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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

Response of tumors under different ZHENG conditions to herbal medicine treatments. (a) IHC staining for vimentin, a-SMA, and CD68 in tumors from the indicated group was performed for evaluating CAF proliferative activities and TAM infiltration, respectively. CAF proliferative activity and TAM infiltration were quantitatively evaluated as described in Figure 2(b). (b) The levels of SDF-1 and CCL5 in indicated tumors were evaluated with ELISA assay. Data are expressed as the mean ± SE. (c) IHC staining for CXCR4 and CCR5 on sections of indicated tumors. The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG was calculated. (d) Effect of herbal medicine on subcutaneously transplanted tumor with different ZHENG. The growth curves for each are shown. n.s.: not significant.
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fig4: Response of tumors under different ZHENG conditions to herbal medicine treatments. (a) IHC staining for vimentin, a-SMA, and CD68 in tumors from the indicated group was performed for evaluating CAF proliferative activities and TAM infiltration, respectively. CAF proliferative activity and TAM infiltration were quantitatively evaluated as described in Figure 2(b). (b) The levels of SDF-1 and CCL5 in indicated tumors were evaluated with ELISA assay. Data are expressed as the mean ± SE. (c) IHC staining for CXCR4 and CCR5 on sections of indicated tumors. The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG was calculated. (d) Effect of herbal medicine on subcutaneously transplanted tumor with different ZHENG. The growth curves for each are shown. n.s.: not significant.

Mentions: TCM usually means a comprehensive assessment of pathogenesis, location, and disease pathology, and the diagnosed ZHENG helps guide the application of Chinese herbal remedies. So, we used Huang lian jie du decoction (a traditional prescription used of treating Shi-Re ZHENG), Si jun zi decoction (a traditional prescription used of treating Pi-Xu ZHENG), and Tao hong si wu decoction (a traditional prescription used of treating Xue-Yu ZHENG) for Shi-Re, Pi-Xu, and Xue-Yu tumors, respectively. The herbal prescriptions used are shown in Table 1. We found that the herbal medicines had no or little effect on CAF proliferation or TAM infiltration (Figure 4(a)). We also evaluated the effects of the herbal medicines on SDF-1 secretion and CCL5 levels and found that the levels of which did not change after herbal medicine treatment (Figure 4(b)). Similarly, none of the herbal medicines had significant effects on CXCR4 or CCR5 expression in tumor cells (Figure 4(c)). These observations indicated that the herbal medicines had little effect on either the tumor or microenvironment. Finally we evaluated the effects of the herbal medicines on tumor growth and could not find any difference when the tumors were treated with different types of herbal medicine (Figure 4(d)). Therefore, our results suggest that a prescription based solely on ZHENG does not always result in a satisfactory response.


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)

Response of tumors under different ZHENG conditions to herbal medicine treatments. (a) IHC staining for vimentin, a-SMA, and CD68 in tumors from the indicated group was performed for evaluating CAF proliferative activities and TAM infiltration, respectively. CAF proliferative activity and TAM infiltration were quantitatively evaluated as described in Figure 2(b). (b) The levels of SDF-1 and CCL5 in indicated tumors were evaluated with ELISA assay. Data are expressed as the mean ± SE. (c) IHC staining for CXCR4 and CCR5 on sections of indicated tumors. The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG was calculated. (d) Effect of herbal medicine on subcutaneously transplanted tumor with different ZHENG. The growth curves for each are shown. n.s.: not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368347&req=5

fig4: Response of tumors under different ZHENG conditions to herbal medicine treatments. (a) IHC staining for vimentin, a-SMA, and CD68 in tumors from the indicated group was performed for evaluating CAF proliferative activities and TAM infiltration, respectively. CAF proliferative activity and TAM infiltration were quantitatively evaluated as described in Figure 2(b). (b) The levels of SDF-1 and CCL5 in indicated tumors were evaluated with ELISA assay. Data are expressed as the mean ± SE. (c) IHC staining for CXCR4 and CCR5 on sections of indicated tumors. The positive rates of CXCR4 and CCR5 protein in tumors with indicated ZHENG was calculated. (d) Effect of herbal medicine on subcutaneously transplanted tumor with different ZHENG. The growth curves for each are shown. n.s.: not significant.
Mentions: TCM usually means a comprehensive assessment of pathogenesis, location, and disease pathology, and the diagnosed ZHENG helps guide the application of Chinese herbal remedies. So, we used Huang lian jie du decoction (a traditional prescription used of treating Shi-Re ZHENG), Si jun zi decoction (a traditional prescription used of treating Pi-Xu ZHENG), and Tao hong si wu decoction (a traditional prescription used of treating Xue-Yu ZHENG) for Shi-Re, Pi-Xu, and Xue-Yu tumors, respectively. The herbal prescriptions used are shown in Table 1. We found that the herbal medicines had no or little effect on CAF proliferation or TAM infiltration (Figure 4(a)). We also evaluated the effects of the herbal medicines on SDF-1 secretion and CCL5 levels and found that the levels of which did not change after herbal medicine treatment (Figure 4(b)). Similarly, none of the herbal medicines had significant effects on CXCR4 or CCR5 expression in tumor cells (Figure 4(c)). These observations indicated that the herbal medicines had little effect on either the tumor or microenvironment. Finally we evaluated the effects of the herbal medicines on tumor growth and could not find any difference when the tumors were treated with different types of herbal medicine (Figure 4(d)). Therefore, our results suggest that a prescription based solely on ZHENG does not always result in a satisfactory response.

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