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05 January 2018, Volume 3 Issue 1 Previous Issue    Next Issue
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Special Issue of Cancer Prevention and Treatment
News and comments: Do aristolochic acids truly increase the occurrence of hepatocellular carcinoma?
Editor Group of TMR, Xiong-Zhi Wu
1Traditional Medicine Research. 2018, 3 (1)  
Abstract ( 589 )     PDF (173KB) ( 251 )  

Recently, Science Translational Medicine pointed out that 78% of the 98 hepatocellular carcinoma (HCC) samples from Taiwan, China, showed distinctive signatures of aristolochic acids (AAs) exposure. In addition, 47% of the HCC samples from mainland China, 29% from Southeast Asia, 13% from Korea, and 2.7% from Japan showed AA signatures, which is much higher than those in North America and Europe, by searching for the AAs signature in 1,400 HCC samples from around the world. Researchers have suggested that there is a distinct relationship between AAs and HCC occurrence in Asia. As soon as the news comes out, the medical community is immediately triggered. Does AAs truly cause the occurrence of HCC?

AAs are not really just a compound and usually refer to several compounds from the aristolochiaceae plants that contain substituted phenanthrenes. There are over six hundreds of plants that contain AAs in the world, including sixty-five kinds of traditional Chinese medicine (TCM).

However, some experts in the industry have questioned the association between AAs and cancer. Firstly, are cancer-associated mutations caused by AAs themselves? The previous study failed to report when its patients began the treatment with AA-containing drugs and the amount of the administered dose. Secondly, this paper points out that AAs mutational signatures are mostly non-silent mutations in known oncogenic driver genes. However, HCC occurrences are caused by a variety of factors, and AAs-induced gene mutations may be only one such factor. Finally, if TCM is abused, heavy metal pollution of the TCM may be responsible for HCC occurrence, and therefore AAs would be related to the occurrence of HCC rather than have a direct causal relationship.

This special issue of cancer prevention and treatment will focus on the latest research on the effects of TCM in the prevention and treatment of cancer.

Modernization of Traditional Medicine
Nephrotoxicity and carcinogenesis of aristolochic acids and their derivates
Zi-Qi Jin, Jin-Wei Yuan, Jian Hao, Xiong-Zhi Wu
Traditional Medicine Research. 2018, 3 (1): 1-9.   https://doi.org/10.12032/TMR201809059
Abstract ( 1267 )   HTML ( 31 )     PDF (563KB) ( 512 )  

Highlights

This review summarized the toxicity and carcinogenesis of aristolochic acids and the underlying mechanisms.

Editor’s Summary

The mutational signature of aristolochic acids is related to the occurrence of HCC. However, the frequency of administration and dose, exposure time to aristolochic acids, and infectious situations of hepatitis B virus should also be further identified.

Abstract

Aristolochic acids (AAs), a natural mixture of 8-methoxy-6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAI) and 6-nitro-phenanthro-(3,4-d)-1,3-dioxolo-5-carboxylic acid (AAII), derived from aristolochiaceae species, has been reported to cause AAS-induced nephropathy and upper urothelial cancer. In this review, we summarize the information on the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis and oxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capability for renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGF-β-Smad signaling and promoting the migration of macrophages. Moreover, AAs-induced carcinogenesis may be due to the formation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes or proto-oncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAI metabolism.

TGF-β signaling in hepatocellular carcinoma suppression and progression
Jian Hao, Dan Chen
Traditional Medicine Research. 2018, 3 (1): 10-21.   https://doi.org/10.12032/TMR201809060
Abstract ( 1549 )   HTML ( 20 )     PDF (647KB) ( 626 )  

Highlights

This paper evaluates the suppressive and accelerant roles of TGF-β in hepatocellular carcinoma, discusses how a tumor-suppressor pathway can be so radically turned on its head and further provides some new molecular insights that may aid efforts towards targeted antitumor therapies.

Editor’s Summary

This review pays particular attention to the dual role of TGF-β in hepatocellular carcinoma. It also discusses the potential anti-tumor herbs through TGF-β signaling pathways.

Abstract

Derangements of several cell signaling pathways have been implicated in the initiation, progression, and development of hepatocellular carcinoma (HCC). One of such pathways is the activated TGF-β/Smad pathway. TGF-β inhibits proliferation and induces apoptosis in various cells types in the early tumor, and accumulation of loss-of-function mutations in the TGF-β receptor or Smad genes in tumor classify the pathway as a tumor suppressor. However, in chronic hepatitis, the cytostatic effect of TGF-β for hepatocytes attenuates as liver disease progresses from cirrhosis to HCC under persistent inflammatory microenvironments. In the later cancer period, TGF-β promotes tumor growth by modulating processes such as cell invasion, immune regulation, and microenvironment modification. Here we evaluate the suppressive and accelerant roles of TGF-β in HCC, discuss how a tumor-suppressor pathway can be so radically turned on its head and further provide some new molecular insights that may aid efforts towards targeted antitumor therapies. Moreover, we discussed the potential anti-tumor herbs through TGF-β signaling pathways.

Special Therapy of Traditional Medicine
Anti-angiogenesis effect of melittin on Mock/MHCC97-H cells by the regulation of cathepsin S in vivo
Guang-Qiang Ye, Zhi Zhang, Chun-Hui Ye, Keooudone Thammavong, Jing Xu
Traditional Medicine Research. 2018, 3 (1): 22-28.   https://doi.org/10.12032/TMR201809061
Abstract ( 713 )   HTML ( 15 )     PDF (557KB) ( 442 )  

Highlights

Melittin can inhibit the growth of tumors and angiogenesis by blocking the Cathepsin S-VEGF-A signaling pathway.

Editor’s Summary

The earliest literature recording on bee venom appeared in the book of Jishenlu, which published in Song Dynasty by Xu Xun (916 A.D. - 991 A.D.) and referenced the use of bee venom in the treatment of rheumatism.

Abstract

Objective: To study the anti-angiogenesis effect of melittin on human hepatoma Mock/MHCC97-H cells by regulating the expression of cathepsin S (CatS) in vivo. Methods: Models of in situ transplantation tumor of Mock/MHCC97-H cells and silencing cathepsin shRNA-CatS/ MHCC97-H cells in nude mice were established. The model mice were randomly divided into four groups. In the A1 group, the mice were inoculated with shRNA-CatS/MHCC97-H cells and treated with melittin. In the A2 group, the mice were inoculated with shRNA-CatS/MHCC97-H cells and treated with saline. In the B1 group, the mice were inoculated with Mock/MHCC97-H cells and treated with melittin. In the B2 group, the mice were inoculated with Mock/MHCC97-H cells and treated with saline. The A1 and B1 group were injected with melittin (80 mg/kg) intraperitoneally every day. The A2 and B2 group were injected with 0.2 mL normal saline intraperitoneally every day. After administration for 25 days, the animals were sacrificed. The tumor size and weight in nude mice in each group were recorded. The expression of CD34 protein in the xenograft tumor tissues was detected by immunohistochemistry. The expression of Cat S, VEGF-A, p-VEGFR2, Ras, Raf, p-Raf, MEK1, p-MEK1, ERK1/2 and p-ERK1/2 proteins were detected by western blot. Results: The B1 group had significantly smaller tumor volumes and lower tumor weights than the B2 group (both P < 0.001). There was no significant difference between the A1 group and A2 group in tumor volumes and weights. The number of CD34-positive microvessels in the B2 group was significantly higher than that in the A2 group (P < 0.001). The number of CD34-positive microvessels in the B1 group was significantly lesser than that in the A1 group (P < 0.001). Most strikingly, in the model featuring inoculation of Mock/MHCC97-H cells, CatS, VEGF-A, p-VEGFR2, Ras, Raf, p-Raf, MEK1, p-MEK1, ERK1/2 and p-ERK1/2 expression were inhibited when treated with melittin. However, in the model featuring the inoculation of shRNA-CatS/MHCC97-H cells, no such effects were observed with similar treatments. Conclusion: Melittin can inhibit the growth of tumors and angiogenesis by blocking the CatS-VEGf-A signaling pathway.

Empirical Formula Research
Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice
Ning-Ning Liu, Wan-Li Deng, Chao-Jun Wu, Yuan-Yuan Feng, Xin-Wen Ma, Qi Li
Traditional Medicine Research. 2018, 3 (1): 29-39.   https://doi.org/10.12032/TMR201809062
Abstract ( 1342 )   HTML ( 17 )     PDF (1342KB) ( 479 )  

Highlights

Jianpi Jiedu Recipe can reduce the infection rate of Helicobacter pylori in mice gastric mucosa by inhibiting the expression of MVD and VEGF, and reducing the inactivation of PTEN.

Editor’s Summary

In addition to use triple antibiotics to treat the infection of Helicobacter pylori, Jianpi Jiedu Recipe can reduce the infection rate of Helicobacter pylori and further prevent the occurrence of gastric cancer.

Abstract

Objective: To reveal the effect of Jianpi Jiedu recipe (JPJDR) on angiogenesis and the PTEN (Phosphatase and tensin homolog deleted on chromosome ten)/PI3K/AKT signaling pathway in the course of H. pylori infection-induced carcinogenesis of gastric mucosa in C57BL/6 mice. Methods: Two-hundred C57BL/6 mice were randomly divided into five groups (control group, model group, JPJDR low-dose group, JPJDR medium-dose group, and JPJDR high-dose group), 40 in each group. A mouse model of gastric cancer, induced by H. pylori standard strain infection, was established. The mice of JPJDR low-dose, middle-dose, and high-dose groups were intragastrically administered 250, 500, and 1000 mg/kg JPJDR per day, respectively. After 72 weeks, the H. pylori infection in gastric mucosa of the mice was analyzed by rapid urease test; the pathological changes in the gastric mucosa of mice were assessed by histopathological examination, and micro-vessel density (MVD), vascular endothelial growth factor (VEGF), and PTEN/PI3K/AKT levels were determined. Results: The incidence of gastric cancer in each group (control group, model group, JPJDR low-dose, medium-dose, high-dose group) was 0%, 26.3%, 13.2%, 10%, and 7.5% respectively. The incidence of gastric cancer in the Chinese medicine group was significantly lower than that of the model group (P = 0.020, P = 0.023, P = 0.007). The expression of MVD and VEGF in the model group was significantly higher than that in the control group (P = 0.002, P < 0.001), while the expression of MVD and VEGF decreased in the Chinese medicine group. The expression of p-PTEN and p-AKT in the model group was significantly higher than that in the control group (All P < 0.001), while Chinese medicine could reduce the expression of p-PTEN and p-AKT to varying extents. Conclusion: Long-term infection of C57BL/6 mice with H. pylori induces gastric carcinogenesis, by increasing gastric mucosal MVD, promoting the expression of VEGF, inhibiting the activity of PTEN, and activating the PI3K/AKT signaling pathway. JPJDR can reduce the infection rate of H. pylori in mouse gastric mucosa, inhibit the expression of MVD and VEGF, and reduce the inactivation of PTEN.

Gemcitabine and cisplatin combined with the Chinese herbal medicine compound Fuzhenggubenfang improve quality of life and progression-free survival in patients with advanced non-small cell lung cancer
Dong-Mei Jiang, Feng-Wei Wang, Li-Juan Zhang, Long Zhang, Tai Zhang, Wen-Hua Zhang
Traditional Medicine Research. 2018, 3 (1): 40-51.   https://doi.org/10.12032/TMR201809063
Abstract ( 1377 )   HTML ( 16 )     PDF (518KB) ( 398 )  

Highlights

Fuzhenggubenfang could be used as promising complementary medicine in chemotherapy for advanced NSCLC to improve quality of life and progression-free survival.

Editor’s Summary

Fuzhenggubenfang is the Chinese herbal medicine compound created on the basis of the addition and subtraction formula from Buzhongyiqi Soup, which was first recorded in Piweilun published in 1249 A.D. (Jin Dinasty of China).

Abstract

Objective: To assess the role of chemotherapy combined with the compound Chinese herbal medicine, Fuzhenggubenfang (FZGBF), for treating advanced non-small-cell lung cancer. Methods: A total of 84 eligible patients were enrolled from October 2013 to July 2016. Patients were randomized to receive either chemotherapy alone as the control group or chemotherapy combined with FZGBF as the experimental group. The primary endpoint of the study was quality of life (QOL) and progression-free survival (PFS). Secondary endpoints were tumor response rate, toxicity, dropout rate, and univariate and multivariate analyses of clinicopathologic factors for QOL and PFS. Results: There was a significant improvement in QOL, including better overall health (P < 0.001), physical function (P < 0.001), role function (P < 0.001), emotional function (P < 0.001), cognitive function (P < 0.001), and social function (P = 0.031). Less fatigue, nausea or vomiting, insomnia, appetite loss, constipation, and alopecia were noted (All P < 0.001) when FZGBF was combined with chemotherapy in comparison to chemotherapy alone. The experimental group had a better PFS compared with the control group (P = 0.032). There was no significant difference in tumor response rate. FZGBF significantly reduced chemotherapy-induced anemia (P < 0.001), neutropenia (P = 0.023), nausea and vomiting (P < 0.001). The use of Chinese herbal compounds had only mild side effects. In this study, factors influencing QOL were the use of the Chinese herbal compounds (P < 0.001), performance status score (P = 0.027), clinical staging of cancer (P = 0.009), and sex (P = 0.044). Use of traditional Chinese medicine (P = 0.043) and the number of previous chemotherapy sessions (P = 0.003) were the factors influencing PFS in this study. Conclusion: FZGBF could improve QOL, compliance to treatment, relieved chemotherapy-related toxicities of patients, and consequently improved PFS, which is a promising drug combination in complementary medicine for the treatment of advanced NSCLC.

Data mining analysis of Professor Liu Shangyi’s prescription characteristics in clinical medicine for the treatment of cancer patients with stomachache
Wen-Qi Huang, Zhu Yang, Dong-Xin Tang, Li Luo, Feng-Xi Long, Jing-Hui Wang, Bing Yang
Traditional Medicine Research. 2018, 3 (1): 52-61.   https://doi.org/10.12032/TMR201809064
Abstract ( 772 )   HTML ( 16 )     PDF (495KB) ( 452 )  

Highlights

The characteristics of Chinese medicine prescribed by Professor Liu Shangyi for the treatment of cancer patients with stomachache include the activation of blood circulation, removal of dampness, and alleviation of pain.

Editor’s Summary

The results of this study may provide guidance for the clinical treatment of cancer patients with stomachache.

Abstract

Objective: To analyze National Chinese Medicine Master Liu Shangyi’s prescription characteristics of clinical medicine for the treatment of cancer patients with stomachache. Methods: Data on prescriptions for cancer patients with stomachache between January 2014 and July 2016 were collected. The composing principles were analyzed by unsupervised data mining methods including Apriori algorithm in association rules and complex system entropy cluster. Results: Based on the analysis of 120 prescriptions, the frequency of each herb and association rules among the herbs were computed. Four core combinations and two new prescriptions were mined from the database. Compared to the before treatment, the clinical symptomatic grading of stomachache after treatment was lower (P < 0.001). Conclusion: Professor Liu has been successful in the treatment of cancer patients with stomachache by prescribing medication that aids in activating blood circulation, removing dampness, and alleviating pain.

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