Persistent anti-tumor effects via recombinant adeno-associated virus encoding herpes thymidine kinase gene monitored by PET-imaging

Kim, Ji Yun; Kim, Ji Hyun; Khim, Maria; Lee, Han Saem; Jung, Jin Hwa; Moon, Dae Hyuk; Jeong, Sunjoo; Lee, Heuiran

doi:10.3892/or.2011.1190

Cited by 8 publications

(5 citation statements)

References 18 publications

(18 reference statements)

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“…In particular, Romo1 is required for the oxidative stress induced by serum deprivation [48]. The release of mitochondrial ROS to cytosol depends on permeability of mitochondrial membrane as overexpression of Bcl-XL efficiently prevents both the Romo1-dependent ROS release and the serum-deprivation induced apoptosis [65]. As both p66shc and Romo1 participate in cytosolic release of mitochondrial ROS it would be important to test their possible functional cooperation during the induction of oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells

et al. 2014

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p66shc is a protein product of an mRNA isoform of SHC1 gene that has a pro-oxidant and pro-apoptotic activity and is implicated in the aging process. Mitochondria were suggested as a major source of the p66shc-mediated production of reactive oxygen species (ROS), although the underlying mechanisms are poorly understood. We studied effects of p66shc on oxidative stress induced by hydrogen peroxide or by serum deprivation in human colon carcinoma cell line RKO and in diploid human dermal fibroblasts (HDFs). An shRNA-mediated knockdown of p66shc suppressed and an overexpression of a recombinant p66shc stimulated the production of ROS in the both models. This effect was not detected in the mitochondrial DNA-depleted ρ0-RKO cells that do not have the mitochondrial electron transport chain (ETC). The p66shc-dependent accumulation of mitochondrial ROS was detected with HyPer-mito, a mitochondria-targeted fluorescent protein sensor for hydrogen peroxide. The fragmentation of mitochondria induced by mitochondrial ROS was significantly reduced in the p66shc deficient RKO cells. Mitochondria-targeted antioxidants SkQ1 and SkQR1 also decreased the oxidative stress induced by hydrogen peroxide or by serum deprivation. Together the data indicate that the p66shc-dependant ROS production during oxidative stress has mitochondrial origin in human normal and cancer cells.

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Section: Discussionmentioning

confidence: 99%

Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells

et al. 2014

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“…MCL1 contains serum response elements (SREs) in its promoter that may be activated in response to a variety of mitogenic and stress stimuli [ 41 ]. Both BCL-X L [ 42 , 43 ] and MCL-1 [ 44 , 45 ] have been also implicated in the cell response to serum starvation. It has been shown that MCL-1 and BCL-X L expression can be triggered by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3) in an erythroleukemic cell line [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

MCL-1, BCL-XL and MITF Are Diversely Employed in Adaptive Response of Melanoma Cells to Changes in Microenvironment

et al. 2015

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Melanoma cells can switch their phenotypes in response to microenvironmental insults. Heterogeneous melanoma populations characterized by long-term growth and a high self-renewal capacity can be obtained in vitro in EGF(+)bFGF(+) medium whilst invasive potential of melanoma cells is increased in serum-containing cultures. In the present study, we have shown that originally these patient-derived melanoma populations exhibit variable expression of pro-survival genes from the BCL-2 family and inhibitors of apoptosis (IAPs), and differ in the baseline MCL-1 transcript stability as well. While being transferred to serum-containing medium, melanoma cells are well protected from death. Immediate adaptive response of melanoma cells selectively involves a temporary MCL-1 increase, both at mRNA and protein levels, and BCL-XL can complement MCL-1, especially in MITFlow populations. Thus, the extent of MCL-1 and BCL-XL contributions seems to be cell context-dependent. An increase in MCL-1 level results from a transiently enhanced stability of its transcript, but not from altered protein turnover. Inhibition of MCL-1 preceding transfer to serum-containing medium caused the induction of cell death in a subset of melanoma cells, which confirms the involvement of MCL-1 in melanoma cell survival during the rapid alteration of growth conditions. Additionally, immediate response to serum involves the transient increase in MITF expression and inhibition of ERK-1/2 activity. Uncovering the mechanisms of adaptive response to rapid changes in microenvironment may extend our knowledge on melanoma biology, especially at the stage of dissemination.

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“…In a subsequent study, the same group confirmed these results and elaborated on the therapeutic mechanism of the HSV-TK system in MCF-7 cells [110]. AAV2-mediated delivery of sc39TK, a hyperactive variant of HSV-TK with enhanced affinity for GCV, to HeLa cells that were later implanted into mice to generate subcutaneous tumors enabled 70% tumor growth suppression upon GCV administration [111]. …”

Section: Aav Delivery Of Therapeutic Payloads In Preclinical Models Omentioning

confidence: 96%

Adeno-associated virus (AAV) vectors in cancer gene therapy

Santiago-Ortiz

Schaffer

2016

Journal of Controlled Release

154

131

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Gene delivery vectors based on adeno-associated virus (AAV) have been utilized in a large number of gene therapy clinical trials, which have demonstrated their strong safety profile and increasingly their therapeutic efficacy for treating monogenic diseases. For cancer applications, AAV vectors have been harnessed for delivery of an extensive repertoire of transgenes to preclinical models and, more recently, clinical trials involving certain cancers. This review describes the applications of AAV vectors to cancer models and presents developments in vector engineering and payload design aimed at tailoring AAV vectors for transduction and treatment of cancer cells. We also discuss the current status of AAV clinical development in oncology and future directions for AAV in this field.

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Persistent anti-tumor effects via recombinant adeno-associated virus encoding herpes thymidine kinase gene monitored by PET-imaging

Cited by 8 publications

References 18 publications

Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells

Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells

MCL-1, BCL-XL and MITF Are Diversely Employed in Adaptive Response of Melanoma Cells to Changes in Microenvironment

Adeno-associated virus (AAV) vectors in cancer gene therapy

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