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Bian JY, Feng YF, He WT, Zhang T. Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine. World J Clin Oncol 2025; 16:93670. [PMID: 39867731 PMCID: PMC11528896 DOI: 10.5306/wjco.v16.i1.93670] [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: 03/03/2024] [Revised: 09/04/2024] [Accepted: 10/11/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer (mCRC) have a low incidence rate, poor biological activity, suboptimal response to conventional treatments, and a poor prognosis. In the previous cohort study on mCRC conducted by our team, it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival (OS) of patients with colorectal cancer. Therefore, we further explored the survival benefits in the population with BRAF V600E mutant mCRC. AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer. METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022. The patients were divided into two cohorts. RESULTS A total of 34 cases were included, with 23 in Chinese-Western medicine cohort (cohort A) and 11 in Western medicine cohort (cohort B). The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B, with a statistically significant difference (P = 0.038, hazard ratio = 0.46). The 1-3-year survival rates were 95.65% (22/23), 39.13% (9/23), and 26.09% (6/23) in cohort A, and 63.64% (7/11), 18.18% (2/11), and 9.09% (1/11) in cohort B, respectively. Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon, liver metastasis, chemotherapy, and first-line treatment subgroups (P < 0.05). CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer, with more pronounced benefits observed in patients with right colon involvement, liver metastasis, combined chemotherapy, and first-line treatment.
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Affiliation(s)
- Jiang-Yu Bian
- Department of Oncology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Yu-Fang Feng
- Department of Oncology, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi 830001, China
| | - Wen-Ting He
- Department of Oncology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi 830001, China
| | - Tong Zhang
- Department of Oncology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
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Gao J, Tan W, Yuan L, Wang H, Wen J, Sun K, Chen X, Wang S, Deng W. Antitumour mechanisms of traditional Chinese medicine elicited by regulating tumour-associated macrophages in solid tumour microenvironments. Heliyon 2024; 10:e27220. [PMID: 38463777 PMCID: PMC10923716 DOI: 10.1016/j.heliyon.2024.e27220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 02/06/2024] [Accepted: 02/26/2024] [Indexed: 03/12/2024] Open
Abstract
Tumour-associated macrophages (TAMs), particularly M2-TAMs, constitute the largest proportion of immune cells in the solid tumour microenvironment, playing a crucial role in tumour progression and correlating with poor prognosis. TAMs promote the proliferation, invasion, and metastasis of tumour cells by remodelling the extracellular matrix, inhibiting immunity, promoting immune escape and tumour angiogenesis, and affecting cell metabolism. Traditional Chinese medicine (TCM) has been used clinically in China for millennia. Chinese herbs exhibit potent antitumour effects with minimal to no toxicity, substantially contributing to prolonging the lives of patients with cancer and improving their quality of life. TCM has unique advantages in improving the solid tumour microenvironment, particularly in regulating TAMs to further inhibit tumour angiogenesis, reduce drug resistance, reverse immunosuppression, and enhance antitumour immunity. This review highlights the TAM-associated mechanisms within the solid tumour microenvironment, outlines the recent advancements in TCM targeting TAMs for antitumour effects, emphasises the superiority of combining TCM with standard treatments or new nano-drug delivery systems, and evaluates the safety and efficacy of TCM combined with conventional treatments via clinical trials to provide insights and strategies for future research and clinical treatment.
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Affiliation(s)
- Jiamin Gao
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Weishan Tan
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Luyun Yuan
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Haoyue Wang
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Junkai Wen
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Kexiang Sun
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Xin Chen
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Shuyun Wang
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
| | - Wanli Deng
- Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200135, China
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Gu Z, Wang L, Zhai MA J, Zhang T, Yang Y. Conventional Therapy Combined With Quxie Capsule Modulating Gut Microbiome in Metastatic Colorectal Cancer Patients With the Third or Above Line Setting: Result From an Investigator-Initiated, Open-Label, Single-Arm, Phase II Study. Integr Cancer Ther 2024; 23:15347354241280390. [PMID: 39313964 PMCID: PMC11425756 DOI: 10.1177/15347354241280390] [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: 03/27/2024] [Revised: 08/17/2024] [Accepted: 08/19/2024] [Indexed: 09/25/2024] Open
Abstract
BACKGROUND In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)-a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)-has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. METHODS A Simon's Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients' stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. RESULTS Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae, Eubacterium and Lachnospiraceae_UCG-001. CONCLUSIONS Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR2100053874).
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Affiliation(s)
- Zhien Gu
- China Academy of Chinese Medical Sciences, Beijing, China
| | - Lei Wang
- Chongqing University Three Gorges Hospital, Chongqing, China
| | - Jiawei Zhai MA
- Beijing Chaoyang Integrative Medicinerescue and First Aid Hospital, Beijing, China
| | - Tong Zhang
- China Academy of Chinese Medical Sciences, Beijing, China
| | - Yufei Yang
- China Academy of Chinese Medical Sciences, Beijing, China
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Xu B, Wang X, Wang H, Cao L, Ge Y, Yuan B, Gao R, Li J. Efficacy and safety of herbal formulas with the function of gut microbiota regulation for gastric and colorectal cancer: A systematic review and meta-analysis. Front Cell Infect Microbiol 2022; 12:875225. [PMID: 35992176 PMCID: PMC9386000 DOI: 10.3389/fcimb.2022.875225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 07/04/2022] [Indexed: 01/20/2023] Open
Abstract
Background Currently, gastric cancer (GC) and colorectal cancer (CRC) are the most common causes of cancer-related mortality worldwide. Gut microbiota is closely related to the occurrence of GC and CRC and the efficacy of chemotherapy. This study is aimed at evaluating the efficacy and safety of herbal formulas with the function of gut microbiota regulation (HFGMR) in the treatment of GC and CRC and to assess the quality of the synthesized evidence. Methods A comprehensive search was performed on eight electronic databases, PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and two registries, Chinese Clinical Trial Registry and ClinicalTrials.gov, from their initiation to January 2022. Randomized controlled trials (RCTs) studying the therapeutic effects of HFGMR were included. We used Stata 16 for data synthesis and Risk of Bias 2 (RoB 2) for methodological quality evaluation and assessed the quality of the synthesized evidence in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results Fifty-three RCTs involving 4,478 patients were included. These trials involve seven herbal formulas that could regulate the gut microbiota of Bifidobacterium, Lactobacillus, Escherichia coli, Bacteroides, and Enterococcus faecalis. The meta-analysis results were subgrouped to three different stages in GC and CRC. 1) For the perioperative stage, HFGMR combined with conventional therapy could shorten the time to bowel sound recovery by 1.63 h [mean difference (MD) = -1.63, 95% confidence interval (CI) (-2.62, -0.65)], the time to first flatus by 9.69 h [MD = -9.69, 95% CI (-10.89, -8.48)], and the duration of hospitalization by 2.91 days [MD = -2.91, 95% CI (-4.01, -1.80)] in GC. There were no significant differences in outcomes of gastrointestinal function recovery and adverse events in CRC. 2) For postoperative patients, combined with adjuvant chemotherapy, HFGMR could decrease the incidence of diarrhea, nausea and vomiting, anorexia, and peripheral neurotoxicity in GC; boost Karnofsky performance status (KPS) improvement rate [risk ratio (RR) = 1.96, 95% CI (1.38, 2.79)]; and decrease the incidence of leucopenia and nausea and vomiting in CRC. 3) For advanced stage, HFGMR can significantly improve the objective response rate (ORR) [RR = 1.35, 95% CI (1.19~1.53)], disease control rate (DCR) [RR = 1.14, 95% CI (1.05~1.23)], and KPS improvement rate [RR = 1.56, 95% CI (1.17, 2.09)] and decrease the incidence of leucopenia, neutropenia, anemia, nausea and vomiting, diarrhea, and fatigue in GC. There were no significant differences in ORR [RR = 1.32, 95% CI (0.94~1.86)] and DCR [RR = 1.22, 95% CI (0.99~1.50)], but they can improve the KPS response rate [RR = 1.62, 95% CI (1.13, 2.32)] and decrease the incidence of myelosuppression, nausea and vomiting, diarrhea, and hepatic and renal dysfunction in CRC. Conclusion This study indicates that herbal formulas that could regulate the composition and proportion of gut microbiota have a positive effect in three stages (perioperative, postoperative, and advanced) of GC and CRC. They could promote the recovery of postoperative gastrointestinal function, increase tumor response, improve performance status, and reduce the incidence of adverse events. Herbal formulas exerted anti-cancer efficacy through multiple mechanisms and pathways; among them, the regulation of gut microbiota has not been paid enough attention. To further support the conclusion and better understand the role of gut microbiota in the treatment of GC and CRC, more rigorously designed, large-scale, and multicenter RCTs that focus on herbal formulas and gut microbiota are needed in the future.
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Affiliation(s)
- Bowen Xu
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xinmiao Wang
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Heping Wang
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Luchang Cao
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuansha Ge
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Bo Yuan
- Department of Rheumatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruike Gao
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Li
- Department of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Zhang Z, Chen Y, Zheng Y, Wang L, Shen S, Yang G, Yang Y, Wang T. Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing A. fumigatus-induced Aerobic Glycolysis. Integr Cancer Ther 2022; 21:15347354221138534. [PMID: 36412281 PMCID: PMC9706055 DOI: 10.1177/15347354221138534] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 10/12/2022] [Accepted: 10/27/2022] [Indexed: 11/07/2023] Open
Abstract
AIM Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. METHODS A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. RESULTS QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8+ T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus, Bifidobacterium and Faecalibacterium genera. What's more, opportunistic pathogens, Bacteroides genera and Aspergillus-Aspergillus fumigatus, exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus-induced glycolytic metabolism of colon cancer cells. CONCLUSIONS QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus-induced aerobic glycolysis of colon cancer cells.
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Affiliation(s)
- Zhiyong Zhang
- The State Key Laboratory of
Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing
University, Nanjing, China
- Jiangsu Key Laboratory of Molecular
Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing,
China
| | - Yuxi Chen
- The State Key Laboratory of
Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing
University, Nanjing, China
- Jiangsu Key Laboratory of Molecular
Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing,
China
| | - Yaojun Zheng
- The State Key Laboratory of
Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing
University, Nanjing, China
- Jiangsu Key Laboratory of Molecular
Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing,
China
| | - Lei Wang
- Clinical Cancer Center of Xiyuan
Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Sunan Shen
- The State Key Laboratory of
Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing
University, Nanjing, China
- Jiangsu Key Laboratory of Molecular
Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing,
China
| | - Geliang Yang
- Department of Medicine, Shanghai
Clinical Research Center, Shanghai, China
| | - Yufei Yang
- Clinical Cancer Center of Xiyuan
Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tingting Wang
- The State Key Laboratory of
Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing
University, Nanjing, China
- Jiangsu Key Laboratory of Molecular
Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing,
China
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