Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment

Ena Wang, Scott Bussom, Jinguo Chen, Courtney Quinn, Davide Bedognetti, Wing Lam, Fulan Guan, Zaoli Jiang, Yichao Mark, Yingdong Zhao, David F. Stroncek, Jeffrey White, Francesco M. Marincola, Yung Chi Cheng

Research output: Contribution to journalArticle

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Abstract

Background -. Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906. Methods -. Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors. Results -. We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection. Conclusions -. PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.

Original languageEnglish
Article number38
JournalBMC Medical Genomics
Volume4
DOIs
Publication statusPublished - 2011
Externally publishedYes

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irinotecan
Tumor Microenvironment
Chinese Traditional Medicine
Neoplasms
Drug Therapy
Systems Biology
PHY 906
Complex Mixtures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment. / Wang, Ena; Bussom, Scott; Chen, Jinguo; Quinn, Courtney; Bedognetti, Davide; Lam, Wing; Guan, Fulan; Jiang, Zaoli; Mark, Yichao; Zhao, Yingdong; Stroncek, David F.; White, Jeffrey; Marincola, Francesco M.; Cheng, Yung Chi.

In: BMC Medical Genomics, Vol. 4, 38, 2011.

Research output: Contribution to journalArticle

Wang, E, Bussom, S, Chen, J, Quinn, C, Bedognetti, D, Lam, W, Guan, F, Jiang, Z, Mark, Y, Zhao, Y, Stroncek, DF, White, J, Marincola, FM & Cheng, YC 2011, 'Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment', BMC Medical Genomics, vol. 4, 38. https://doi.org/10.1186/1755-8794-4-38
Wang, Ena ; Bussom, Scott ; Chen, Jinguo ; Quinn, Courtney ; Bedognetti, Davide ; Lam, Wing ; Guan, Fulan ; Jiang, Zaoli ; Mark, Yichao ; Zhao, Yingdong ; Stroncek, David F. ; White, Jeffrey ; Marincola, Francesco M. ; Cheng, Yung Chi. / Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment. In: BMC Medical Genomics. 2011 ; Vol. 4.
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AU - Wang, Ena

AU - Bussom, Scott

AU - Chen, Jinguo

AU - Quinn, Courtney

AU - Bedognetti, Davide

AU - Lam, Wing

AU - Guan, Fulan

AU - Jiang, Zaoli

AU - Mark, Yichao

AU - Zhao, Yingdong

AU - Stroncek, David F.

AU - White, Jeffrey

AU - Marincola, Francesco M.

AU - Cheng, Yung Chi

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AB - Background -. Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906. Methods -. Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors. Results -. We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection. Conclusions -. PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.

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