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Xu Y, Zhang YX, Chen HY, Chang LS, Gou XJ, Chen WL. Integrating Network Pharmacology and In vivo Experimental Validation to Reveal the Mechanism of FuZheng YiLiu Formula on Estrogen Receptor Positive Breast Cancer. Comb Chem High Throughput Screen 2025; 28:49-63. [PMID: 37957900 DOI: 10.2174/0113862073255044231027061742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 08/04/2023] [Accepted: 09/14/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND AND PURPOSE FuZheng YiLiu Formula (FZYL) is a commonly used formula for postoperative estrogen receptor-positive (ER+) breast cancer and post-radiotherapy deficiency of both Qi and Yin. FZYL has been used in clinical practice for decades because of its ability to effectively improve the symptoms of deficiency in cancer patients. However, its mechanism needs to be further clarified. In this paper, we will observe the effect of FZYL on mice with ER+ breast cancer and explore the mechanism by which it improves the symptoms of ER+ breast cancer. MATERIALS AND METHODS A tumor xenograft mouse model was established to detect tumor growth in vivo in order to evaluate the pharmacological effects of FZYL on ER+ breast cancer. The main targets of FZYL were identified by extracting the FZYL components and the corresponding potential target genes of breast cancer from the established database and constructing a proteinprotein interaction network of shared genes using the string database. GO functional annotation and KEGG pathway enrichment analysis were performed, and molecular docking, molecular dynamics simulations, western blotting analysis, and RT-qPCR were performed to confirm the validity of targets in the relevant pathways. RESULTS FZYL was able to significantly reduce the size of tumors in vivo and had a significant therapeutic effect on tumor xenograft mice. GO and KEGG pathway enrichment analyses indicated that the effects of FZYL may be mediated by oxidative stress levels, apoptotic signaling pathways, and cell cycle proliferation. By RT-qPCR and protein blotting assays, FZYL targeted the key targets of TP53, JUN, ESR1, RELA, MYC, and MAPK1 to exert its effects. The key active components of FZYL are quercetin, luteolin, stigmasterol, and glycitein. Molecular docking and molecular dynamics simulation results further demonstrated that the key active components of FZYL are stably bound to the core targets. CONCLUSION In this study, the potential active ingredients, potential core targets, key biological pathways, and signaling pathways involved in the treatment of breast cancer with FZYL were identified, providing a theoretical basis for further anti ER+ breast cancer research.
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Affiliation(s)
- Yuan Xu
- School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
| | - Ying-Xuan Zhang
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
| | - Hong-Yu Chen
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
| | - Li-Sheng Chang
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
| | - Xiao-Jun Gou
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
| | - Wen-Li Chen
- Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai 201999, China
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Lin SK, Lai JN. Enhancing Traditional Chinese Medicine healthcare system in Taiwan post-COVID-19 pandemic: A strategic focus on specialization. J Formos Med Assoc 2024; 123 Suppl 3:S207-S214. [PMID: 39307619 DOI: 10.1016/j.jfma.2024.09.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 08/20/2024] [Accepted: 09/10/2024] [Indexed: 11/08/2024] Open
Abstract
Despite the advancements in precision medicine, regenerative medicine, and smart healthcare, traditional Chinese medicine (TCM) remains vital in Taiwan, reflecting its cultural and historical heritage. TCM is commonly used in conjunction with or as an alternative to conventional medicine and is reimbursed by Taiwan's National Health Insurance, enabling the Taiwanese people to integrate traditional and modern treatments for comprehensive healthcare. This article explores the critical role of specialization in TCM amid evolving healthcare challenges. This highlights the need for specialized knowledge among TCM physicians to manage iatrogenic risks, such as drug-herb interactions, and to improve healthcare outcomes, particularly when integrating TCM with Western medicine. Specialization enhances treatment precision, patient outcomes, and clinical research quality. Drawing on South Korea's experience in establishing a specialist physician system for traditional Korean medicine, Taiwan's Ministry of Health and Welfare's initiatives to advance systematic TCM training and regulatory frameworks were examined, showcasing the development and implementation of a TCM specialist physician training program. In conclusion, specialized physician training in TCM improves patient care, optimizes healthcare utilization, and promotes long-term sustainability of the health insurance system by aligning TCM practices with modern healthcare needs.
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Affiliation(s)
- Shun-Ku Lin
- Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, 112, Taiwan; Department of Chinese Medicine, Taipei City Hospital, Renai Branch, Taipei City, 106, Taiwan; General Education Center, University of Taipei, Taipei City, 111, Taiwan; The Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei City, 112, Taiwan
| | - Jung-Nien Lai
- The Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei City, 112, Taiwan.
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Hou YN, Chimonas S, Patel P, Kantor ED, Traina TA, Yen HR, Mao JJ. Traditional Chinese Medicine Herbs for Breast Cancer Prevention and Survival: A Narrative Review of Epidemiological Studies from Taiwan. Curr Oncol Rep 2024; 26:1321-1333. [PMID: 39361077 DOI: 10.1007/s11912-024-01595-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE OF REVIEW This review aims to describe the association of integrating traditional Chinese medicine (TCM) herbs into conventional medicine (CM) in preventing breast cancer and improving survival rates among breast cancer patients of Taiwan. RECENT FINDINGS Of 7 relevant studies, spanning 2014-2023, 4 investigated breast cancer risk in women with menopausal symptoms and other comorbidities. All 4 reported that TCM herbal use was associated with lower risks of developing breast cancer. Three studies investigated survival in newly-diagnosed breast cancer patients receiving CM. All reported that adjunctive TCM users had lower mortality rates than CM-only patients. However, the heterogeneity of study designs, populations, and interventions may limit the generalizability and robustness of the findings. TCM herbs may promote breast cancer prevention and survival when used alongside CM. More rigorous observational research and clinical trials in specific patient populations are needed to guide clinical decision-making.
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Affiliation(s)
- Yen-Nien Hou
- Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, 321 East 61st Street, 4th Floor, New York, NY, 10065, USA
| | - Susan Chimonas
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, Cancer Center, New York, NY, USA
| | - Prusha Patel
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, Cancer Center, New York, NY, USA
| | - Elizabeth D Kantor
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, Cancer Center, New York, NY, USA
| | - Tiffany A Traina
- Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA
| | - Hung-Rong Yen
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Division of Integration of Chinese and Western Medicine, Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jun J Mao
- Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, 321 East 61st Street, 4th Floor, New York, NY, 10065, USA.
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Wang YK, Zhu RW, Gao ZP, Tao Y. Quality of life and survival analyses of breast cancer cases treated with integrated traditional Chinese and Western medicine. World J Clin Cases 2024; 12:4074-4081. [PMID: 39015919 PMCID: PMC11235521 DOI: 10.12998/wjcc.v12.i20.4074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Breast cancer (BC) is the second leading cause of tumor-related mortality after lung cancer. Chemotherapy resistance remains a major challenge to progress in BC treatment, warranting further exploration of feasible and effective alternative therapies. AIM To analyzed the quality of life (QoL) and survival of patients with BC treated with integrated traditional Chinese and Western medicine (TCM-WM). METHODS This study included 226 patients with BC admitted to the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine between February 2018 and February 2023, including 100 who received conventional Western medicine treatment (control group) and 126 who received TCM-WM treatment (research group). The total effective rate, side effects (alopecia, nausea and vomiting, hepatorenal toxicity, and myelosuppression), QoL assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 1-year overall survival (OS), recurrence and metastasis rates, and serum inflammatory factors [interleukin (IL)-6, IL-10, and tumor necrosis factor alpha] were comparatively analyzed. RESULTS The research group showed statistically better overall efficacy, EORTC QoL-C30 scores, and 1-year OS than the control group, with markedly lower side effects and 1-year recurrence and metastasis rates. Moreover, the posttreatment levels of serum inflammatory in the research group were significantly lower than the baseline and those in the control group. CONCLUSION Overall, TCM-WM demonstrated significantly improved therapeutic efficacy while ensuring drug safety in BC, which not only improved patients' QoL and prolonged survival, but also significantly inhibited the inflammatory response.
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Affiliation(s)
- Yu-Kun Wang
- Thyroid and Breast Surgery Department, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Rong-Wei Zhu
- Clinical Integration of Traditional Chinese and Western Medicine, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Peng Gao
- Clinical Integration of Traditional Chinese and Western Medicine, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
| | - Yi Tao
- Clinical Integration of Traditional Chinese and Western Medicine, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
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Wang KH, Shen HS, Chu SC, Wang TF, Lin CW, Huang WH, Wu YF, Ho CC, Pang CY, Li CC. Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial. JMIR Res Protoc 2024; 13:e55662. [PMID: 38466979 DOI: 10.2196/55662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/25/2024] [Accepted: 02/01/2024] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/55662.
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Affiliation(s)
- Kai-Hung Wang
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Hsuan-Shu Shen
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Sports Medicine Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Sung-Chao Chu
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Tso-Fu Wang
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Ching-Wei Lin
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Wei-Han Huang
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Department of Clinical Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Yi-Feng Wu
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Ching-Chun Ho
- Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Cheng-Yoong Pang
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Chi-Cheng Li
- Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- School of Medicine, Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Center of Stem Cell and Precision Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
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Xie J, Huang H, Li X, Ouyang L, Wang L, Liu D, Wei X, Tan P, Tu P, Hu Z. The Role of Traditional Chinese Medicine in Cancer Immunotherapy: Current Status and Future Directions. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2023; 51:1627-1651. [PMID: 37638827 DOI: 10.1142/s0192415x2350074x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
The tumor microenvironment (TME) plays an important role in the development of tumors. Immunoregulatory cells and cytokines facilitate cancer cells to avoid immune surveillance. Overexpression of immune checkpoint molecules such as CTLA-4 and PD-1/PD-L1 inhibits immune function and enables cancer cells to avoid clearance by the immune system. Thus, minimizing tumor immunosuppression could be an important strategy for cancer therapy. Currently, many immune checkpoint-targeted drugs, such as PD-1/PD-L1 inhibitors, have been approved for marketing and have shown unique advantages in the clinical treatment of cancers. The concept of "strengthening resistance to eliminate pathogenic factors" in traditional Chinese medicine (TCM) is consistent with the immunotherapy of cancer. According to previous studies, the role of TCM in tumor immunotherapy is mainly associated with the positive regulation of natural killer cells, CD8/CD4 T cells, dendritic cells, M2 macrophages, interleukin-2, tumor necrosis factor-[Formula: see text], and IFN-[Formula: see text], as well as with the negative regulation of Tregs, myeloid-derived suppressor cells, cancer-associated fibroblasts, PD-1/PD-L1, transforming growth factor-[Formula: see text], and tumor necrosis factor-[Formula: see text]. This paper summarizes the current research on the effect of TCM targeting the TME, and further introduces the research progress on studying the effects of TCM on immune checkpoints. Modern pharmacological studies have demonstrated that TCM can directly or indirectly affect the TME by inhibiting the overexpression of immune checkpoint molecules and enhancing the efficacy of tumor immunotherapy. TCM with immunomodulatory stimulation could be the key factor to achieve benefits from immunotherapy for patients with non-inflammatory, or "cold", tumors.
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Affiliation(s)
- Jinxin Xie
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Huiming Huang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Xingxing Li
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, P. R. China
| | - Lishan Ouyang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Longyan Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Dongxiao Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Xuejiao Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Peng Tan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Pengfei Tu
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
| | - Zhongdong Hu
- Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, P. R. China
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Li TF, Hwang IH, Tsai CH, Hwang SJ, Wu TP, Chen FP. To explore the effects of herbal medicine among cancer patients in Taiwan: A cohort study. J Chin Med Assoc 2023; 86:767-774. [PMID: 37273198 DOI: 10.1097/jcma.0000000000000945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer. METHODS This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers). RESULTS We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05). CONCLUSION Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk.
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Affiliation(s)
- Tsai-Feng Li
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - I-Hsuan Hwang
- Center for Quality Control, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Hung Tsai
- Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shinn-Jang Hwang
- Family Medicine Division, En Chu Kong Hospital, New Taipei, Taiwan, ROC
| | - Ta-Peng Wu
- Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fang-Pey Chen
- Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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Chen KW, Chung KP, Hsu CH. The intention of utilization and experience toward traditional Chinese medicine among breast cancer patients in the early and late stages: a qualitative study. BMC Complement Med Ther 2023; 23:226. [PMID: 37420247 DOI: 10.1186/s12906-023-04054-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/24/2023] [Indexed: 07/09/2023] Open
Abstract
BACKGROUND In Taiwan, breast cancer patients usually take conventional medicine and traditional Chinese medicine simultaneously. The utilization of traditional Chinese medicine among breast cancer patients at various stages has not been examined. This study aims to compare the intention of utilization and experience toward traditional Chinese medicine among early- and late-stage breast cancer patients. METHOD This qualitative research collected data from breast cancer patients through focus groups interview by convenience sampling. Conducted in 2 branches of Taipei City Hospital, a public hospital managed by the Taipei City government. Breast cancer patients > 20 years old and had used TCM for breast cancer therapy for at least 3 months were included in the interview. A semi-structured interview guide was adopted in each focus group interview. In the following data analysis, stages I and II were considered early-stage, and stages III and IV were late-stage. For analyzing the data and reporting the results, we used qualitative content analysis as the approach for data analysis, assisted by NVivo 12. Categories and subcategories were identified through content analysis. RESULTS Twelve and seven early- and late-stage breast cancer patients were included in this study, respectively. The side effects were the main intention of utilizing traditional Chinese medicine. Improving side effects and constitution was the main benefit for patients in both stages. Additionally, early-stage breast cancer patients used traditional Chinese medicine to prevent recurrence or metastasis. Late-stage breast cancer patients responded more frequently to the use of traditional Chinese medicine due to the side effects of western medicine. However, some of their symptoms were not fully relieved. CONCLUSIONS Breast cancer staging may influence the intention and utilization of traditional Chinese medicine. Health policymakers should consider the results of this research and the evidence-based illustrations to establish guidelines for integrating traditional Chinese medicine among various stages of breast cancer to improve the outcome and quality of care for cancer patients.
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Affiliation(s)
- Kai-Wei Chen
- Institute of Health Policy and Management, National Taiwan University, 17 Xuzhou Road, Zhongzheng District, Taipei City, 100, Taiwan
- Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100 Kunming Street, Wanhua District, Taipei City, 108, Taiwan
| | - Kuo-Piao Chung
- Institute of Health Policy and Management, National Taiwan University, 17 Xuzhou Road, Zhongzheng District, Taipei City, 100, Taiwan.
| | - Chung-Hua Hsu
- Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100 Kunming Street, Wanhua District, Taipei City, 108, Taiwan
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Liao Y, Li S, An J, Yu X, Tan X, Gui Y, Wang Y, Huang L, Zhou S, Wang D. Ethyl acetate extract of Antenoron Filiforme inhibits the proliferation of triple negative breast cancer cells via suppressing Skp2/p21 signaling axis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 116:154856. [PMID: 37187035 DOI: 10.1016/j.phymed.2023.154856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 04/11/2023] [Accepted: 05/02/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Triple negative breast cancer (TNBC) has the worst prognosis of the any breast cancer subtype, and the efficient therapeutical treatment is extremely limited. Antenoron filiforme (Thunb.) Roberty & Vautier (AF) is a Traditional Chinese Medicine (TCM), which is well-known for a diverse array of pharmacological activities, including but not limited to anti-inflammatory, antioxidant and anti-tumors properties. Clinically, AF is commonly prescribed for the treatment of gynecological diseases. PURPOSE Since TNBC is one of the worst gynecological diseases, the objective of this research is to study the anti-TNBC function of the ethyl acetate extract (EAE) of AF (AF-EAE) and disclose its mechanism of action. MATERIALS AND METHODS With the aim of elucidating the underlying molecular mechanism and possible chemical basis of AF-EAE in the treatment of TNBC, a comprehensive approach combining system pharmacology and transcriptomic analysis, functional experimental validation, and computational modeling was implemented. Firstly, the potential therapeutic targets of AF-EAE treating TNBC were analyzed by systemic pharmacology and transcriptome sequencing. Subsequently, cell viability assays, cell cycle assays, and transplantation tumor assays were employed to detect the inhibitory effect of AF-EAE on TNBC. Apart from that, the western blot and RT-qPCR assays were adopted to verify its mechanism of action. Finally, the potential chemical basis of anti-TNBC function of AF-EAE was screened through molecular docking and validated by molecular dynamics. RESULTS This study analyzed the differentially expressed genes after AF-EAE treatment by RNA-sequencing (RNA-seq). It was found that most of the genes were abundant in the gene set termed "cell cycle". Besides, AF-EAE could suppress the proliferation of TNBC cells in vitro and in vivo by inhibiting the function of Skp2 protein. AF-EAE could also lead to the accumulation of p21 and a decrease of CDK6/CCND1 protein, thereby stalling the cycle of cell in the G1/S stage. Notably, clinical data survival analysis clearly demonstrated that Skp2 overexpression has been negatively correlated with survival rates in breast cancer (BC) patients. Further, as suggested by molecular docking and molecular dynamics, the quercetin and its analogues of AF-EAE might bind to Skp2 protein. CONCLUSION In summary, AF-EAE inhibits the growth of TNBC in vitro and in vivo through targeting Skp2/p21 signaling pathway. While providing a novel potential drug for treating TNBC, this study might establish a method to delve into the action mechanism of TCM.
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Affiliation(s)
- Yile Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shengrong Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jun An
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xiankuo Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xue Tan
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yu Gui
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yumei Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Lijun Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shiyi Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Dong Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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10
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Li Z, Qi J, Guo T, Li J. Research progress of Astragalus membranaceus in treating peritoneal metastatic cancer. JOURNAL OF ETHNOPHARMACOLOGY 2023; 305:116086. [PMID: 36587879 DOI: 10.1016/j.jep.2022.116086] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Peritoneal metastasis is a manifestation of advanced cancer often associated with a poor prognosis and poor response to treatment. Astragalus membranaceus (Fisch.) Bunge is a commonly used medicinal material in traditional Chinese medicine with various biological activities. In patients with cancer, Astragalus membranaceus has demonstrated anti-tumor effects, immune regulation, postoperative recurrence and metastasis prevention, and survival prolongation. AIM OF THE STUDY Peritoneal metastasis results from tumor cell and peritoneal microenvironment co-evolution. We aimed to introduce and discuss the specific mechanism of action of Astragalus membranaceus in peritoneal metastasis treatment to provide a new perspective for treatment and further research. MATERIALS AND METHODS We consulted reports on the anti-peritoneal metastases effects of Astragalus membranaceus from PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases, as well as Google Scholar. Meanwhile, we also obtained data from published medical works and doctoral and master's theses. Then, we focused on the research progress of Astragalus membranaceus in peritoneal metastatic cancer treatment. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org). RESULTS To date, more than 200 compounds have been isolated from Astragalus membranaceus. Among them, Astragalus polysaccharides, saponins, and flavonoids are the main bioactive components, and their effects on cancer have been extensively studied. In this review, we systematically summarize the effects of Astragalus membranaceus on the peritoneal metastasis microenvironment and related mechanisms, including maintaining the integrity of peritoneal mesothelial cells, restoring the peritoneal immune microenvironment, and inhibiting the formation of tumor blood vessels, matrix metalloproteinase, and dense tumor spheroids. CONCLUSIONS Our analysis demonstrates that Astragalus membranaceus could be a potential therapeutic for preventing the occurrence of peritoneal metastasis. However, it might be too early to recommend its use owing to the paucity of reliable in vivo experiment, clinical data, and evidence of clinical efficacy. In addition, previous studies of Astragalus membranaceus report inconsistent and contradictory findings. Therefore, detailed in vitro, in vivo, and clinical studies on the mechanism of Astragalus membranaceus in peritoneal metastatic cancer treatment are warranted.
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Affiliation(s)
- Zhiyuan Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China
| | - Jinfeng Qi
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China
| | - Tiankang Guo
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, 730030, China
| | - Junliang Li
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, 730030, China; The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, 730030, China; The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730030, China.
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11
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Shiah HS, Lee CJ, Lee FY, Tseng SH, Chen SH, Wang CC. Chemopreventive effects of Xiang Sha Liu Jun Zi Tang on paclitaxel-induced leucopenia and neuropathy in animals. Front Pharmacol 2023; 14:1106030. [PMID: 36969850 PMCID: PMC10032344 DOI: 10.3389/fphar.2023.1106030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 02/16/2023] [Indexed: 03/06/2023] Open
Abstract
Paclitaxel frequently induces peripheral neuropathy and myelosuppression during cancer treatment. According to the National Health Insurance Research Database of Taiwan, traditional Chinese medicine doctors widely use Xiang Sha Liu Jun Zi Tang (XSLJZT) to treat breast cancer patients who have received paclitaxel. We explored the combined therapeutic effects of XSLZJT with paclitaxel. XSLJZT did not exhibit significant cytotoxic effects on P388-D1 cells; however, the combination of XSLJZT (100 and 500 mg/kg) with paclitaxel prolonged the survival rate in P388–D1 tumor-bearing mice compared to paclitaxel-only. In addition, XSLJZT was found to enhance white blood cells (WBC) counts and promote leukocyte rebound in paclitaxel-induced leukopenia in mice. XSLJZT also reduced paclitaxel-induced mechanical pain and inhibited c-Fos protein expression in the L4-6 spinal cords of Wistar rats. Moreover, paclitaxel-induced shortening of the nerve fibers of dorsal root ganglion cells was ameliorated by pre-treatment with XSLJZT. Therefore, we suggest that XSLJZT could be used as an adjunct for cancer patients, as the formula could decrease paclitaxel-induced neuropathy and myelosuppression.
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Affiliation(s)
- Her-Shyong Shiah
- Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Chia-Jung Lee
- Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan
- Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Fang-Yu Lee
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan
| | - Sung-Hui Tseng
- Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shih-Han Chen
- School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Ching-Chiung Wang
- Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan
- Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
- School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- *Correspondence: Ching-Chiung Wang,
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12
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The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients. Cancers (Basel) 2023; 15:cancers15041213. [PMID: 36831555 PMCID: PMC9953925 DOI: 10.3390/cancers15041213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 01/21/2023] [Accepted: 01/29/2023] [Indexed: 02/17/2023] Open
Abstract
Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.
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13
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Chu YR, Kung PT, Liu LC, Lin CY, Ou-Yang F, Yue CH, Su SY, Chen YY, Wang WC, Kao HF, Chou WY, Tsai WC. Comparison of Quality of Life Between Breast Cancer Patients Treated With and Without Adjunctive Traditional Chinese Medicine in Taiwan. Integr Cancer Ther 2023; 22:15347354221150907. [PMID: 36688414 PMCID: PMC9893072 DOI: 10.1177/15347354221150907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 06/27/2022] [Accepted: 12/27/2022] [Indexed: 01/24/2023] Open
Abstract
In Taiwan, breast cancer has the highest incidence among all cancers. Although adjunctive traditional Chinese medicine treatment (TCM) have been used to ameliorate the side effects or discomfort caused by cancer treatments, no study has focused on the assessment of the quality of life of patients undergoing adjunctive TCM treatments. This study compared the quality of life between breast cancer patients treated with and without adjunctive TCM. Questionnaires were collected from 7 hospitals with a Chinese medicine clinic in 2018 to 2019. Breast cancer patients who had cancer stages I, II, or III and also underwent resection surgery were included in the study. They were divided into 2 groups: patients receiving cancer treatments with adjunctive traditional Chinese medicine (TCM group) and those receiving cancer treatments without adjunctive traditional Chinese medicine (non-TCM group). A 1:1 matching was used to obtain the study participants. The EQ-5D questionnaire was used to assess the quality of life. Statistical analysis was performed using the t-test and ANOVA to compare the differences between variables. The conditional multiple regression model was applied to explore the factors associated with quality of life in breast cancer patients. A total of 543 participants were surveyed, and 450 participants were included in the study. The EQ-5D score of the TCM group (81.60 ± 11.67) was significantly higher than that of the non-TCM group (78.80 ± 13.10; P < .05). The results of a conditional multiple regression model showed that the TCM group had a higher (3.45 points) quality of life than non-TCM group (P = .002) after adjusting for other related factors. After stratifying by cancer stage, patients with cancer stages II and III scored 5.58 and 4.35 points higher in the TCM group than did those in the non-TCM group (P < .05). Breast cancer patients undergoing cancer treatment with adjunctive traditional Chinese medicine have a higher quality of life than those treated without adjunctive traditional Chinese medicine.
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Affiliation(s)
| | - Pei-Tseng Kung
- China Medical University, Taichung, Taiwan
- Asia University, Taichung, Taiwan
- China Medical University Hospital, Taichung, Taiwan
| | | | - Chin-Yao Lin
- Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan
| | - Fu Ou-Yang
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | | | - Shan-Yu Su
- China Medical University Hospital, Taichung, Taiwan
| | - Ying-Yu Chen
- China Medical University Hospital, Taichung, Taiwan
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14
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Association between Oral Chinese Herbal Medicine and Recurrence and Metastasis in Patients with Stages II and III Colorectal Cancer: A Cohort Study in China. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:8529395. [DOI: 10.1155/2022/8529395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 09/20/2022] [Indexed: 11/10/2022]
Abstract
Background. To evaluate the associations between long-term oral Chinese herbal medicines (CHMs) and recurrence and metastasis (R&M) in patients with stage II and III colorectal cancer (CRC). Furthermore, we aimed to determine the correlation between different syndrome patterns and prognosis and summarized the regularities among CHMs prescriptions, providing reference for clinical practice. Methods. An ambispective cohort study was conducted. All CRC patients who sought evaluation and treatment at Xiyuan Hospital and Beijing Cancer Hospital from August 2014 to August 2016 were included. In this study, “whether patients voluntarily take CHMs” was taken as the exposure factor, and the exposure degree was “the duration of CHM use.” Stratification was performed according to the duration of TCM use to determine the relationship with R&M of CRC. The primary outcome was disease-free survival. Patients who had R&M of CRC after taking CHMs for ≥6 months were defined as “worst patients.” R software was used for statistical analysis. The Kaplan–Meier method and Cox regression analysis were used to determine the prognosis. IBM SPSS was used to model a priori association rules; drug use rules were analyzed on this basis. Results. A total of 186 patients with stage II and III CRC after radical resection were enrolled. All patients reached the study endpoint by August 2021. The difference in disease-free survival between the two groups was most significant when the cutoff value for CHMs was 18 months (
). Multivariate analysis showed that 18 CHMs were independent protective factors for R&M of CRC (
, HR = 0.20, 95% CI = 0.08–0.53). The ratio of Pi (spleen) and Shen (kidney) deficiency in the worst cases was higher than patients without R&M (
). Sijunzi and Liuwei Dihuang decoctions were the most frequently used prescriptions in the anti-R&M phase. Conclusion. CHMs complying with the “Jianpi Bushen” principle may attenuate the risk of R&M in patients with stage II and III CRC. Pi (spleen) and Shen (kidney) deficiency in patients receiving TCM intervention for the first time within 6 months of radical resection may be associated with a higher CRC R&M rate. Further research is warranted to validate these findings and elucidate underlying biological mechanisms.
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15
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Hung Y, Leung S, Chiu SP, Li P, Kan A, Lo C, Wong SZ, Luk S, Lai CC, El Helali A, Chan WW. Perceptions about traditional Chinese medicine use among Chinese breast cancer survivors: A qualitative study. Cancer Med 2022; 12:1997-2007. [PMID: 36073533 PMCID: PMC9883569 DOI: 10.1002/cam4.5046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 07/04/2022] [Accepted: 07/07/2022] [Indexed: 02/02/2023] Open
Abstract
INTRODUCTION An increasing number of breast cancer survivors (BCS) use traditional Chinese medicine (TCM) throughout their cancer journey. There is emerging evidence that TCM is effective in the reducing side effects of chemotherapy. However, qualitative patient-centric and culturally relevant research into TCM use is scant. This qualitative study aimed to explore the use and perceptions of Chinese Hong Kong BCS using TCM. METHODS Participants were recruited from a university hospital and three breast cancer patient groups in Hong Kong. Questionnaires regarding the use of TCM were given to all participants, followed by individual semi-structured interviews on selected BCS to comprehensively understand TCM's use and perceptions. A greater emphasis was placed on the qualitative data. RESULTS About half of the participants (n = 67, 48.9%) used TCM during their cancer treatment journey, among which almost all (n = 64, 95.5%) had improved symptoms. Sleeping disturbances (n = 58, 86.6%) and fatigue (n = 53, 79.1%) were the two most common symptoms that improved after TCM. Interview data revealed that participants used TCM to satisfy unmet needs that mainstream conventional Western medicine could not fulfil. They wished for a sense of control and better well-being. They expressed improvements in physical and psychological well-being after the use of TCM. Despite existing barriers, including high cost, long duration of treatment, and disapproval from oncologists, most would still recommend TCM to fellow survivors. CONCLUSIONS Chinese Hong Kong BCS who used TCM reported positive experiences. Understanding how BCS perceive and use TCM is important to integrating TCM into survivorship care in this population.
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Affiliation(s)
- Yik‐Laam Hung
- Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | - Siu‐Sing Leung
- Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | | | - Pik‐Yi Li
- Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | | | - Chi‐Chung Lo
- Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | | | - Sze‐Lam Luk
- Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | | | - Aya El Helali
- Department of Clinical Oncology, Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
| | - Wendy Wing‐Lok Chan
- Department of Clinical Oncology, Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong
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Qu J, Ke F, Yang X, Wang Y, Xu H, Li Q, Bi K. Induction of P-glycoprotein expression by dandelion in tumor and heart tissues: Impact on the anti-tumor activity and cardiotoxicity of doxorubicin. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154275. [PMID: 35760022 DOI: 10.1016/j.phymed.2022.154275] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 06/05/2022] [Accepted: 06/11/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Previously, we have investigated the anti-tumor activity and mechanism through which dandelion acts against triple-negative breast cancer (TNBC). However, traditional Chinese medicine is mostly accepted as an adjunct therapy during chemotherapy in clinical practice. So far, little is known about the effects of dandelion in conjunction with chemotherapeutic drugs. PURPOSE To investigate the effects of dandelion on the anti-tumor activity and cardiotoxicity of doxorubicin (DOX), and to further explore the molecular mechanisms through which these effects occur. STUDY DESIGN At the beginning of this study, dandelion was observed to alleviate DOX-induced cardiotoxicity and reduce the anti-tumor activity of DOX. Subsequently, we investigated whether the resistance to DOX mediated by P-glycoprotein was involved in the above effects. METHODS The cardioprotective effect of dandelion was investigated on DOX-treated mice by histological analysis, myocardial enzyme assays, and an untargeted metabolomics study based on LC-Q-TOF/MS. TNBC cell lines and 4T1 tumor-bearing mice were employed to investigate the combined anti-tumor activity. Laser scanning confocal microscope and a flow cytometry analysis were employed to measure the intracellular accumulation of DOX. A specific, sensitive, and rapid LC-MS/MS method was developed to detect the efflux of DOX from cells. Expression of P-glycoprotein in mouse tumor and heart tissues was detected via Western blotting analysis. RESULTS Dandelion was found to significantly alleviate DOX-induced cardiotoxicity, as was evidenced by improved cardiomyocyte morphology, decreased LDH and CK-MB release, and adjusted metabolic biomarker levels. However, in vitro and in vivo studies showed that dandelion could reduce the anti-tumor activity of DOX. This counteraction was achieved by activating of the drug efflux transporter P-glycoprotein, thereby promoting the efflux of DOX from cells and reducing the intracellular accumulation of DOX. Moreover, the activation of P-glycoprotein by dandelion in mouse heart tissue was also observed, thus suggesting that the decrease of cardiac DOX accumulation plays an important role in the cardioprotective effect of dandelion. CONCLUSION Dandelion can activate the P-glycoprotein in heart and tumor tissues, which ameliorates DOX-induced cardiotoxicity but attenuates DOX cytotoxicity toward TNBC. Our findings have important implications for the correct clinical use of dandelion.
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Affiliation(s)
- Jiameng Qu
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Fan Ke
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xiao Yang
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Yue Wang
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Huarong Xu
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Qing Li
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Kaishun Bi
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
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Hedyotis diffusae Herba-Andrographis Herba inhibits the cellular proliferation of nasopharyngeal carcinoma and triggers DNA damage through activation of p53 and p21. Cancer Gene Ther 2022; 29:973-983. [PMID: 34754077 DOI: 10.1038/s41417-021-00385-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 08/08/2021] [Accepted: 08/27/2021] [Indexed: 12/25/2022]
Abstract
Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.
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Qu J, Ke F, Liu Z, Yang X, Li X, Xu H, Li Q, Bi K. Uncovering the mechanisms of dandelion against triple-negative breast cancer using a combined network pharmacology, molecular pharmacology and metabolomics approach. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 99:153986. [PMID: 35183931 DOI: 10.1016/j.phymed.2022.153986] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/16/2022] [Accepted: 02/10/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Taraxacum mongolicum, also called dandelion, has been used for thousands of years as a remedy for mammary abscess, mammary gland hyperplasia, and various other diseases afflicting the breast. In modern pharmacological research, dandelion has been proven to be effective against triple-negative breast cancer (TNBC). However, the mechanisms of this anti-tumor effect have not been fully elucidated. PURPOSE The aim of this investigation was to understand the multi-target mechanisms through which dandelion counteracts TNBC via a network pharmacology strategy as well as to validate its effectiveness by means of molecular pharmacology and metabolomics assessments. METHODS A liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (LC-Q-TOF/MS) was employed to identify the absorbed components of dandelion in rat plasma. The network pharmacology-based prediction was utilized to uncover the potential mechanisms through which dandelion counteracts TNBC, during which potential targets were identified and pathway enrichment analysis was performed. Subsequently, TNBC cells and 4T1 tumor-bearing mice were used to further verify the molecular mechanisms of dandelion. RESULTS Twelve active compounds were identified in rat plasma, which were connected with 50 TNBC-related targets. The pathway enrichment showed that dandelion could treat TNBC through regulating a series of biological processes involving cell cycle and metabolism. Experimentally, flow cytometry analysis revealed that dandelion could arrest the G0/G1 and G2/M cell cycles in 4T1 cells. Further western blot analysis evidenced that the protein expression of kinase 6 (CDK6) as well as cyclins B1 and B2 in mice tumor tissue were suppressed by dandelion. In addition, cell metabolomics analysis revealed the changes in the endogenous metabolite levels that result from dandelion treatments, such as the downregulation of arginine and spermine levels. All these findings were consistent with the predicted targets and pathways. CONCLUSION This study comprehensively demonstrates the multi-target mechanisms of dandelion against TNBC using network pharmacology, molecular pharmacology, and metabolomics approaches. These findings will provide important stepping stones for further mechanism investigations and may lead to the development of highly effective dandelion-based treatments for TNBC.
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Affiliation(s)
- Jiameng Qu
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Fan Ke
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Ziru Liu
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xiao Yang
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Xianzhe Li
- School of Traditional Chinese Material Medica, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Huarong Xu
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Qing Li
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Kaishun Bi
- National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
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Kapelemera AM, Uang YS, Wang LH, Wu TY, Lee FY, Tai L, Wang CC, Lee CJ. Pharmacokinetic Herb-Drug Interactions of Xiang-Sha-Liu-Jun-Zi-Tang and Paclitaxel in Male Sprague Dawley Rats and Its Influence on Enzyme Kinetics in Human Liver Microsomes. Front Pharmacol 2022; 13:858007. [PMID: 35450043 PMCID: PMC9016196 DOI: 10.3389/fphar.2022.858007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Abstract
Paclitaxel is a prescribed anticancer drug used to treat various cancers. It is a substrate of cytochrome P-450 (CYP-450) enzymes. Despite its efficacy, paclitaxel has severe side effects. Herbal medicines are commonly used to treat the side effects of chemotherapy. They can be administered before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is a herbal formula commonly used in breast cancer patients. The main purpose of this study was to assess the pharmacokinetic (PK) influence of XSLJZT on paclitaxel PK parameters, determine its effect on CYP-450 enzyme expression, and evaluate its effect on enzyme activity. Sprague Dawley rats were classified into pretreatment and co-treatment groups, where XSLJZT was pre-administered for 3, 5, and 7 days and co-administered 2 h before paclitaxel administration. The rat liver tissues and Hep-G2 cells were used to determine the effects of XSLJZT on CYP3A1/2 and CYP3A4 enzymes respectively. Western blot analysis was used to detect changes in the CYP3A1/2 and CYP3A4 enzymes expression. The influence of XSLJZT on enzyme activity was evaluated using human liver microsomes, and a liquid chromatography-tandem mass spectrometric system was developed to monitor paclitaxel levels in rat plasma. Results demonstrated that XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel in pretreatment groups by 2-, 3-, and 4-fold after 3, 5, and 7 days, respectively. In contrast, no significant change in the AUC was observed in the co-treatment group. However, the half-life was prolonged in all groups from 17.11 min to a maximum of 37.56 min. XSLJZT inhibited CYP3A1/2 expression in the rat liver tissues and CYP3A4 enzymes in Hep-G2 cells in a time-dependent manner, with the highest inhibition observed after 7 days of pretreatment in rat liver tissues. In the enzyme kinetics study, XSLJZT inhibited enzyme activity in a competitive dose-dependent manner. In conclusion, there is a potential interaction between XSLJZT and paclitaxel at different co-treatment and pretreatment time points.
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Affiliation(s)
- Alinafe Magret Kapelemera
- PhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yow-Shieng Uang
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.,Rosetta Pharmamate Co., Ltd, New Taipei City, Taiwan
| | - Li-Hsuan Wang
- School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Tien-Yuan Wu
- Department of Pharmacology, School of Medicine, College of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Fang-Yu Lee
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan
| | - Li Tai
- Rosetta Pharmamate Co., Ltd, New Taipei City, Taiwan
| | - Ching-Chiung Wang
- PhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.,School of Pharmacy, Taipei Medical University, Taipei, Taiwan.,Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Chia-Jung Lee
- PhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan.,Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.,Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
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A Perspective on Tongue Diagnosis in Patients with Breast Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2021:4441192. [PMID: 34987592 PMCID: PMC8720603 DOI: 10.1155/2021/4441192] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/14/2021] [Accepted: 11/30/2021] [Indexed: 11/29/2022]
Abstract
Introduction Breast cancer (BC) is the most common cancer in women and patients with BC often undergo complex treatment. In Taiwan, nearly 80% of patients with BC seek traditional Chinese medicine (TCM) during adjuvant chemotherapy to relieve discomfort and side effects. This study investigated tongue features and pattern differentiation through noninvasive TCM tongue diagnosis in patients with BC. Materials and Methods This cross-sectional, case-controlled, retrospective observational study collected patient data through a chart review. The tongue features were extracted using the automatic tongue diagnosis system (ATDS). Nine tongue features, including tongue shape, tongue color, fur thickness, fur color, saliva, tongue fissures, ecchymoses, teeth marks, and red dots, were analyzed. Results and Discussion. Objective image analysis techniques were used to identify significant differences in the many tongue features between BC patients and non-BC individuals. A significantly larger proportion of patients with BC had a small tongue (p < 0.001), pale tongue (p < 0.001), thick fur (p < 0.001), yellow fur (p < 0.001), wet saliva (p < 0.001), thick tongue fur (p < 0.001), fissures (p=0.040), and ecchymoses in the heart-lung area (p=0.013). According to logistic regression, small tongue shape, pale tongue color, yellow fur color, wet saliva, and the amounts of fissures were associated with a significantly increased odds ratio for BC. Conclusions This study showed significant differences in tongue features, such as small tongue shape, pale tongue color, thick fur, yellow fur color, wet saliva, fissure, and ecchymoses in the heart-lung area in patients with BC. These tongue features would imply yin deficiency, deficiencies of blood, stagnation of heat, and phlegm/blood stasis in TCM theory. There is a need to investigate effective and safe treatment to enhance the role of TCM in integrated medical care for patients with BC.
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21
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Effect of Combining Traditional Chinese Medicine with Hormonal Therapy on Quality of Life and Tumor Markers of Prostate Cancer Patients. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5061867. [PMID: 34691216 PMCID: PMC8528605 DOI: 10.1155/2021/5061867] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 09/28/2021] [Indexed: 11/17/2022]
Abstract
Objective To explore the effect of combining traditional Chinese medicine (TCM) with hormonal therapy on the quality of life and tumor markers of prostate cancer patients. Methods A total of 60 prostate cancer patients treated in Zibo Central Hospital from June 2017 to June 2021 were selected for the retrospective analysis study and divided into the control group and experimental group based on whether applying TCM treatment, with 30 cases each. The patients in the experimental group received the combined treatment of TCM and hormonal therapy, and those in the control group only accepted the hormonal therapy, so as to analyze their clinical efficacy and tumor marker levels after treatment. Results The patients' general information were not statistically different (P > 0.05); after treatment, the levels and ratios of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) of patients in both groups were improved, and the experimental group obtained significantly lower TPSA and FPSA levels (P < 0.05) and higher TPSA/FPSA ratios (P < 0.05); the incidence of androgen-independent prostate cancer was significantly lower in the experimental group than in the control group (8 vs. 16, P < 0.05); in addition, the time to develop into the androgen-independent prostate cancer was longer in patients of the experimental group than those of the control group (P < 0.05); the treated patients in the experimental group obtained obviously higher Functional Assessment of Cancer Therapy-Prostate (FACT-P) quality of life scores and Karnofsky score (KPS) than those in the control group (P < 0.05), and the number of patients with recovered PSA levels was significantly higher in the experimental group than in the control group (P < 0.05). Conclusion Combining self-made TCM formula with hormonal therapy can effectively improve the levels of prostate tumor markers and postpone the progress of developing from prostate cancer to androgen-independent prostate cancer, which is conducive to promoting the patients' quality of life.
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22
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Li J, Wang S, Wang N, Zheng Y, Yang B, Wang X, Zhang J, Pan B, Wang Z. Aiduqing formula inhibits breast cancer metastasis by suppressing TAM/CXCL1-induced Treg differentiation and infiltration. Cell Commun Signal 2021; 19:89. [PMID: 34461944 PMCID: PMC8404313 DOI: 10.1186/s12964-021-00775-2] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 08/08/2021] [Indexed: 12/25/2022] Open
Abstract
Background Metastasis represents the leading cause of death in patients with breast cancer. Traditional Chinese medicine is particularly appreciated for metastatic diseases in Asian countries due to its benefits for survival period prolongation and immune balance modulation. However, the underlying molecular mechanisms remain largely unknown. This study aimed to explore the antimetastatic effect and immunomodulatory function of a clinical formula Aiduqing (ADQ). Methods Naive CD4+ T cells, regulatory T cells (Tregs), and CD8+ T cells were sorted by flow cytometry. Then, breast cancer cells and these immune cells were co-cultured in vitro or co-injected into mice in vivo to simulate their coexistence. Flow cytometry, ELISA, qPCR, double luciferase reporter gene assay, and chromatin immunoprecipitation assay were conducted to investigate the immunomodulatory and antimetastatic mechanisms of ADQ. Results ADQ treatment by oral gavage significantly suppressed 4T1-Luc xenograft growth and lung metastasis in the orthotopic breast cancer mouse model, without noticeable hepatotoxicity, nephrotoxicity, or hematotoxicity. Meanwhile, ADQ remodeled the immunosuppressive tumor microenvironment (TME) by increasing the infiltration of tumor-infiltrating lymphocytes (TILs) and cytotoxic CD8+ T cells, and decreasing the infiltration of Tregs, naive CD4+ T cells, and tumor-associated macrophages (TAMs). Molecular mechanism studies revealed that ADQ remarkably inhibited CXCL1 expression and secretion from TAMs and thus suppressed the chemotaxis and differentiation of naive CD4+ T cells into Tregs, leading to the enhanced cytotoxic effects of CD8+ T cells. Mechanistically, TAM-derived CXCL1 promoted the differentiation of naive CD4+ T cells into Tregs by transcriptionally activating the NF-κB/FOXP3 signaling. Lastly, mouse 4T1-Luc xenograft experiments validated that ADQ formula inhibited breast cancer immune escape and lung metastasis by suppressing the TAM/CXCL1/Treg pathway. Conclusions This study not only provides preclinical evidence supporting the application of ADQ in inhibiting breast cancer metastasis but also sheds novel insights into TAM/CXCL1/NF-κB/FOXP3 signaling as a promising therapeutic target for Treg modulation and breast cancer immunotherapy.![]()
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