Hypoxia is a common patho-physiological phenomenon in many types of diseases, including tumors, myocardial infarction and cerebral ischemia. It is believed that hypoxia not only affects the cellular regulation pathways, but also interferes genome, transcriptome and proteome inside tumor, eventually enhances tumor development by increasing malignancy and metastatic potential, induction of resistance towards radiotherapy and chemotherapy, activation of angiogenic mechanism, etc. One of the major biological events for hypoxia is induction of apoptosis, which is believed to provide a selective pressure for tumor progression. However, the mechanism of hypoxia induced apoptosis is not well established. In the present study, the molecular mechanism of hypoxia induced apoptosis was investigated and was found to be different in human squamous carcinoma A431 cells and human hepatocellular carcinoma HepG2 cells. In HepG2 cells, the conventional intrinsic apoptotic pathway that involved the activation of caspase-9 and -3 was found to be triggered by hypoxia through a newly identified p53 - Bnip-3 shunt. On the other hand, caspase-4 and -10 were found to be activated under hypoxia and may be related to hypoxia induced DNA fragmentation in A431 cells. Reoxygenation prior to hypoxia is the event after blood reperfusion in tumor vasculature. It is demonstrated in this study that reoxygenation is a distinctive stress from hypoxia, and it is very likely to be induced by reactive oxygen species. Apart from apoptosis, the mechanism for the development of drug resistance after hypoxia is also not yet clearly identified. In this study, resistance towards several common chemotherapeutic drugs after cells were subjected to hypoxia/reoxygenation cycles were demonstrated. Among them, the possible role of the genes related to methotrexate and cisplatin resistance were also investigated. / Ho Yiu Fung. / "August 2006." / Adviser: Tim-Tak Kwok. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1393. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 159-176). / 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.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343911 |
| Date | January 2006 |
| Contributors | Ho, Yiu Fung., Chinese University of Hong Kong Graduate School. Division of Biochemistry. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xv, 176 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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