PO-based Biodosimetry Evaluation Using an EPR Technique Acts As a Sensitive Index for Chemotherapy

Overview

Journal Oncol Lett

Specialty Oncology

Date 2018 Jul 17

PMID 30008915

Citations 1

Authors

Yuanjing Li

Shengxin Xu

Ming Cai

Affiliations

Soon will be listed here.

Abstract

The partial pressure of oxygen (PO) in the tumor microenvironment directly affects tumor sensitivity to chemotherapy. In the present study, a lithium phthalocyanine probe was implanted into MCF-7 human breast cancer cells, followed by transplant of the cells into nude mice. The present study used an electron paramagnetic resonance (EPR) oximetry measuring technique to dynamically monitor PO in the tumor microenvironment prior to and following chemotherapy, and aimed to determine the precise time window in which the microenvironmental PO peaked following chemotherapy. The results indicated that PO was significantly higher in breast cancer compared with control (P<0.05). Following four cycles of chemotherapy, the activity of NADH dehydrogenase, succinate-cytochrome reductase and cytochrome oxidase in the mitochondria of cells was significantly reduced when compared with their activity prior to chemotherapy (P<0.05). Regional blood flow in tumor tissues undergoing chemotherapy was significantly lower than that prior to chemotherapy (P<0.05). The rate of cellular apoptosis in the PO peak-based chemotherapy group was significantly greater than that in the conventional chemotherapy group after two and four cycles of chemotherapy (P<0.05). Tumor volume in the PO peak-based chemotherapy group was significantly reduced compared with that in the 0.9% NaCl solution control and the conventional chemotherapy groups after four cycles of chemotherapy (P<0.05). The tumor inhibitory rate of the experimental group was significantly higher than that of the conventional chemotherapy group (P<0.01). In conclusion, the present study may provide guidance for the development of effective strategies depending on tumor-maximal response to chemotherapy in an oxygen-rich environment. Additionally, the present study aimed to establish a foundation for a clinical noninvasive assessment intended to guide treatment and formulate individual regimens, in order to improve cancer therapeutics, sensitivity monitoring and curative effect estimation.

Citing Articles

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Rickard B, Overchuk M, Chappell V, Ruhi M, Sinawang P, Nguyen Hoang T Cancers (Basel). 2023; 15(9).

PMID: 37174030 PMC: 10177605. DOI: 10.3390/cancers15092564.

References

Strieth S, Eichhorn M, Sauer B, Schulze B, Teifel M, Michaelis U . Neovascular targeting chemotherapy: encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature. Int J Cancer. 2004; 110(1):117-24. DOI: 10.1002/ijc.20083. View

Topping G, Yung A, Schaffer P, Hoehr C, Kornelsen R, Kozlowski P . Manganese concentration mapping in the rat brain with MRI, PET, and autoradiography. Med Phys. 2017; 44(8):4056-4067. DOI: 10.1002/mp.12300. View

Menon C, Fraker D . Tumor oxygenation status as a prognostic marker. Cancer Lett. 2005; 221(2):225-35. DOI: 10.1016/j.canlet.2004.06.029. View

Carew J, Huang P . Mitochondrial defects in cancer. Mol Cancer. 2003; 1:9. PMC: 149412. DOI: 10.1186/1476-4598-1-9. View

Axelson H, Fredlund E, Ovenberger M, Landberg G, Pahlman S . Hypoxia-induced dedifferentiation of tumor cells--a mechanism behind heterogeneity and aggressiveness of solid tumors. Semin Cell Dev Biol. 2005; 16(4-5):554-63. DOI: 10.1016/j.semcdb.2005.03.007. View

Choi S, Oh J, Kim S . Ginsenoside Rh2 induces Bcl-2 family proteins-mediated apoptosis in vitro and in xenografts in vivo models. J Cell Biochem. 2010; 112(1):330-40. DOI: 10.1002/jcb.22932. View

Rak J, Yu J . Oncogenes and tumor angiogenesis: the question of vascular "supply" and vascular "demand". Semin Cancer Biol. 2004; 14(2):93-104. DOI: 10.1016/j.semcancer.2003.09.014. View

Sorensen M, Horsman M, Cumming P, Munk O, Keiding S . Effect of intratumoral heterogeneity in oxygenation status on FMISO PET, autoradiography, and electrode Po2 measurements in murine tumors. Int J Radiat Oncol Biol Phys. 2005; 62(3):854-61. DOI: 10.1016/j.ijrobp.2005.02.044. View

Orel V, Zabolotny M, Orel V . Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles. Med Hypotheses. 2017; 102:82-86. DOI: 10.1016/j.mehy.2017.03.006. View

10.

Vujaskovic Z, Rosen E, Blackwell K, Jones E, Brizel D, Prosnitz L . Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment. Int J Hyperthermia. 2003; 19(5):498-506. DOI: 10.1080/0265673031000121517. View

11.

Dunn J, Ding S, OHara J, Liu K, Rhodes E, Goda F . Can NMR diffusion-weighted imaging provide quantitative information on tumor interstital pO2?. Adv Exp Med Biol. 1997; 411:209-14. DOI: 10.1007/978-1-4615-5865-1_25. View

12.

Zhao X, He G, Chen Y, Pandian R, Kuppusamy P, Zweier J . Endothelium-derived nitric oxide regulates postischemic myocardial oxygenation and oxygen consumption by modulation of mitochondrial electron transport. Circulation. 2005; 111(22):2966-72. DOI: 10.1161/CIRCULATIONAHA.104.527226. View

13.

Erler J, Cawthorne C, Williams K, Koritzinsky M, Wouters B, Wilson C . Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol. 2004; 24(7):2875-89. PMC: 371100. DOI: 10.1128/MCB.24.7.2875-2889.2004. View

14.

Drozd E, Krzyszton-Russjan J, Marczewska J, Drozd J, Bubko I, Bielak M . Up-regulation of glutathione-related genes, enzyme activities and transport proteins in human cervical cancer cells treated with doxorubicin. Biomed Pharmacother. 2016; 83:397-406. DOI: 10.1016/j.biopha.2016.06.051. View

15.

Dong X, Xu P, Miao C, Fu Z, Li Q, Tang P . Hypoxia decreased chemosensitivity of breast cancer cell line MCF-7 to paclitaxel through cyclin B1. Biomed Pharmacother. 2012; 66(1):70-5. DOI: 10.1016/j.biopha.2011.11.016. View

16.

Cai M, Li Y, Xu Y, Swartz H, Chen C, Chen Y . Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning. Am J Physiol Heart Circ Physiol. 2011; 300(3):H1069-77. PMC: 3064316. DOI: 10.1152/ajpheart.00694.2010. View

17.

Keyes S, Heimbrook D, Fracasso P, Rockwell S, Sligar S, Sartorelli A . Chemotherapeutic attack of hypoxic tumor cells by the bioreductive alkylating agent mitomycin C. Adv Enzyme Regul. 1985; 23:291-307. DOI: 10.1016/0065-2571(85)90053-6. View

18.

Rudat V, Vanselow B, Wollensack P, Bettscheider C, Eble M, Dietz A . Repeatability and prognostic impact of the pretreatment pO(2) histography in patients with advanced head and neck cancer. Radiother Oncol. 2000; 57(1):31-7. DOI: 10.1016/s0167-8140(00)00200-0. View

19.

Khoshinani H, Afshar S, Najafi R . Hypoxia: A Double-Edged Sword in Cancer Therapy. Cancer Invest. 2016; 34(10):536-545. DOI: 10.1080/07357907.2016.1245317. View

20.

Stepanic V, cipak Gasparovic A, Gall Troselj K, Amic D, Zarkovic N . Selected attributes of polyphenols in targeting oxidative stress in cancer. Curr Top Med Chem. 2015; 15(5):496-509. DOI: 10.2174/1568026615666150209123100. View