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Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine.

Chen Z, Chen LY, Wang P, Dai HY, Gao S, Wang K - Evid Based Complement Alternat Med (2012)

Bottom Line: In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG.We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5.The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

ABSTRACT
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus

Treatment response to herbal medicine involved with modification of tumor microenvironment. (a) The antitumor effect of Qingyihuaji formula (QYHJ) on tumor with different ZHENG. (b) The effect of QYHJ on CAF proliferative activities and TAM infiltration were evaluated as described in Figure 2. (c) The effect of QYHJ on secreted SDF-1 and CCL5 levels were evaluated as described in Figure 3(a). *P < 0.05; **P < 0.01.
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fig5: Treatment response to herbal medicine involved with modification of tumor microenvironment. (a) The antitumor effect of Qingyihuaji formula (QYHJ) on tumor with different ZHENG. (b) The effect of QYHJ on CAF proliferative activities and TAM infiltration were evaluated as described in Figure 2. (c) The effect of QYHJ on secreted SDF-1 and CCL5 levels were evaluated as described in Figure 3(a). *P < 0.05; **P < 0.01.

Mentions: Although tumors under different ZHENG conditions demonstrated differences in tumor microenvironment which may finally be reflected in tumor growth, the ZHENG conditions themselves seemed not to promote tumor growth. Thus, herbal medicines prescribed on the basis of the ZHENG condition alone did not affect tumor growth. To further understand the relatedness of tumor microenvironment, ZHENG, and the response to herbal treatment, we employed the Qingyihuaji formula (QYHJ), a prescription based on TCM theory whereby pancreatic cancer is considered to be of Shi-Re origin. QYHJ has been used to treat pancreatic cancer for many years [15, 16]. We first established mouse tumor models with the accompanying ZHENG conditions Shi-Re, Pi-Xu, and Xue-Yu. The mice were then treated with QYHJ and the tumor microenvironment and tumor growth were evaluated. We found that tumors of the different ZHENG condition models exhibited altered tumor microenvironments (Figures 5(b) and 5(c)), which is consistent with our previous observations (Figure 2). The QYHJ treatments altered the tumor microenvironments in the Shi-Re, Pi-Xu, Xue-Yu models dramatically, as demonstrated by decreased CAF proliferation and TAM infiltration (Figures 5(b) and 5(c)). Then when we correlated tumor microenvironment alteration with tumor growth, we surprisingly found that QYHJ treatment led to growth inhibition of tumors under different ZHENG conditions, although the inhibition rate varied among the different ZHENG (Figure 5(a)). This suggests that disease identification is sometime a requisite for the treatment of cancer with TCM. Taken together, these results indicate that a combination of disease diagnosis and ZHENG identification is essential for clinical TCM practice in cancer treatment. They also showed a relatedness between the tumor environment and ZHENG, and treatment response to herbal medicine involved the modification of the tumor microenvironment.


Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine.

Chen Z, Chen LY, Wang P, Dai HY, Gao S, Wang K - Evid Based Complement Alternat Med (2012)

Treatment response to herbal medicine involved with modification of tumor microenvironment. (a) The antitumor effect of Qingyihuaji formula (QYHJ) on tumor with different ZHENG. (b) The effect of QYHJ on CAF proliferative activities and TAM infiltration were evaluated as described in Figure 2. (c) The effect of QYHJ on secreted SDF-1 and CCL5 levels were evaluated as described in Figure 3(a). *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Treatment response to herbal medicine involved with modification of tumor microenvironment. (a) The antitumor effect of Qingyihuaji formula (QYHJ) on tumor with different ZHENG. (b) The effect of QYHJ on CAF proliferative activities and TAM infiltration were evaluated as described in Figure 2. (c) The effect of QYHJ on secreted SDF-1 and CCL5 levels were evaluated as described in Figure 3(a). *P < 0.05; **P < 0.01.
Mentions: Although tumors under different ZHENG conditions demonstrated differences in tumor microenvironment which may finally be reflected in tumor growth, the ZHENG conditions themselves seemed not to promote tumor growth. Thus, herbal medicines prescribed on the basis of the ZHENG condition alone did not affect tumor growth. To further understand the relatedness of tumor microenvironment, ZHENG, and the response to herbal treatment, we employed the Qingyihuaji formula (QYHJ), a prescription based on TCM theory whereby pancreatic cancer is considered to be of Shi-Re origin. QYHJ has been used to treat pancreatic cancer for many years [15, 16]. We first established mouse tumor models with the accompanying ZHENG conditions Shi-Re, Pi-Xu, and Xue-Yu. The mice were then treated with QYHJ and the tumor microenvironment and tumor growth were evaluated. We found that tumors of the different ZHENG condition models exhibited altered tumor microenvironments (Figures 5(b) and 5(c)), which is consistent with our previous observations (Figure 2). The QYHJ treatments altered the tumor microenvironments in the Shi-Re, Pi-Xu, Xue-Yu models dramatically, as demonstrated by decreased CAF proliferation and TAM infiltration (Figures 5(b) and 5(c)). Then when we correlated tumor microenvironment alteration with tumor growth, we surprisingly found that QYHJ treatment led to growth inhibition of tumors under different ZHENG conditions, although the inhibition rate varied among the different ZHENG (Figure 5(a)). This suggests that disease identification is sometime a requisite for the treatment of cancer with TCM. Taken together, these results indicate that a combination of disease diagnosis and ZHENG identification is essential for clinical TCM practice in cancer treatment. They also showed a relatedness between the tumor environment and ZHENG, and treatment response to herbal medicine involved the modification of the tumor microenvironment.

Bottom Line: In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG.We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5.The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

ABSTRACT
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus