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Molecular fingerprinting of radiation resistant tumors: can we apprehend and rehabilitate the suspects?

Rosser CJ, Gaar M, Porvasnik S - BMC Cancer (2009)

Bottom Line: Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors.Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2.In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, The University of Florida, Gainesville, Florida, 32610, USA. charles.rosser@urology.ufl.edu

ABSTRACT
Radiation therapy continues to be one of the more popular treatment options for localized prostate cancer. One major obstacle to radiation therapy is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors. Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer.

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Clonogenic assay of a panel of human prostate cancer cell lines subjected to irradiation. Utilizing clonogenic assay, gold standard for monitoring cell survival after irradiation, it was demonstrated that PC-3 cells that overexpressed Bcl-2 were the most radioresistant cells assayed.
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Figure 2: Clonogenic assay of a panel of human prostate cancer cell lines subjected to irradiation. Utilizing clonogenic assay, gold standard for monitoring cell survival after irradiation, it was demonstrated that PC-3 cells that overexpressed Bcl-2 were the most radioresistant cells assayed.

Mentions: In vitro, exposure of cancer cells to low, non-toxic doses of radiation resulted in the up regulation of Bcl-2, indicating these cells were attempting to adapt to the harmful environment. To confirm that Bcl-2 expression is associated with radiation resistance, human prostate cancer cells PC-3 were stably transfected to express Bcl-2 and subjected to 0–6 Gy radiation. The Bcl-2 expressing clone grew more colonies at higher doses of radiation than the control clones (Figure 2). Utilizing these same cell lines, our group down regulated Bcl-2 expression in this model and studied its effects with and without radiation in vitro and in vivo. Solely targeting Bcl-2 produced no cytotoxic effects and was associated with G1 cell cycle arrest. The combination of knock-down of Bcl-2 with irradiation sensitized the cells to the killing effects of radiation. In addition, both PC-3-Bcl-2 and PC-3-Neo xenografts in mice treated with the combination of targeting Bcl-2 and irradiation were >3 times smaller by volume than were xenografts in mice treated with either modality alone (Figure 3). The combination therapy was also associated with increased rates of apoptosis, decreased rates of angiogenesis, and decreased rates of proliferation [44].


Molecular fingerprinting of radiation resistant tumors: can we apprehend and rehabilitate the suspects?

Rosser CJ, Gaar M, Porvasnik S - BMC Cancer (2009)

Clonogenic assay of a panel of human prostate cancer cell lines subjected to irradiation. Utilizing clonogenic assay, gold standard for monitoring cell survival after irradiation, it was demonstrated that PC-3 cells that overexpressed Bcl-2 were the most radioresistant cells assayed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719662&req=5

Figure 2: Clonogenic assay of a panel of human prostate cancer cell lines subjected to irradiation. Utilizing clonogenic assay, gold standard for monitoring cell survival after irradiation, it was demonstrated that PC-3 cells that overexpressed Bcl-2 were the most radioresistant cells assayed.
Mentions: In vitro, exposure of cancer cells to low, non-toxic doses of radiation resulted in the up regulation of Bcl-2, indicating these cells were attempting to adapt to the harmful environment. To confirm that Bcl-2 expression is associated with radiation resistance, human prostate cancer cells PC-3 were stably transfected to express Bcl-2 and subjected to 0–6 Gy radiation. The Bcl-2 expressing clone grew more colonies at higher doses of radiation than the control clones (Figure 2). Utilizing these same cell lines, our group down regulated Bcl-2 expression in this model and studied its effects with and without radiation in vitro and in vivo. Solely targeting Bcl-2 produced no cytotoxic effects and was associated with G1 cell cycle arrest. The combination of knock-down of Bcl-2 with irradiation sensitized the cells to the killing effects of radiation. In addition, both PC-3-Bcl-2 and PC-3-Neo xenografts in mice treated with the combination of targeting Bcl-2 and irradiation were >3 times smaller by volume than were xenografts in mice treated with either modality alone (Figure 3). The combination therapy was also associated with increased rates of apoptosis, decreased rates of angiogenesis, and decreased rates of proliferation [44].

Bottom Line: Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors.Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2.In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, The University of Florida, Gainesville, Florida, 32610, USA. charles.rosser@urology.ufl.edu

ABSTRACT
Radiation therapy continues to be one of the more popular treatment options for localized prostate cancer. One major obstacle to radiation therapy is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Emerging evidence suggests that therapeutic agents targeting specific molecules might be combined with radiation therapy for more effective treatment of tumors. Recent studies suggest that modulation of these molecules by a variety of mechanisms (e.g., gene therapy, antisense oligonucleotides, small interfering RNA) may enhance the efficacy of radiation therapy by modifying the activity of key cell proliferation and survival pathways such as those controlled by Bcl-2, p53, Akt/PTEN and cyclooxygenase-2. In this article, we summarize the findings of recent investigations of radiosensitizing agents in the treatment of prostate cancer.

Show MeSH
Related in: MedlinePlus