Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer.

Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor's Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.

Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells.

The objective was to investigate the effect of activin A on matrix metalloproteinase 3 (MMP-3) production and to identify the role of activin A in chondroprotection. SW1353 cells, a human chondrosarcoma cell line, were stimulated with interleukin (IL) 1alpha and tumor necrosis factor (TNF) alpha, and the concentrations of activin A, follistatin, and MMP-3 secreted into the culture media were measured by enzyme-linked immunosorbent assay (ELISA). Activin A was added to cell cultures in the presence of IL-1alpha or TNFalpha to determine its effect on the production of MMP-3 and sulfated glycosaminoglycan (sGAG) (measured by Alcian blue assay). To study the mechanism responsible for the chondroprotective effects of activin A, the production of IL-1 receptor antagonist (IL-1ra) and tissue inhibitor for metalloproteinases 1 (TIMP-1) was examined by ELISA. Addition of IL-1alpha did not affect the production of activin A by cultured SW1353 cells. IL-1alpha and activin A inhibited the production of follistatin. Stimulation of SW1353 cells with activin A suppressed IL-1alpha-induced, but not TNFalpha-induced, MMP-3 expression. Activin A had no effect on the production of sGAG, IL-1ra, or TIMP-1, although it suppressed the induction of TIMP-1 and IL-1ra by IL-1alpha. This novel finding of MMP-3 inhibition by activin A suggests a new role of activin A in cartilage remodeling. Activin A may have therapeutic potential for preventing cartilage degradation.

Increased monocyte chemoattractant protein-1 in knee joints of rats with adjuvant-induced arthritis: in vivo microdialysis.

OBJECTIVE: Imbalance of inflammatory and antiinflammatory cytokines plays a critical role in the pathogenesis of rheumatoid arthritis (RA). Precise determination of these cytokines would lead to better understanding of the progression of RA. METHODS: We developed an in vivo microdialysis technique to directly monitor cytokine profiles in knee joints of rats with adjuvant-induced arthritis (AIA). Microdialysates drained from knee joints of rats with AIA and controls were collected and cytokine concentrations were measured by ELISA. Pathological changes of the knee joints and the source of monocyte chemoattractant factor-1 (MCP-1) secretion were also determined by histology and immunohistochemistry. RESULTS: MCP-1 expression in knee joints was significantly higher in AIA rats with erosive changes in their ankles than in normal rats, while interleukin 6 (IL-6) levels were similar in both cases. IL-1beta and interferon-gamma were not detectable in the microdialysates. Increased synovial proliferation and mononuclear inflammatory infiltrates were observed. Synovial cells and mononuclear inflammatory cells expressed both MCP-1 and its receptor, CCR2. CONCLUSION: Our results indicate that the in vivo microdialysis technique is capable of detecting cytokines in the knee joints of rats. Increased expression of MCP-1 and CCR2 in knee joints of AIA rats suggests a role for this cytokine in triggering the mechanisms involved in the pathogenesis of knee joint after ankle erosion.

Dual biological functions of an interleukin-1 receptor antagonist-interleukin-10 fusion protein and its suppressive effects on joint inflammation.

The aim of this study was to construct and purify a novel interleukin-1 receptor antagonist (IL-1ra)-interleukin-10 (IL-10) fusion protein and determine its biological function and anti-inflammatory effects. The isolated cDNAs of two inhibitory cytokines (IL-1ra, IL-10) were used to construct a cDNA for the IL-1ra-IL-10 fusion protein. The expressed recombinant cytokines and fusion product were purified and their biological properties analysed. The anti-IL-1 effect was evaluated by using a thymocyte-proliferation assay, and the IL-10 effect was investigated by the inhibition of interferon-gamma (IFN-gamma) production from splenocytes. The clinical response and histological analyses were studied in an adjuvant arthritic rat model. The fusion protein was 38 000 molecular weight in size. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting demonstrated that the purified protein was recognized by both IL-1ra and IL-10 antibodies. The fusion protein significantly inhibited IL-1-mediated thymocyte proliferation and concanavalin A (ConA)-primed IFN-gamma production from splenocytes. The fusion protein also suppressed joint swelling (paw circumference reduced from 5.0 +/- 0.2 to 4.1 +/- 0.1 cm; paw thickness approximately 2 mm in difference) and synovial inflammation in adjuvant arthritis of rats. Our investigations indicate that this fusion protein effectively suppresses inflammatory arthritis and may initiate a trend for future clinical application to target multiple molecules at the same time.