Advanced but Not Localized Prostate Cancer is Associated With Increased Oxidative Stress

Yossepowitch, Ofer; Pinchuk, Ilya; Gur, Uri; Neumann, Avivit; Lichtenberg, Dov; Baniel, Jack

doi:10.1016/j.juro.2007.05.145

Cited by 46 publications

(36 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to melanin biosynthesis, melanoma cells contain particularly high levels of ROS (Wittgen & van Kempen 2007), and this may result in this cancer being sensitive to elesclomol-induced cytotoxicity. Advanced prostate cancer is also associated with a state of high oxidative stress (Yossepowitch et al 2007), suggesting that the prostate cancer cell lines used in this study would be similarly sensitive to elesclomol. A phase I/II study of elesclomol plus docetaxel in patients with metastatic castration refractory prostate cancer has recently been completed (NCT00808418), although the findings are currently unknown.…”

Section: Discussionmentioning

confidence: 93%

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Rae

Mairs

2016

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. Materials and methods: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with X-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids. Results: Inhibitors of the PARP DNA repair pathway, olaparib and rucaparib, and the HSP90 inhibitor 17-DMAG, enhanced the clonogenic cell kill and spheroid growth delay induced by X-radiation. However, the oxidative stress-inducing drug elesclomol failed to potentiate the effects of X-radiation. PARP inhibitors arrested cells in the G 2 /M phase when administered as single agents or in combination with radiation, whereas elesclomol and 17-DMAG did not affect radiation-induced cell cycle modulation. Conclusion: These results indicate that radiotherapy of prostate cancer may be optimized by combination with inhibitors of PARP or HSP90, but not elesclomol. ARTICLE HISTORY

show abstract

Section: Discussionmentioning

confidence: 93%

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Rae

Mairs

2016

International Journal of Radiation Biology

View full text Add to dashboard Cite

show abstract

“…Moreover, high levels of oxidative stress have been documented in cancer cells and human cancer tissues, including from PCA (12,(27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

A Novel Experimental Heme Oxygenase-1–Targeted Therapy for Hormone-Refractory Prostate Cancer

Alaoui‐Jamali

Bismar

Gupta³

et al. 2009

Cancer Research

119

View full text Add to dashboard Cite

Heme oxygenase-1 (HO-1), a member of the heat shock protein family, plays a key role as a sensor and regulator of oxidative stress. Herein, we identify HO-1 as a biomarker and potential therapeutic target for advanced prostate cancer (PCA). Immunohistochemical analysis of prostate tissue using a progression tissue microarray from patients with localized PCA and across several stages of disease progression revealed a significant elevation of HO-1 expression in cancer epithelial cells, but not in surrounding stromal cells, from hormonerefractory PCA (HRPCA) compared with hormone-responsive PCA and benign tissue. Silencing the ho-1 gene in HRPCA cells decreased the HO-1 activity, oxidative stress, and activation of the mitogen-activated protein kinase-extracellular signalregulated kinase/p38 kinase. This coincided with reduced cell proliferation, cell survival, and cell invasion in vitro, as well as inhibition of prostate tumor growth and lymph node and lung metastases in vivo. The effect of ho-1 silencing on these oncogenic features was mimicked by exposure of cells to a novel selective small-molecule HO-1 inhibitor referred to as OB-24. OB-24 selectively inhibited HO-1 activity in PCA cells, which correlated with a reduction of protein carbonylation and reactive oxygen species formation. Moreover, OB-24 significantly inhibited cell proliferation in vitro and tumor growth and lymph node/lung metastases in vivo. A potent synergistic activity was observed when OB-24 was combined with Taxol. Together, these results establish HO-1 as a potential therapeutic target for advanced PCA. [Cancer Res 2009;69(20):8017-24]

show abstract

“…[15][16][17] Both the tumour growth and progression and the systemic inflammatory response have the potential to produce free radicals and thus increase oxidative stress. Indeed, both the presence and progression of cancer [18][19][20][21] and the systemic inflammatory response [22][23][24][25] are associated with lower carotenoid concentrations. However, to date the majority of studies have only included relatively small number of cancer patients ( 30).…”

mentioning

confidence: 99%

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Leung

Crozier

Talwar

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Both the tumour growth and progression and the systemic inflammatory response have the potential to increase oxidative stress. We therefore examined the relationship between lipid-soluble antioxidant vitamins, lipid peroxidation, the systemic inflammatory response and survival in patients with primary operable (n 5 53) and advanced inoperable (n 5 53) colorectal cancer. Compared with those patients with primary operable colorectal cancer, patients with unresectable liver disease had significantly lower median concentrations of a-tocopherol (p < 0.001), lutein (p < 0.001), lycopene (p < 0.001), a-carotene (p < 0.01) and b-carotene (p < 0.001) and higher malondialdehyde concentrations. An elevated systemic inflammatory response (Glasgow prognostic score, mGPS) was associated with a greater proportion of females (p < 0.05) and more advanced tumour stage (p < 0.05), lower circulating levels of retinol (p < 0.01), lutein (p < 0.01), lycopene (p < 0.01) and a-(p < 0.01) and b-carotene but not MDA (p 5 0.633). In the liver metastases group 41 patients died of their cancer and a further 1 patient died of intercurrent disease on follow-up. On univariate survival analysis, mGPS (p < 0.01), retinol (p < 0.001), atocopherol (p < 0.05) and a-carotene (p < 0.05) were associated significantly with cancer-specific survival. On multivariate survival analysis of these significant variables, only mGPS (p < 0.01) and retinol (p < 0.001) were independently associated with cancer-specific survival. The results of the present study showed that the systemic inflammatory response was associated with a reduction of lipid-soluble antioxidant vitamins, whereas advanced tumour stage was associated with increased lipid peroxidation in patients with colorectal cancer. Of the antioxidant vitamins measured, only retinol was independently associated with cancer-specific survival. ' 2008 Wiley-Liss, Inc.Key words: colorectal cancer; vitamin A; vitamin E; carotenoids; malonyldialdehyde; TNM stage; Glasgow prognostic score; survival Colorectal cancer remains the second commonest cause of cancer deaths in Western Europe and North America. Each year in the United Kingdom, there are 35,000 new cases and 16,000 deaths attributable to the disease.1 Overall survival is poor; even in those patients who undergo potentially curative resection, more than one-third die within 5 years. It is increasingly recognised that variations in outcome in cancer patients are not solely determined by the characteristics of the tumour but also by host-immune response factors. [3][4][5] It is now accepted that the host systemic inflammatory response can be assessed by examining the changes in the circulating concentrations of acute-phase proteins, such as an elevated concentration of C-reactive protein and a low concentrations of albumin 6 and that these have prognostic values in patients with cancer. 7,8 Recently, the combination of C-reactive protein and albumin, known as the Glasgow prognostic score (GPS), has been validated as a prognostic factor in patients with color...

show abstract

Advanced but Not Localized Prostate Cancer is Associated With Increased Oxidative Stress

Abstract: Patients with advanced prostate cancer are subject to high oxidative stress, as determined by increased susceptibility of serum lipids to peroxidation. This association was not detected in patients with localized cancer and it is not attributable to altered levels of alpha-tocopherol.

Cited by 46 publications

References 17 publications

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

A Novel Experimental Heme Oxygenase-1–Targeted Therapy for Hormone-Refractory Prostate Cancer

Vitamin antioxidants, lipid peroxidation, tumour stage, the systemic inflammatory response and survival in patients with colorectal cancer

Contact Info

Product

Resources

About