). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Bioassays of total alkaloids of S. tuberosa samples representing the four types of chemical profiles were conducted on guinea pigs using citric acid aerosol for inducing cough. These results demonstrated their antitussive properties and thus suggested the possibility of other antitussive alkaloids than neotuberostemonine in S. tuberosa. So it became necessary to identify the major components in the samples of S. tuberosa representing the four types of chemical profiles. / Bioassays on guinea pigs of the four major components of S. tuberosa demonstrated their antitussive properties. Except a lower potency in tuberostemonine, antitussive effects of croomine and stemoninine showed similar or even stronger potency than neotuberostemonine at 25 and 50 mg/kg by intragastric administration. These four antitussive alkaloids could be used as lead compounds for the development of new antitussive drugs and as bioactive markers in quality control of the herb S. tuberosa and related products. / Cough is an airway defensive reflex, which is responsible for keeping the airway free of obstruction and harmful substances. As the commonest symptom for which medical advices is sought, enormous costs are spent on cough treatments. Regretfully, currently used antitussives are less than satisfactory due to their low potency or obvious side effects. So it is necessary to continue developing new and better antitussives. / Electrical stimulation of the superior laryngeal nerve on guinea pigs at 100 mg/kg through intraperitoneal administration indicated that croomine acted on the central pathway of cough reflex accompanied by respiratory depression. On the other hand, neotuberostemonine, tuberostemonine and stemoninine acted on the peripheral pathway without any observable side effects. These three alkaloids could be promising for developing new peripherally acting antitussives. Further, tuberostemonine was tested on primary cultured nodose ganglion cells by patch clamp and, at 0.5 mM, was demonstrated to significantly decrease the change amplitude of membrane potential induced by 1.0 mM citric acid solution. The results suggested that tuberostemonine could depress electrical excitability of nodose ganglion cells and thus inhibit the afferent signals of cough reflex leading to its antitussive activity. / In order to determine if the different chemical profiles of Stemona total alkaloids were the result of species difference or variations within the same species, the three Stemona species registered in the PRC Pharmacopoeia were collected from different areas in China. They were planted to flowering in our greenhouse and authenticated by both reproductive and vegetative characters. Microscopic examination on these authentic species showed that tuberous roots of S. tuberosa differed by epidermal cells with smooth outer surface and fibers in the cortex and pith from those of S. japonica and S. sessilifolia. The chemical profiles of authentic samples were analyzed on a HPLC-ELSD system. The results indicated that species-specific differences were present in the HPLC profiles of the three Stemona species. Within S. tuberosa, the chemical profiles of different samples were found to be very variable and they could be roughly divided into four types in the tested samples. Neotuberostemonine was present in one of the four types of S. tuberosa. Since antitussive effects of neotuberostemonine were demonstrated by Chung et al. (2003), it became necessary to determine if the samples containing alkaloids other than neotuberostemonine had antitussive properties. / The Chinese herb Radix Stemonae (Baibu) has long been used as an antitussive in Chinese medicine for some two thousand years. Its source materials, according to the Pharmacopoeia of the People's Republic of China (PRC Pharmacopoeia), come from the tuberous roots of three Stemona species, namely, S. japonica (Blume) Miq., S. sessilifolia (Miq.) Miq. and S. tuberosa Lour. However, hardly any experimental study is available to document their antitussive functions. Chung et al. (2003) reported that the antitussive components of S. tuberosa were neotuberostemonine and related stenine type Stemona alkaloids. And the antitussive potency of neotuberostemonine through intraperitoneal administration was reported to be comparable to codeine but not involving opioid receptors. In continuation with the study of the antitussive properties of the herb, it was found that total alkaloids of different samples of the herb appeared to vary in chemical profiles, whereas neotuberostemonine was found in only a few samples. / The major components of S. tuberosa including stemoninine, croomine and neotuberostemonine were isolated and determined by spectroscopic methods. It was the first time to isolate croomine from Stemona species, lending support to retaining the two genera Stemona and Croomina in the family Stemonaceae according to chemotaxonomy. Tuberostemonine, another major component of S. tuberosa was also isolated and determined in our team. Neotuberostemonine and tuberostemonine were two isomers but mutually exclusive in our tested samples. Moreover, these major components of S. tuberosa belonged to three types in molecular structure. Stemoninine was stemonamide type, croomine tuberostemospironine type and both neotuberostemonine and tuberostemonine stenine type. These results suggested that antitussive effects of S. tuberosa might be related to the components belonging to these three molecular types. / Xu Yantong. / "March 2006." / Adviser: Paul But. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6231. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 137-155). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Chan Wai-Lung, William. / Thesis submitted in: December 2000. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 124-131). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese Version) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.xii / List of Abbreviations --- p.xvi / Chapter 1 --- Introduction --- p.1 / Literature Review --- p.4 / Chapter 1.1 --- A Brief Introduction of Cancer --- p.4 / Chapter 1.2 --- Natural Products as a Drug --- p.5 / Chapter 1.2.1 --- Development of terrestrial plants as a drug --- p.6 / Chapter 1.2.1.1 --- Anticancer drugs from terrestrial plants and Chinese medicinal herbs --- p.7 / Chapter 1.2.2 --- Development of marine organisms as a drug --- p.8 / Chapter 1.2.2.1 --- Anticancer drugs from marine organisms --- p.9 / Chapter 1.3 --- Anticlastogenic Study - an Anticancer Study --- p.10 / Chapter 1.3.1 --- Anticlastogenesis mechanisms study --- p.11 / Chapter 1.3.2 --- In vivo anticlastogenic study --- p.13 / Chapter 1.4 --- Anticlastogenic Study of Chinese Medicinal Herbs and Marine Algae --- p.17 / Chapter 1.4.1 --- Selection of nine Chinese medicinal herbs and three marine algae for anticlastogenic screening --- p.18 / Chapter 1.5 --- Methods of Investigation --- p.20 / Chapter 1.5.1 --- Extraction methods --- p.20 / Chapter 1.5.2 --- Single cell gel electrophoresis (Comet assay) --- p.21 / Chapter 2 --- Materials and Methods --- p.27 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- Chinese medicinal herbs --- p.27 / Chapter 2.1.2 --- Marine algae --- p.27 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.1.4 --- Chemicals and solutions --- p.28 / Chapter 2.2 --- Methods --- p.31 / Chapter 2.2.1 --- Crude extraction of natural products --- p.31 / Chapter 2.2.1.1 --- Water extraction of Chinese herbs --- p.31 / Chapter 2.2.1.2 --- Water extraction of marine algae --- p.31 / Chapter 2.2.2 --- Test for the effective dosage of clastogen ethyl methanesulfonate (EMS) to BALB/c mice --- p.31 / Chapter 2.2.2.1 --- In vitro test --- p.32 / Chapter 2.2.2.2 --- In vivo test --- p.32 / Chapter 2.2.3 --- Anticlastogenic bioassays --- p.33 / Chapter 2.2.3.1 --- In vitro anticlastogenic screening --- p.33 / Chapter 2.2.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.33 / Chapter 2.2.3.3 --- In vivo anticlastogenic screening --- p.34 / Chapter 2.2.3.4 --- Different in vivo anticlastogenic treatment schedules --- p.35 / Chapter 2.2.4 --- Single cell gel electrophoresis assay (Comet assay) --- p.36 / Chapter 2.2.5 --- White blood cell viability determination --- p.37 / Chapter 2.2.6 --- Statistical analysis --- p.38 / Chapter 3 --- Results --- p.40 / Chapter 3.1 --- Extraction amount of different natural products and cell viability checking --- p.40 / Chapter 3.1.1 --- Chinese medicinal herbs --- p.40 / Chapter 3.1.2 --- Seaweeds --- p.40 / Chapter 3.1.3 --- Cell viability --- p.42 / Chapter 3.2 --- Effective dosage of clastogen EMS to BALB/c mice peripheral white blood cells --- p.42 / Chapter 3.2.1 --- In vitro --- p.42 / Chapter 3.2.2 --- In vivo --- p.42 / Chapter 3.3 --- In vitro anticlastogenic screen test and mechanisms investigation --- p.44 / Chapter 3.3.1 --- In vitro anticlastogenic screen test --- p.44 / Chapter 3.3.1.1 --- Chinese herbs --- p.44 / Chapter 3.3.1.2 --- Seaweeds --- p.53 / Chapter 3.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.55 / Chapter 3.3.2.1 --- H. dilatata --- p.56 / Chapter 3.3.2.2 --- S. angustifolium --- p.56 / Chapter 3.3.2.3 --- S. siliquastrum --- p.63 / Chapter 3.4 --- In vivo anticlastogenic screen test and mechanisms investigation --- p.66 / Chapter 3.4.1 --- In vivo anticlastogenic screen test --- p.66 / Chapter 3.4.1.1 --- Chinese herbs --- p.66 / Chapter 3.4.1.2 --- Seaweeds --- p.73 / Chapter 3.4.2 --- Different treatment methods in in vivo anticlastogenic test --- p.86 / Chapter 3.4.2.1 --- Simultaneous application method --- p.86 / Chapter 3.4.2.2 --- Pre-drug treatment method --- p.91 / Chapter 3.4.2.3 --- Post drug treatment method --- p.91 / Chapter 4 --- Discussion --- p.94 / Chapter 4.1 --- Cell viability and water extracts in Chinese medicinal herbs and marine algae --- p.94 / Chapter 4.2 --- Clastogenic effect of EMS to pWBCs of BALB/c mice --- p.94 / Chapter 4.3 --- In vitro anticlastogenic screen test of nine water extracts of Chinese medicinal herbs and three water extracts of marine algae --- p.99 / Chapter 4.4 --- In vitro anticlastogenic mechanisms investigation of three \03 marine algae extracts --- p.103 / Chapter 4.5 --- In vivo anticlastogenic screen test of Chinese herbs extracts and seaweeds extracts --- p.108 / Chapter 4.6 --- Different administration methods in in vivo anticlastogenic test --- p.115 / Chapter 4.6.1 --- Intraperitoneal route of administration --- p.115 / Chapter 4.6.2 --- In vivo pre- and post-treatment methods --- p.116 / Chapter 5 --- Summary and Conclusion --- p.120 / References --- p.124

Wong, Ka Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 177-189). / Abstracts in English and Chinese; includes Chinese. / Abstract --- p.i / 摘要 --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vii / List of Appendices --- p.xi / List of Tables --- p.xii / List of Figures --- p.xiv / Abbreviations --- p.xvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Background to the study --- p.2 / Chapter 1.2.1 --- Epidemiology of cancer --- p.2 / Chapter 1.2.1.1 --- Incidence and mortality in the World --- p.2 / Chapter 1.2.1.2 --- Incidence and mortality in Hong Kong --- p.4 / Chapter 1.2.2 --- Prevalence of Traditional Chinese Medicine (TCM) --- p.5 / Chapter 1.2.3 --- Prevalence of Traditional Chinese Medicine (TCM) in cancer --- p.6 / Chapter 1.2.4 --- Development of TCM in Hong Kong --- p.7 / Chapter 1.3 --- Theoretical rationale of the study --- p.8 / Chapter 1.4 --- Significance of the study --- p.11 / Chapter Chapter 2 --- Literature Review --- p.13 / Chapter 2.1 --- Introduction --- p.13 / Chapter 2.2 --- The concept of Advanced Cancer --- p.13 / Chapter 2.2.1 --- Pathology of Advanced Cancer --- p.14 / Chapter 2.2.1.1 --- Metastatic Cancer --- p.14 / Chapter 2.2.2 --- Sign and Symptoms of Advanced Cancer --- p.19 / Chapter 2.2.3 --- Diagnosis of Advanced Cancer --- p.19 / Chapter 2.2.4 --- Current Treatment for Advanced Cancer --- p.21 / Chapter 2.2.5 --- Limitation of Current Treatments --- p.24 / Chapter 2.3 --- Diagnosis and Treatment by TCM of Advanced Cancer --- p.26 / Chapter 2.3.1 --- (Advanced) Cancer from the TCM perspectives --- p.26 / Chapter 2.3.2 --- Diagnosis by TCM of Advanced Cancer --- p.27 / Chapter 2.3.3 --- Treatment by TCM of Advanced Cancer --- p.28 / Chapter 2.4 --- Current Evidences about the Clinical Effectiveness of TCM on Cancer Patients --- p.29 / Chapter 2.5 --- The concept of Health-related Quality of Life (HRQOL) --- p.35 / Chapter 2.5.1 --- The importance of HRQOL to cancer patients --- p.35 / Chapter 2.5.2 --- HRQOL instruments --- p.37 / Chapter 2.5.2.1 --- EORTC QLQ-C30 --- p.38 / Chapter 2.5.2.2 --- SF-36 --- p.39 / Chapter 2.6 --- Summary of Literature Review --- p.40 / Chapter 2.7 --- The research questions --- p.41 / Chapter 2.8 --- Research Hypotheses --- p.42 / Chapter 2.9 --- The design of TCM protocol --- p.42 / Chapter Chapter 3 --- Methodology --- p.45 / Chapter 3.1 --- Introduction --- p.45 / Chapter 3.2 --- Protocol --- p.45 / Chapter 3.2.1 --- Study Design --- p.46 / Chapter 3.2.2 --- Selection of Participants --- p.46 / Chapter 3.2.2.1 --- Inclusion criteria --- p.48 / Chapter 3.2.2.2 --- Exclusion criteria --- p.49 / Chapter 3.2.3 --- Sample size calculation --- p.50 / Chapter 3.2.4 --- Setting --- p.51 / Chapter 3.2.5 --- Interventions --- p.51 / Chapter 3.2.5.1 --- Treatment --- p.51 / Chapter 3.2.5.2 --- Medication and dose/dosage --- p.52 / Chapter 3.2.5.3 --- Treatment Assignment --- p.55 / Chapter 3.2.5.4 --- Concurrent Medications --- p.56 / Chapter 3.2.6 --- Procedure and Methods --- p.56 / Chapter 3.2.6.1 --- Informed Consent --- p.56 / Chapter 3.2.6.2 --- Documentation --- p.57 / Chapter 3.2.6.3 --- Assessment Procedure --- p.57 / Chapter 3.2.7 --- Outcome Measurements --- p.62 / Chapter 3.2.7.1 --- Survey Questionnaire --- p.62 / Chapter 3.2.7.2 --- Quality of life (QOL) instruments --- p.62 / Chapter 3.2.7.3 --- Global Ratings --- p.64 / Chapter 3.2.7.4 --- Physical Examination and Laboratory tests --- p.65 / Chapter 3.2.8 --- Safety Considerations --- p.66 / Chapter 3.2.8.1 --- Adverse Events (AE) --- p.66 / Chapter 3.2.8.2 --- Serious Adverse Event (SAE) --- p.66 / Chapter 3.2.8.3 --- Causality Assessment --- p.67 / Chapter 3.2.9 --- Ethical consideration --- p.68 / Chapter 3.2.10 --- Data Collection --- p.69 / Chapter 3.3 --- Data analysis --- p.69 / Chapter 3.4 --- Expected Outcomes of Study --- p.71 / Chapter Chapter 4 --- Results --- p.72 / Chapter 4.1 --- Study Progress --- p.72 / Chapter 4.2 --- The Participants --- p.72 / Chapter 4.3 --- Clinical characteristics and Socio-demographics of Participants --- p.75 / Chapter 4.4 --- Main Outcome - Quality of Life --- p.78 / Chapter 4.4.1 --- QLQ-C30 --- p.79 / Chapter 4.4.1.1 --- Scoring and Transforming of items into scales --- p.79 / Chapter 4.4.1.2 --- Changes of Individual Scale at Different Visits --- p.80 / Chapter 4.4.1.3 --- Clinical significance of Scales --- p.98 / Chapter 4.4.2 --- SF-36 --- p.104 / Chapter 4.4.2.1 --- Scoring and Transforming of items into scales --- p.104 / Chapter 4.4.2.2 --- Changes of Individual Scale at Different Visits --- p.104 / Chapter 4.4.2.3 --- SF-36 Summary Scales --- p.113 / Chapter 4.4.3 --- Correlation of QLQ-C30 and SF-36 --- p.115 / Chapter 4.5 --- Measurement of Physical examination --- p.117 / Chapter 4.5.1 --- Body Weight --- p.117 / Chapter 4.6 --- Measurement of Laboratory Blood tests --- p.118 / Chapter 4.6.1 --- "Comparison of CBC, RFT, LFT and LD" --- p.118 / Chapter 4.6.2 --- Tumor Markers --- p.120 / Chapter 4.7 --- Adverse Events and Serious Adverse Events --- p.121 / Chapter 4.8 --- Global Ratings --- p.123 / Chapter 4.8.1 --- Global Rating 1 - Severity of Disease --- p.123 / Chapter 4.8.2 --- Global Rating 2 - Global Disease Status --- p.124 / Chapter 4.8.2.1 --- Change in Global Disease Status --- p.125 / Chapter 4.8.2.2 --- Agreement between RCMP and clinician --- p.125 / Chapter 4.8.2.3 --- Patients' perception after treatment --- p.126 / Chapter 4.9 --- Distribution of TCM patterns and Chinese herbal medicines --- p.127 / Chapter 4.10 --- Survival Rate --- p.132 / Chapter 4.11 --- Conclusion --- p.133 / Chapter Chapter 5 --- Discussion --- p.135 / Chapter 5.1 --- Conclusion on findings --- p.135 / Chapter 5.2 --- Baseline profile of participants --- p.137 / Chapter 5.3 --- Feasibility of TCM on advanced cancer patients --- p.139 / Chapter 5.3.1 --- Recruitment of Participants --- p.139 / Chapter 5.3.2 --- Compliance of participants to the study schedule --- p.140 / Chapter 5.4 --- Health-related Quality of Life --- p.142 / Chapter 5.5 --- Safety of TCM --- p.149 / Chapter 5.6 --- Chinese medicine practitioner vs Western medicine doctor --- p.150 / Chapter 5.7 --- TCM pattern differentiation and treatment --- p.151 / Chapter 5.8 --- Implication of study --- p.154 / Chapter 5.8.1 --- Clinical implication --- p.154 / Chapter 5.8.2 --- Policy implication --- p.154 / Chapter 5.9 --- Limitations of the study --- p.155 / Chapter 5.10 --- Recommendations for further studies --- p.157 / Chapter 5.11 --- Overall Conclusion --- p.158 / Appendices --- p.160 / References --- p.177

Prostate cancer remains one of the most commonly diagnosed cancers in men and is a leading cause of cancer death. While great success has been achieved at curing early stage prostate cancer, limited success has been obtained when treating late-stage hormone independent prostate cancer. This is due to the increased propensity for skeletal and non-skeletal metastases. Thus development of novel effective therapeutic modalities against late stage prostate cancer is of critical importance. / Towards these objectives, I have focused my attention on the role of prostate secretory protein (PSP-94) which is expressed in normal individuals and in patients with early stage prostate cancer. Using our well established in vivo models of prostate cancer, I have evaluated the ability of PSP-94 and its amino acids 31-45 required (PCK3145) to decrease tumor growth and skeletal metastases in vivo and evaluated the potential mechanism(s) associated with PCK3145 anti-cancer actions. / Prostatic cancer can also develop as a result of epigenetic activation of tumor promoting genes. To evaluate the role of methylation in prostate cancer, late stage prostate cancer cells were treated with the universal methylating agent S-adenosylmethionine (SAM) and an anti-sense oligonucleotide directed against MBD2 (AS). Scrambled oligonucleotide was included as a control (S). Both SAM and MBD2-AS resulted in inhibition in uPA, MMP-2 and VEGF production leading to decreased tumor cell invasive capacity. However, SAM and MBD2-AS were not able to either further repress partially methylated genes (GSTP1) or reactivate already methylated genes (AR). Furthermore, SAM and MBD2-AS treatment resulted in significant reduction in tumor growth in vivo . Immunohistochemical and RT-PCR analyses carried out on SAM and MBD2-AS tumors revealed decreased protein and mRNA expression of uPA and MMP-2 which was partially due to increased methylation of the respective promoters even after 10 weeks post in vitro treatment as analyzed by bisulfate sequencing. In addition decreased levels of angiogenesis and tumor survival markers were observed. / Collectively, these studies are aimed at the development of novel reliable approached to diagnose and treat advanced, hormone refractory prostate cancer to reduce tumor associated morbidity and mortality.

Background. Both basal-like subtype and BRCA1-related breast cancers tend to have a poor overall prognosis and lack of effective treatments. Given that the lung cancer drug gefitinib and the leukemia drug dasatinib inhibit proteins also belonging to the molecular signature of this subtype, we and others hypothesized that they might be useful therapies for those two breast cancer subgroups. / Methods. Eight breast cancer cell lines were characterized by immunohistochemistry and western blotting and were treated with both drugs. Response was measured by using the sulphorhodamine B (SRB) assay. / Results. Two out of six basal-like cell lines were sensitive to gefitinib and five of six to dasatinib. BRCA1-related breast cancers were also responsive to dasatinib (three out of four). Moreover, EGFR and caveolin-1 act as markers for dasatinib sensitivity, but do not appear to be the primary targets of this drug. The presence of SRC but not ABL is necessary to achieve a response to dasatinib. / Conclusion. Dasatinib is more effective in the treatment of basal-like breast cancers than gefitinib and acts by inhibiting SRC and other molecules that are yet to be determined.

Bibliography: leaves 211-260 / xvii, 260 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1986

Prostate cancer is one of the leading causes of death in men aged 40-55. Genistein isoflavone (4', 5', 7-trihydroxyisoflavone) is a dietary phytochemical with demonstrated anti-tumor activities in a variety of cancers. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy drug, primarily used for secondary treatment of ovarian,cervical and small cell lung cancers. This study was to demonstrate the potential anticancer activities and synergy of topotecan-genistein combination in LNCaP prostate cancer cells. The potential efficacy and mechanism of topotecan/genistein-induced cell death was investigated... Results: The overall data indicated that i) both genistein and topotecan induce cellular death in LNCaP cells, ii) topotecan-genistein combination was significantly more efficacious in reducing LNCaP cell viabiligy compared to either genistein or topotecan alone, iii) in all cases, cell death was primarily through apoptosis, via the activation of the intrinsic pathway, iv) ROS levels were increased and VEGF expression was diminished significantly with the topotecan-genistein combination treatment, v) genetic analysis of topotecan-genistein treatment groups showed changes in genetic expression levels in pathway specific apoptotic genes.... Conclusion: Treatments involving topotecan-genistein combination may prove to be an attractive alternative phytotherapy of adjuvant therapy for prostate cancer. / by Vanessa P. Hèormann. / Thesis (Ph.D.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

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