Background Bile acids (BAs), once often considered tumor-promoting, are now recognized for their complex roles in breast cancer. Their effects are influenced by the gut microbiota and may vary across cancer subtypes and exposure contexts. Objectives This systematic review aims to summarize the current evidence on the clinical relevance, molecular mechanisms, and therapeutic applications of BAs in breast cancer. Methods We performed a systematic literature search of four international (PubMed, Web of Science, Embase, Cochrane Library) and two Chinese (China National Knowledge Infrastructure, Wanfang) databases, along with clinical trial registries, from inception to February 8, 2026. Study selection adhered to PRISMA guidelines, and we focused on original studies investigating the role of BAs in breast cancer pathogenesis, therapy, or drug development. Results Evidence mapping across clinical profiling, receptor biology, direct BA interventions, and translational applications indicates that human BA measurements do not converge on a stable systemic “BA signature”. Our qualitative heterogeneity assessment indicates that the apparent contradictions are largely driven by differences in exposure compartment, comparator definition, analytical platform and BA speciation/coverage, and variable control of clinical confounders and subtype/stage or treatment background. When these sources of heterogeneity are considered, more coherent patterns emerge: receptor studies support context-dependent outputs across tumor subtypes and microenvironmental states, while direct BA interventions report both anti-tumor and pro-tumor phenotypes that depend strongly on BA species/form and concentration, with many in vitro experiments using pharmacologic or supraphysiologic exposures. In translational research, BAs have been explored as active derivatives targeting defined pathways and as enabling components in drug delivery systems. In the latter setting, BAs mainly serve as biocompatible scaffolds to improve delivery of established chemotherapeutics in preclinical models. Conclusion The BA system represents a promising but challenging therapeutic target for breast cancer. However, its clinical translation requires carefully designed strategies to overcome major hurdles. The inherent lack of tissue specificity poses risks for systemic toxicity. Future efforts must focus on developing tumor-targeted approaches, understanding the gut-microbiome-liver-breast axis, and performing subtype-stratified (especially estrogen receptor status-stratified) research to establish robust patient stratification biomarkers and safely realize the potential of BA-based therapies.
INTRODUCTION:Breast Cancer (BC) is one of the most prevalent malignant tumors in women. The incidence of estrogen receptor-positive (ER+) breast cancer is as high as 70%, and it is increasing. Amorphophalli rhizoma (APR) has the potential to be used in breast cancer. AIMS:The objectives of the present study were to explore the impact of different APR extracts on the proliferation, migration, and invasion of ER+BC and to investigate their possible mechanism at the molecular level. METHODS:Various extracts of APR were prepared in different solvents, such as petroleum ether, ethyl acetate, n-butanol, and water. ER+ T47D breast cancer cell lines were acquired and utilized to assess the effect of APR extracts on ER+ BC. Cell viability was assessed using the cell counting kit8 (CCk8) method, while anti-invasive and migratory effects were examined by transwell and wound healing assay. All the extracts were initially screened, and the ethyl acetate fraction (APR-EA) was found to be the most effective. Ultra High-Performance Liquid Chromatography (UHPLC) of APR-EAE extract revealed the presence of various phytochemicals, such as succinic acid, 2-methoxy resorcinol, penicillic acid, morphine, salicylic acid, α-linolenic acid, and linolenic acid. Flow cytometry, western blot, and immunohistochemistry were used to explore molecular mechanisms. RESULTS:APR-EA demonstrated anti-proliferative, anti-migratory, and anti-invasive effects on the ER+ T47D cell line. Thus, APR-EAE might inhibit the expression of P-PI3K/PI3K and PAkt/ Akt proteins, which subsequently represses the expression of ERα. This inhibition affects the downstream expression of the proteins CDK4 and Bcl-2, which are linked to cell growth and apoptosis. CONCLUSION:Additionally, APR-EA might increase the expression of P21 and Bax proteins, which are associated with cell cycle arrest and apoptosis. Overall, these effects contribute to the anti-ER+ breast cancer properties of APR-EA.
Background and AimThis study, alongside clinical specimens, investigated the inhibitory effect of konjac petroleum ether extract on the migration, invasion, and epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells via the OLFML2A gene, with the objective of elucidating the potential efficacy and mechanism of action of konjac petroleum ether extract.Experimental ProcedureHistopathological examination of OLFML2A was performed on TNBC tumor specimens (n = 8). mRNA and protein levels of OLFML2A and EMT markers (E-cadherin, N-cadherin, vimentin, elastin) were analyzed via qPCR and Western blot. OLFML2A-knockout MDA-MB-231 cells were treated with gradient concentrations of konjac petroleum ether extract. Cell migration (wound healing assay), adhesion, and invasion (Transwell assay) were evaluated, and EMT marker expression was further examined using qPCR, Western blot, and immunofluorescence (n = 3).ResultsIn TNBC patients with high OLFML2A expression, reduced E-cadherin and increased N-cadherin, vimentin, and elastin were observed, while low OLFML2A cases exhibited no significant EMT changes. In MDA-MB-231 cells, OLFML2A knockdown significantly reduced migration and invasion while upregulating E-cadherin and downregulating mesenchymal markers, phenocopying the effects of konjac petroleum ether extract treatment. Konjac extract inhibited cell proliferation with an IC50 of 220 μg/mL at 48 h. The extract inhibited migration and invasion in a dose-dependent manner, with significant effects observed at 200 μg/mL, though potential contributions from cytotoxicity at 300 μg/mL cannot be entirely excluded.ConclusionThe research findings suggest that konjac petroleum ether extract inhibits TNBC cells migration and invasion by modulating OLFML2A to inhibit EMT. These findings highlight its potential as a candidate for further investigation for preventing TNBC metastasis, though the contribution of cytotoxicity at higher concentrations warrants further investigation.
BackgroundTriple-negative breast cancer (TNBC) is recognized as one of the most aggressive and prognostically adverse subtypes of breast cancer. The lack of effective therapeutic targets presents substantial challenges, including impediments in early diagnosis, restricted treatment options, and a pronounced tendency for drug resistance. Despite recent advancements in the diagnosis and management of TNBC, the overall survival rate for patients remains suboptimal. Consequently, gaining a more profound understanding of its biological mechanisms and developing novel therapeutic strategies are imperative scientific priorities in this domain.MethodsOLFML2A was identified as a potential therapeutic target in TNBC through analyses of the Human Protein Atlas and Kaplan-Meier databases. Its functional role was investigated using OLFML2A knockout (KO) and overexpression (OE) models in MDA-MB-231 cells. Effects on proliferation, cell cycle, and apoptosis were assessed by EdU assays, flow cytometry, RT-qPCR, western blotting, and immunofluorescence. Tumor growth and body weight were monitored in vivo, and tumor tissues were examined by H&E staining, RT-qPCR, and western blotting. Proteomic profiling integrated with literature mining identified EZH2 as a key downstream candidate. Their interaction was validated by co-immunoprecipitation, and EZH2 expression and localization under different OLFML2A conditions were analyzed. Rescue experiments using the EZH2 inhibitor GSK126 assessed the functional output of the OLFML2A-EZH2 axis via CCK-8, EdU assays.ResultsOLFML2A acts as an oncogenic gene in triple-negative breast cancer. The silencing of OLFML2A markedly reduced the proliferation of MDA-MB-231 cells, induced cell cycle arrest at the G1 phase, and inhibited tumor growth. In contrast, overexpression of OLFML2A reversed these effects. Comprehensive proteomic and molecular biology analyses further indicated that OLFML2A may play a role in cell cycle regulation through the modulation of EZH2.ConclusionsOur findings suggest that OLFML2A may facilitate cell cycle progression by regulating EZH2, implicating it as a potential therapeutic target for triple-negative breast cancer.
Background : Ulcerative non-puerperal mastitis (NPM) is characterized by delayed healing and high recurrence. Effective pharmacological options are limited. Objective : This study aimed to evaluate the efficacy and safety of Kangfuxin Solution (KFX) irrigation and to examine whether pathological subtype influences treatment response. Methods : A prospective single-center randomized controlled trial was conducted using a 2×2 factorial design. A total of 240 patients with ulcerative plasma cell mastitis (PCM) or granulomatous lobular mastitis (GLM) were randomly assigned to receive KFX irrigation or normal saline irrigation, in addition to standardized oral therapy. Primary outcomes were therapeutic response assessed by an ordinal scale at one year. Secondary outcomes included inflammatory mass size, pain scores, recurrence, intervention duration, and safety. Analyses were performed in both intention-to-treat and per-protocol populations. Results : KFX irrigation significantly improved therapeutic efficacy versus saline control in both the per-protocol (OR=2.0, 95% CI: 1.2-3.3) and intention-to-treat (OR=1.9, 95% CI: 1.2-3.1) analyses, with a more pronounced benefit observed in PCM patients. A significant intervention × pathology × time interaction was observed for inflammatory mass size (P < 0.001), with the most pronounced reduction in the GLM-KFX group during the first three months. Furthermore, KFX significantly reduced pain scores (mean difference: -1.01) and recurrence rates (OR=0.24), while demonstrating a comparable safety profile to the control. Conclusions : KFX irrigation is a safe and effective adjunctive therapy for ulcerative NPM. The findings indicate favorable effects on pain relief and recurrence prevention and suggest that pathological subtype may influence treatment responsiveness.
Background:Breast cancer is the second most common cancer worldwide. Chemotherapy often causes dyslipidemia and obesity in breast cancer patients. Monitoring lipid profiles and body mass index (BMI) is crucial to evaluate chemotherapy's metabolic side effects, identify interventions to mitigate them, and understand health risks linked to weight changes during treatment. Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM), treats spleen-stomach ailments by boosting spleen function, enhancing qi, and reducing dampness. SLBZP has potential benefits in managing chemotherapy-induced dyslipidemia and improving overall metabolic health in cancer patients. This study retrospectively examined the effects of SLBZP on blood lipid levels and BMI in breast cancer patients undergoing adjuvant chemotherapy. Methods:This study reviewed the medical records of patients who were diagnosed with breast cancer at the Breast Surgery Department of Zhejiang Provincial Hospital of Traditional Chinese Medicine from January 2022 to December 2023. Based on the inclusion criteria, a total of 180 eligible patients were included and divided into an observational group (which received SLBZP) and a control group (which did not receive SLBZP) during chemotherapy. Patients' clinical data, including age at diagnosis, menopausal status, tumor location, smoking and drinking habits, tumor molecular type, tumor node metastasis (TNM) stage, chemotherapy drugs, targeted therapy, lipid levels, and BMI before and after chemotherapy, were collected. Statistical analyses were conducted using SPSS 25.0. Results:After chemotherapy, the control group showed significant increases in total cholesterol (TC) (P=0.03), triglyceride (TG) (P=0.001), low-density lipoprotein cholesterol (LDL-C) (P=0.02), and apolipoprotein B (ApoB) (P=0.01) levels. In the observational group, the TC, TG, and LDL-C levels remained stable (P>0.05), but the high-density lipoprotein cholesterol (HDL-C) (P=0.001) and apolipoprotein A1 (ApoA1) (P<0.001) levels significantly decreased, and BMI (P=0.02) significantly increased. The subgroup analysis revealed that the taxane followed by anthracycline subgroup showed significant increases in BMI (P=0.007) and significant decreases in the HDL-C (P=0.007) and ApoA1 (P<0.001) levels, while the taxane subgroup showed a significant decrease in the HDL-C level post-chemotherapy (P=0.003). In the control group, the TG (P=0.002) and LDL-C (P=0.02) levels were significantly elevated in the taxane followed by anthracycline subgroup post-chemotherapy. No significant changes were observed in BMI or the other lipid indexes in the remaining chemotherapy drug regime subgroups (P>0.05). Conclusions:Chemotherapy increased the TC, TG, LDL-C, and ApoB levels in breast cancer patients, but SLBZP mitigated dyslipidemia. The patients who received SLBZP also showed increased BMI post-chemotherapy, which was likely due to reduced gastrointestinal side effects. Taxane-based chemotherapy drugs had greater effects on blood lipids and BMI, while anthracycline-based drugs did not significantly affect blood lipids and BMI.
A crucial aspect of the association involving inflammation and the development of cancer is the ability of cancer cells to undergo a transition into mesenchymal cells. The process is referred to as epithelial-mesenchymal transition (EMT). Cytokines and chemokines, which are inflammatory agents found in the carcinoma microenvironment, induce epithelial-mesenchymal transition (EMT) changes in malignant cells. Evaluating the role of cytokines in EMT in breast carcinoma and investigating their potential therapeutic implications is the objective of this comprehensive research report. The following search criteria were applied to the Cochrane, Embase, PubMed, and Web of Science databases: “cytokines,” “the cytokines,” “chemokines,” “EMT,” “epithelial-mesenchymal transition or transformation,” “breast tumor,” “breast carcinoma,” and “breast cancer.” A body of research comprising 54 articles has demonstrated that a number of cytokines, including TNF-α, TGF-β, and IL-6, contribute to the promotion of EMT alterations in breast tumors. The epithelial markers E-cadherin and β-catenin were downregulated as a consequence of morphological changes induced by EMT; conversely, the mesenchymal markers N-cadherin, vimentin, and fibronectin were upregulated. The EMT transforming factors (EMT-TF) TWIST/ZEB/SNAI1/SNAI2 were upregulated. Pharmaceuticals with the capacity to specifically target cytokines or their epithelial-mesenchymal transition (EMT) signalling pathways have the potential to significantly reduce treatment resistance, impede the progression of cancer, and prevent the recurrence of breast cancer. Epithelial-mesenchymal transition (EMT) induced by cytokines is a factor in breast cancer progression and metastasis.
Background:Breast cancer has emerged as the predominant malignant neoplasm globally, with potential implications for patient prognosis based on blood lipid profiles. This study aims to systematically review and meta-analyze the influence of lipid levels on the prognostic outcomes of individuals with breast cancer. Methods:A thorough search was performed across multiple academic databases, including Embase, Cochrane, PubMed, Web of Science, CNKI, and Wanfang Database, up to March 2024. A meta-analysis was conducted to assess the impact of total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) on the prognosis of Breast Cancer. The primary outcome measure was hazard ratios (HR) for overall survival (OS) and/or disease-free survival (DFS). Results:Eight studies meeting inclusion criteria from a total of 13,292 were included in the meta-analysis. The systematic review and meta-analysis demonstrate an association between lower HDL-C levels and poorer survival outcomes. However, the statistical analysis did not find significant associations between HDL-C, TG, and LDL-C levels and the prognosis of breast cancer patients. Conclusion:While our analysis reveals a link between reduced HDL-C levels and unfavorable survival outcomes, the statistical evidence does not support significant connections between HDL-C, TG, and LDL-C concentrations and the prognostic landscape for breast cancer patients. Further research is warranted to explore these relationships more comprehensively. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021297118.
Breast cancer (BC) represents a complex malignancy shaped by both genetic pre-disposition and environmental influences, with growing evidence implicating the gut micro-environment in its pathogenesis. While the therapeutic potential of gut-targeted interventions has gained attention, the precise molecular mechanisms remain poorly characterized. Tradi-tional Chinese medicine (TCM) has emerged as a valuable therapeutic approach due to its widespread availability and demonstrated clinical efficacy, particularly through its capacity to modulate gut homeostasis and exert systemic effects across multiple disease states, including breast cancer. Specific TCM formulations, including CCM, CMM, and MBC, have shown significant potential to reshape gut microbial composition, influence microbial metabolite pro-duction, restore immune homeostasis, enhance short-chain fatty acid biosynthesis, regulate estrogen metabolism, and induce beneficial epigenetic modifications, thereby offering a mul-tifaceted therapeutic strategy against breast cancer. This review systematically examines the pharmacological mechanisms, molecular targets, and clinical implications of TCM-based in-terventions in breast cancer management, highlighting their potential to open new avenues in oncological therapeutics.
Ethnopharmacological relevance: With the emergence of endocrine resistance, the survival and good prognosis of HR-positive breast cancer (HR + BC) patients are threatened. As a common complementary and alternative therapy in cancer treatment, traditional Chinese medicine (TCM) has been widely used, and its internal mechanisms have been increasingly explored. Aim of the review: In this review, the development status and achievements in understanding of the mechanisms related to the anti-invasion and anti-metastasis effects of TCM against HR + BC and the reversal of endocrine drug resistance by TCM in recent years have been summarized to provide ideas for antitumour research on the active components of TCM/natural medicine. Methods: We searched the electronic databases PubMed, Web of Science, and China National Knowledge Infrastructure database (CNKI) (from inception to July 2023) with the key words "HR-positive breast cancer" or "HRpositive breast carcinoma", "HR + BC" and "traditional Chinese medicine", "TCM", or "natural plant", "herb", etc., with the aim of elucidating the intrinsic mechanisms of traditional Chinese medicine and natural medicine in the treatment of HR + BC. Results: TCM/natural medicine monomers and formulas can regulate the expression of related genes and proteins through the PI3K/AKT, JAK2/STAT3, MAPK, Wnt and other signalling pathways, inhibit the proliferation and metastasis of HR + BC tumours, play a synergistic role in combination with endocrine drugs, and reverse endocrine drug resistance. Conclusion: The wide variety of TCM/natural medicine components makes the research and development of new methods of TCM for BC treatments more selective and innovative. Although progress has been made on research on TCM/natural medicine, there are still many problems in clinical and basic experimental designs, and more indepth scientific explorations and research are still needed.
BackgroundChemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN.MethodsWe searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI).ResultsWe conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them.ConclusionIce gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.
Triple negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. The absence of biomarker has given immune checkpoint inhibitors (ICIs) a broad prospect in this type of breast cancer. The infiltration of regulatory T cells (Tregs) expressing transcription factor forkhead box P3 (Foxp3) in the tumor microenvironment (TME) is the key factor leading to ICIs resistance. Therefore, elimination of tumor antigen-specific Tregs may be an important aspect of improving ICIs efficacy. In this study, it based on the Gene Expression Omnibus and The Cancer Genome Atlas database, along with in vivo and in vitro experimental models, to verified that the high expression of integrin-linked kinase (ILK) in TNBC is the key differential factor leading to the high infiltration of Foxp3+-Tregs in the TME. Then, we selected ILK-specific inhibitor, OSU-T315, to intervene in vitro and vivo. Importantly, we found that OSU-T315 blocked the secretion of CCL17/CCL22 in tumor cells by inhibiting the ILK/NF-κB pathway, resulting in the apoptosis of Foxp3+-Tregs and decreased programmed cell death-1 (PD-1) expression. Therefore, our findings indicate a novel mechanism of OSU-T315 with potential therapeutic application in TNBC.
ObjectiveTamoxifen is an effective anti-tumor medicine, but evidence has been provided on tamoxifen-related inflammation as well as its impact on gut microbiota. In this study, we aimed to investigate tamoxifen-induced gut microbiota and inflammation alteration.MethodsWe established a BC xenograft mouse model using the MCF-7 cell line. 16S rRNA gene sequencing was used to investigate gut microbiota. qRT–PCR, western blotting, and cytometric bead array were used to investigate inflammation-related biomarkers. Various bioinformatic approaches were used to analyze the data.ResultsSignificant differences in gut microbial composition, characteristic taxa, and microbiome phenotype prediction were observed between control, model, and tamoxifen-treated mice. Furthermore, protein expression of IL-6 and TLR5 was up-regulated in tamoxifen-treated mice, while the mRNA of Tlr5 and Il-6, as well as protein expression of IL-6 and TLR5 in the model group, were down-regulated in the colon. The concentration of IFN-γ, IL-6, and IL12P70 in serum was up-regulated in tamoxifen-treated mice. Moreover, correlation-based clustering analysis demonstrated that inflammation-negatively correlated taxa, including Lachnospiraceae-UCG-006 and Anaerotruncus, were enriched in the model group, while inflammation-positively correlated taxa, including Prevotellaceae_UCG_001 and Akkermansia, were enriched in the tamoxifen-treated group. Finally, colon histologic damage was observed in tamoxifen-treated mice.ConclusionTamoxifen treatment significantly altered gut microbiota and increased inflammation in the breast cancer xenograft mice model. This may be related to tamoxifen-induced intestinal epithelial barrier damage and TLR5 up-regulation.
[目的]采用网络药理学与生物信息预测分析并结合体内与分子实验验证百合抗焦虑抗抑郁的作用机制.[方法]采用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索百合抗焦虑抗抑郁的潜在活性成分;通过治疗靶点数据库(Therapeutic Target Database,TTD)检索活性成分抗焦虑抗抑郁的潜在作用靶标,构建成分与靶标网络;采用REACTOME与g:Profiler软件进行基因本体(gene ontology,GO)分析,京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)、REAC 和 WikiPathways 代谢通路(WikiPathways,WP)富集分析.以行为绝望抑郁悬尾和强迫游泳实验评价百合水提液抗抑郁活性,以酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测ICR小鼠海马内神经递质含量,以实时荧光定量聚合酶链式反应(Real-time polymerase chain reaction,Real-time PCR)分析抑郁小鼠脑内抑郁相关基因表达水平.[结果]百合通过β-谷甾醇、3-去甲基秋水仙碱与26-O-β-D-吡喃葡萄糖基-3β,26-二羟基胆甾烷-16,22-二氧基-3-0-α-L-鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷等5个潜在活性成分,可通过调控hsa-miR-203和hsa-miR-206等miRNAs与特异性蛋白 1(specificity protein 1,SP1)、RE1沉默转录因子(RE1 silencing transcription factor,REST)和CCCTC 结合因子(CCCTC-binding factor,CTCF)等转录因子的表达,进而共同调控蛋白激酶C epsilon型(protein kinase C epsilon,PRKCE)、γ-氨基丁酸 B 型受体亚基 2(gamma-aminobutyric acid type B receptor subunit 2,GABBR2)、γ-氨基丁酸 A 型受体亚基 p2(gamma-aminobutyric acid type A receptor subunit beta 2,GABRB2)和溶质载体家族6 成员 4(solute carrier family 6 member 4,SLC6A4)等基因的表达,可能最终影响了 γ-氨基丁酸通路、5-羟色胺通路、G蛋白偶联受体通路和单胺氧化酶通路等,增加抑郁小鼠脑内神经递质含量,发挥抗焦虑抗抑郁作用.[结论]采用网络药理学、生物信息预测以及实验验证百合抗焦虑抗抑郁的活性成分、潜在靶标和信号通路,为百合抗焦虑抗抑郁研究提供参考.
In recent years, there has been a significant increase in the incidence of Breast cancer (BC), making it the most common cancer among women and a major threat to women’s health. Consequently, there is an urgent need to discover new and effective strategies for treating BC. Ferroptosis, a novel form of cell death characterized by the accumulation of iron-dependent lipid reactive oxygen species, has emerged as a distinct regulatory pathway separate from necrosis, apoptosis, and autophagy. It is widely recognized as a crucial factor in the development and progression of cancer, offering a promising avenue for BC treatment. While significant progress has been made in understanding the mechanisms of ferroptosis in BC, drug development is still in its early stages. Numerous compounds, including phytochemicals derived from dietary sources and medicinal plants, as well as synthetic drugs (both clinically approved medications and laboratory reagents), have shown the ability to induce ferroptosis in BC cells, effectively inhibiting tumor growth. This comprehensive review aims to examine in detail the compounds that target ferroptosis in BC and elucidate their potential mechanisms of action. Additionally, the challenges associated with the clinical application of ferroptosis-inducing drugs are discussed, offering valuable insights for the development of novel treatment strategies for BC.
Aim We performed a systematic review and meta-analysis to evaluate the efficacy and safety of microwave ablation (MWA) for benign breast lesions. Material and methods PubMed, Embase, Web of Science, Cochrane Library databases, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform databases were searched. Results A total of 10 studies were included, giving a sample size of 1241 patients and 2729 benign breast lesions. The first complete ablation success rate was 96%. The volume reduction ratio (VRR) after 3/6/12 months was 47.4%, 62.1%, and 85.8%, respectively. After 12 months, the lesion disappearance rate was 53.6%, and the efficiency rate was 99%. The rate of excellent cosmesis was 88% and the rate of good cosmesis was 10%. The complication rate was 2%. Conclusions MWA is safe and effective for treating benign breast lesions. It can be a promising minimally invasive choice for benign breast lesions.
Abstract Background Ruai-sanyin formula (RASYF) is composed of a variety of anticancer herbs. It is widely used in the treatment of triple negative breast cancer (TNBC) and has proved to inhibit tumor growth and lung metastasis in animal models, but there is no evidence for clinical application in the real world. Methods We conducted this prospective cohort study at 5 research centers in China from November 2016 to December 2018. RASYF was set as an exposure factor. TNBC patients within 3 months after completion of standard adjuvant treatment were included. The exposed group received RASYF treatment, while the non-exposed group received observation. The primary end point was disease-free survival (DFS). Secondary end points included, overall survival (OS), distant disease-free survival (DDFS), relapse-free survival (RFS), QLQ-BR23 assesses quality of life in patients and adverse events. Results A total of 613 eligible patients with operable TNBC were enrolled, of which 588 were included in the Full Protocol Set. At a median follow-up of 48 months, DFS time was longer in those assigned to RASYF compared with observation (3-year DFS, 89.6% vs. 83.5%, [HR = 0.61, 95%CI (0.39-0.95)]; P = 0.03). Similar outcomes were observed for RFS (3-year RFS, 92.1% vs. 85.9%, HR = 0.55, [95% CI, 0.34-0.91]; P = 0.02). However, there was no statistically significant difference in OS and DDFS between the groups. In exploratory subgroup analysis, RASYF benefits were greater in patients with age under the 40 (3-year DFS, 88.4% vs. 76.1%, [HR = 0.45, 95%CI (0.21-0.95)]; P = 0.03). And RASYF is helpful to the improvement of postoperative quality of life. Comparing to the observation group, RASYF increased the mean CFB of BR23 scores in body image (12.34 vs. 8.76, P = 0.03),sexual function (11.79 vs. 9.23, P <0.01) , future perspective (9.90 vs. 6.53, P= 0.04), and decreased the scores of systemic therapy side effects (-12.41 vs. -9.24, P = 0.01). Safety analysis showed that RASYF caused major adverse reactions including impaired liver function (4.0%) and stomach pain (6.1%), but the overall security is controllable. Conclusion RASYF supplementation for 2 years after standard adjuvant chemoradiotherapy has certain clinical significance in preventing recurrence and metastasis and improving the quality of life of patients with early TNBC. Trial registration ClinicalTrials.gov: NCT03332368 Registered 6 November, 2017 (retrospectively registered)
Background:Androgen receptor (AR) is becoming an important factor in the pathogenesis of breast cancer. Traditional Chinese medicine (TCM) is widely used in treating breast cancer patients. Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which has worse prognosis than other subtypes. Herein, through this retrospective study, we summarize the therapeutic implications of AR and TCM in TNBC.Methods:The clinical and pathological data of TNBC patients who had undergone surgery at The First Affiliated Hospital of Zhejiang Chinese Medical University from 2017 to 2019 were collected and examined. The t-test, chi-square test, logistic regression model, and Kaplan-Meier survival estimates were used to analyze the data.Results:We identified 823 early breast cancer patients from January 2017 to December 2019, of whom 92 (11.2%) were pathologically confirmed to have TNBC. We excluded 5 patients according to the inclusion and exclusion criteria. In relation to the remaining 87 patients, 33 (37.9%) were AR positive. In the TNBC patients, positive AR expression was correlated with an older age (P=0.006), a higher weight (P=0.006), and lower Ki-67 expression (P=0.031). After a median follow-up time of 37 months (range, 24-60 months), 13 cases of relapse and metastasis (14.9%) were observed. We found that relapse and metastasis were correlated with being unmarried [P=0.004; hazard ratio (HR) =0.105; 95% confidence interval (95% CI): 0.023-0.487], nonporous (P=0.046; HR =0.209; 95% CI: 0.045-0.971), and negative AR expression (P=0.042; HR =1.223; 95% CI: 0.049-1.012). The AR-positive TNBC patients had better disease-free survival (DFS) than the AR-negative TNBC patients 2-5 years after surgery (P<0.05). TCM was an effective treatment for TNBC (P<0.001; HR =51.682; 95% CI: 6.660-401.025). In the AR-negative group, patients who received the TCM treatment tended to have a better DFS than those who did not receive the TCM treatment (P<0.001; HR =34.832; 95% CI: 4.448-272.756); however, no such difference was found in the AR-positive group.Conclusions:The TNBC patients with positive AR tended to have a low expression of Ki-67 and a better prognosis than AR negative TNBC patients. TCM is an effective treatment and has slight side effects.
Background An elevated level of olfactomedin-like-2A (OLFML2A) is unfavorable for female breast cancer patients. Patients with a high mRNA level of OLFML2A receive a poor prognosis. Therefore, we speculate that inhibiting the expression of this gene may be beneficial to breast cancer patients. We previously found that silencing the OLFML2A gene by using mRNA interference significantly inhibited proliferation and migration in triple-negative breast cancer (TNBC) cells. Methods Cell activity and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Celigo analyses. Cell migration and invasion were determined by wound-healing and transwell invasion assays. The mechanism of the inhibition of a small hairpin RNA that targets OLFML2A (shOLFML2A) was determined by using a GeneChip array, real-time quantitative PCR (RT-qPCR), and western blot analysis. Results Gene silencing by shOLFML2A induces apoptosis by promoting S phase arrest in TNBC cells. In addition, shOLFML2A decreased the progression of epithelial-mesenchymal transition (EMT). Additionally, microarray analysis showed that shOLFML2A significantly upregulated 428 genes and downregulated 712 genes. These significantly changed genes regulated DNA synthesis, chromosome alignment, microtubules and the cytoskeleton, cell movement, the cell cycle, cell necrosis, and apoptosis because they promoted G2/M DNA damage checkpoint regulation and p53 signaling, and because they inhibited integrin, hepatocyte growth factor (HGF), nerve growth Factor (NGF), and other tumor-promoting signaling pathways. Conclusions shOLFML2A reduces cell proliferation, migration, and invasion and promotes cell apoptosis. Therefore, the results of the present study suggest that OLFML2A is a potential therapeutic target for TNBC.
作为药食两用常见药材,大枣药用历史悠久,《伤寒论》等多部医书均有多处阐述,有补中益气与养血安神之功效[1].《中华医典》记载治疗抑郁方剂中,使用频次最高的十种复方约半数含大枣,如甘麦大枣、归脾汤、大枣汤与紫苏子汤等[2].研究表明,甘麦大枣汤等单用或联用可通过调节神经递质、下丘脑-垂体-肾上腺(HPA)轴及促进脑源性神经营养因子(BDNF)分泌等,有效治疗产后抑郁、乳腺癌合并抑郁以及中风后抑郁等[3].此外,大枣提取物可促进星形胶质细胞中BDNF表达水平,拮抗活性氧等自由基对神经细胞的损伤作用,这些证据表明大枣在抗抑郁具有潜在治疗作用[4].然而,大枣抗焦虑、抗抑郁的活性成分与作用机制并未得到揭示与阐明.因此,本文拟采用网络药理学,结合生物信息预测研究,探索大枣中抗焦虑、抗抑郁潜在的活性成分与分子机制.