Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model

Ozawa, Tomoko; Hu, Jethro; Hu, Lanlin; Kong, Eileen L; Bollen, Andrew W.; Lamborn, Kathleen R.; Deen, Dennis F.

doi:10.1038/sj.cgt.7700814

Cited by 31 publications

(23 citation statements)

References 21 publications

(21 reference statements)

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“…It has been reported that during hypoxia, the proapoptotic protein Bax is translocated from the cytosol to the mitochondria, resulting in cytochrome c release and caspase activation [52]. More recently, this has been confirmed by other observations that designate HIF-1 induction as the basis of Bax upregulation [53].…”

Section: Hypoxia and Apoptosissupporting

confidence: 70%

Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions

et al. 2007

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LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Argue why hypoxic regions in solid tumors often contain viable cells that are intrinsically more resistant to treatment with radiotherapy or chemotherapy.2. Describe how exposure of cells or cell lines to hypoxic conditions has major implications on multiple intracellular pathways.3. Evaluate the importance of investigating chemoradiotherapy combinations in vitro under both normoxic and hypoxic conditions.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTAs it is now well established that human solid tumors frequently contain a substantial fraction of cells that are hypoxic, more and more in vitro research is focusing on the impact of hypoxia on the outcome of radiotherapy and chemotherapy. Indeed, the efficacy of irradiation and many cytotoxic drugs relies on an adequate oxygen supply. Consequently, hypoxic regions in solid tumors often contain viable cells that are intrinsically more resistant to treatment with radiotherapy or chemotherapy. Moreover, efforts have been made to exploit hypoxia as a potential difference between malignant and normal tissues. Nowadays, a body of evidence indicates that oxygen deficiency clearly influences some major intracellular pathways such as those involved in cell proliferation, cell cycle progression, apoptosis, cell adhesion, and others. Obviously, when investigating the effects of radiotherapy or chemotherapy or both combined under hypoxic conditions, it is essential to consider the influences of hypoxia itself on the cell. In this review, we first focus on the effects of hypoxia per se on some critical biological pathways. Next, we sketch an overview of preclinical and clinical research on radiotherapy, chemotherapy, and chemoradiation under hypoxic conditions. The Oncologist 2007;12: 690 -712

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Section: Hypoxia and Apoptosissupporting

confidence: 70%

Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions

et al. 2007

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“…One of the main proapoptotic proteins is BAX protein of bcl-2 family (2). Many researchers have shown that over expression of BAX gene can overcome anti-apoptotic proteins and cause cancer cells' apoptosis (3,4,31,32). In this study it was shown that BAX over expression can lead to apoptosis in cancer cells.…”

Section: Discussionmentioning

confidence: 72%

Hypoxia Response Elements Can Cause the Overexpression of the BAX mRNA Under Hypoxic Condition

2016

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Background: Suicide gene therapy is one of the modern methods of cancer treatment. However, transmission for tumor cells is one of the main challenges to overcome. Hypoxia is a common phenomenon in solid tumors that lead to changes in tumors microenvironment. Hypoxia-responsive element sequences are regulatory sequences that lead to activation of their upstream and downstream genes in hypoxic time. Bax is a strong proapoptotic gene that causes apoptosis in the time of over expression in cells. Objectives: The aim of this study is to use this sequence in order to specify suicide gene therapy by the help of a gene producing Bax protein under control of CMV promoter. Methods: The gene of BAX, BAX3HRE and 3HRE were cloned into interested vectors. In the next step, the function of HRE sequence on over expression of upstream gene under hypoxic condition was evaluated through western blot, MTT assay and real time PCR. Results: The results of this study indicate that cells transected by pcDNA3.1/BAX 3HRE. The rate of apoptosis in them significantly increased in comparison with pcDNA3.1/BAX in hypoxic conditions. Conclusions: Regarding the role of HREs in increasing the expression of its upstream genes, it can be used to specify suicide gene therapy in treatment of solid tumors.

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“…Tumor cells located in hypoxic tissue regions are resistant to both chemotherapy and radiotherapy and must be eradicated by alternative strategies [131]. Several genetic approaches have been validated in which HIF-1α-responsive promoters drive (i) production of toxic proteins or prodrug-converting enzymes such as the suicide genes bax [132], cytosine deaminase [133] or a Herpes simplex-derived thymidine kinase [134] or (ii) replication of oncolytic adenoviruses [135]. Gene delivery was accomplished either by conventional viral transduction (see below) or by anaerobic bacteria, which preferentially accumulate in hypoxic tumor tissues [136].…”

Section: Hypoxia-controlled Transgene Expressionmentioning

confidence: 99%

Pharmacologic transgene control systems for gene therapy

Weber

Fussenegger

2006

The Journal of Gene Medicine

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Pharmacologic transgene-expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine-tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high-precision trigger-inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals. Availability of a portfolio of compatible transcription control systems has enabled assembly of higher-order control circuitries providing simultaneous or independent control of several transgenes and the design of (semi-)synthetic gene networks, which emulate digital expression switches, regulatory transcription cascades, epigenetic expression imprinting, and cellular transcription memories. This review provides an overview of cutting-edge developments in transgene control systems, of the design of synthetic gene networks, and of the delivery of such systems for the prototype treatment of prominent human disease phenotypes.

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Functionality of hypoxia-induced BAX expression in a human glioblastoma xenograft model

Cited by 31 publications

References 21 publications

Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions

Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions

Hypoxia Response Elements Can Cause the Overexpression of the BAX mRNA Under Hypoxic Condition

Pharmacologic transgene control systems for gene therapy

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