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Antitumor Activity of a Combination of rAd2p53 Adenoviral Gene Therapy and Radiotherapy in Esophageal Carcinoma

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Abstract

The objective of this study was to determine if a combination of recombinant adenovirus 2 p53 (rAd2p53) gene therapy and radiotherapy would have significantly improved outcome from esophageal carcinoma when compared to radiotherapy (RT) alone. Forty-five patients diagnosed with esophageal carcinoma (confirmed squamous cell carcinoma) were randomly assigned to one of two study arms: treatment group: rAd2p53 gene therapy + RT (n = 22); and control group: radiotherapy (n = 23). For the treatment group, rAd2p53 was injected into multiple areas of the lesion once a week for 6 weeks avoiding deep ulcers points. RT was administered after 3 days of injection of rAd2p53. Patients in the control group only received radiotherapy. The overall response rate was significantly higher in the treatment group than in control group (P < 0.05). Furthermore, the complete response rate was 3 times higher in the treatment group than in the control group (P < 0.05). Transient fever and pain at injection site were the only side effects mentioned in the treatment group. In conclusion, this recombinant virus–RT combination is significantly more beneficial in palliation than RT alone, with minor side affects. However, its role as neoadjuvant therapy prior to surgical resection needs to be further investigated.

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References

  1. Yu, J. Y. W.-b., & Li, B.-S. (2007). Precision radiotherapy of cancer. Shandong Science and Technology Press, 3, 392–721.

    Google Scholar 

  2. Cooper, J. S., Guo, M. D., Herskovic, A., Macdonald, J. S., Martenson, J. A., Jr., Al-Sarraf, M., et al. (1999). Chemoradiotherapy of locally advanced esophageal cancer: Long-term follow-up of a prospective randomized trial (RTOG 85–01). Radiation Therapy Oncology Group. JAMA, 281, 1623–1627.

    Article  PubMed  CAS  Google Scholar 

  3. Koshy, M., Esiashvilli, N., Landry, J. C., Thomas, C. R., Jr., & Matthews, R. H. (2004). Multiple management modalities in esophageal cancer: Combined modality management approaches. Oncologist, 9, 147–159.

    Article  PubMed  Google Scholar 

  4. Swisher, S. G., Ajani, J. A., Komaki, R., Nesbitt, J. C., Correa, A. M., Cox, J. D., et al. (2003). Long-term outcome of phase II trial evaluating chemotherapy, chemoradiotherapy, and surgery for locoregionally advanced esophageal cancer. International Journal of Radiation Oncology, Biology, Physics, 57, 120–127.

    Article  PubMed  Google Scholar 

  5. Yin, W. (2006). Development of radiation treatment of esophageal cancer. Journal of Practical Oncology, 21, 99–103.

    Google Scholar 

  6. Cook, T., Wang, Z., Alber, S., Liu, K., Watkins, S. C., Vodovotz, Y., et al. (2004). Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Research, 64, 8015–8021.

    Article  PubMed  CAS  Google Scholar 

  7. Kunisaki, R., Ikawa, S., Maeda, T., Nakazaki, Y., Kurita, R., Harata, M., et al. (2006). p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate. The Journal of Gene Medicine, 8, 1121–1130.

    Article  PubMed  CAS  Google Scholar 

  8. Swisher, S. G., Roth, J. A., Komaki, R., Gu, J., Lee, J. J., Hicks, M., et al. (2003). Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clinical Cancer Research, 9, 93–101.

    PubMed  CAS  Google Scholar 

  9. Anderson, S. C., Johnson, D. E., Harris, M. P., Engler, H., Hancock, W., Huang, W. M., et al. (1998). p53 gene therapy in a rat model of hepatocellular carcinoma: Intra-arterial delivery of a recombinant adenovirus. Clinical Cancer Research, 4, 1649–1659.

    PubMed  CAS  Google Scholar 

  10. Hofseth, L. J., Hussain, S. P., & Harris, C. C. (2004). p53: 25 years after its discovery. Trends in Pharmacological Sciences, 25, 177–181.

    Article  PubMed  CAS  Google Scholar 

  11. Chen, C., Pan, J., & Xu, L. (2003). Recombinant adenovirus p53 agent injection combined with radiotherapy in treatment of nasopharyngeal carcinoma: A phase II clinical trial. Zhonghua Yi Xue Za Zhi, 83, 2033–2035.

    PubMed  CAS  Google Scholar 

  12. Yunqing, Z., & Li, X. (2002). The significance of the expression of P53 and p21 in esophageal cancer and nasopharyngeal cancer. Henan Journal of Oncology, 15, 287–288.

    Google Scholar 

  13. Tsuda, H., Sata, M., Ijuuin, H., Kumabe, T., Uchida, M., Ogou, Y., et al. (2002). A novel strategy for remission induction and maintenance in cancer therapy. Oncology Reports, 9, 65–68.

    PubMed  CAS  Google Scholar 

  14. Jain, P. T., & Gewirtz, D. A. (1999). Sustained enhancement of liposome-mediated gene delivery and gene expression in human breast tumour cells by ionizing radiation. International Journal of Radiation Biology, 75, 217–223.

    Article  PubMed  CAS  Google Scholar 

  15. Roth, J. A., Swisher, S. G., & Meyn, R. E. (1999). p53 tumor suppressor gene therapy for cancer. Oncology (Williston Park), 13, 148–154.

    CAS  Google Scholar 

  16. Shimada, H., Matsubara, H., & Ochiai, T. (2002). Gene therapy for esophageal cancer. Nippon Geka Gakkai Zasshi, 103, 371–375.

    PubMed  Google Scholar 

  17. Shimada, H., Shimizu, T., Ochiai, T., Liu, T. L., Sashiyama, H., Nakamura, A., et al. (2001). Preclinical study of adenoviral p53 gene therapy for esophageal cancer. Surgery Today, 31, 597–604.

    Article  PubMed  CAS  Google Scholar 

  18. Shimada, H., Matsubara, H., Shiratori, T., Shimizu, T., Miyazaki, S., Okazumi, S., et al. (2006). Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma. Cancer Science, 97, 554–561.

    Article  PubMed  CAS  Google Scholar 

  19. Lixin, Z., Limin, H., & Weizhen, Z. (2004). Synchronic radiotherapy-chemotherapy compared with radiotherapy alone in patients with upper and middle esophageal cancer. Tumor, 24, 303–304.

    Google Scholar 

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Acknowledgments

We thank Drs Lu Yao and Lei Tang for their guidance and support. We also thank Ms Bing for her excellent assistance in patient data analyses. This work was supported in part by Grant from the Ministry of Education, Culture, Sports, Science and Technology of China.

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Correspondence to Qingxia Fan.

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Lu, P., Yang, X., Huang, Y. et al. Antitumor Activity of a Combination of rAd2p53 Adenoviral Gene Therapy and Radiotherapy in Esophageal Carcinoma. Cell Biochem Biophys 59, 147–152 (2011). https://doi.org/10.1007/s12013-010-9122-z

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