Background Tiao-Shen-Zhi-Ai Formula (TSZAF) is a compound prescription of traditional Chinese medicine used clinically for the treatment of ovarian cancer. In this study, we selected three main active ingredients from TSZAF and combined them into a new TSZAF monomer combination (TSZAF mc) to investigate its effects and mechanisms on inhibiting ovarian cancer proliferation and inducing apoptosis. Methods The effects of TSZAF mc on proliferative activity and apoptosis in ovarian cancer HEY and SKOV3.IP1 cells were assessed in vitro using CCK-8 assay, colony formation assay, and apoptosis assay. Micromethods, flow cytometry, and immunofluorescence were employed to evaluate the impact of TSZAF mc on aerobic glycolytic metabolites and mitochondrial membrane potential. The mRNA and protein expression of key glycolytic genes were detected by quantitative real-time PCR (RT-PCR) and Western blot (WB). An ovarian cancer subcutaneous tumor model was established in NOD-SCID mice using SKOV3.IP1 cells. TSZAF mc was administered via continuous intraperitoneal injection, and its antitumor efficacy in vivo was assessed through anatomical observation, hematoxylin and eosin (H&E) staining, and immunohistochemistry (IHC). Further RT-PCR, WB, and IHC were performed to validate the expression of key upstream glycolytic genes at mRNA and protein levels. Drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) were used to confirm binding targets. Molecular docking was performed to predict the binding interactions between the monomers and AKT. Finally, the regulatory relationships within signaling pathways were elucidated based on functional assays. Results TSZAF mc effectively inhibited ovarian cancer proliferation and induced apoptosis. It reduced lactate and ATP production, downregulated mitochondrial membrane potential, and decreased the mRNA and protein expression of key glycolytic genes, including HK2, PKM2, PFKM, GLUT1, and LDHA. In vivo, TSZAF mc suppressed ovarian cancer growth. Moreover, TSZAF mc downregulated the expression of phosphorylated AKT (p-AKT) and phosphorylated FOXO3A (p-FOXO3A) at both protein and tissue levels. CETSA and DARTS demonstrated that TSZAF mc binds AKT. The AKT activator SC79 reversed the inhibitory effects of TSZAF mc on ovarian cancer proliferation and the downregulation of glycolytic proteins. Conclusion TSZAF mc inhibits ovarian cancer progression by regulating the AKT/ FOXO3A-mediated glycolysis pathway, which may represent one of the mechanisms underlying the clinical efficacy of TSZAF in ovarian cancer treatment.
Background: Psychoneurological symptom clusters (PNSCs) are common in patients with ovarian cancer and are associated with reduced quality of life, treatment interruption, and poor prognosis. However, effective interventions for PNSCs remain limited. Traditional Chinese medicine may provide comprehensive benefits for symptom management. Objective: This study aims to evaluate the efficacy and safety of the TiaoShenZhiAi (TSZA) regimen in alleviating PNSCs in patients with ovarian cancer and to assess its effects on quality of life and survival outcomes. Methods: A total of 316 patients with ovarian cancer aged 18 to 70 years with PNSCs will be included and randomly divided into 2 parallel groups. Both groups will receive standard treatment for ovarian cancer as the basic treatment. The intervention group will receive the TSZA regimen, that is, Compound Ciwujia Granules (containing Acanthopanax senticosus and Schisandra chinensis) combined with psychological intervention. The control group will receive a low-dose active control (simulated Compound Ciwujia Granules) combined with psychological intervention. The primary outcome is the remission rate of PNSCs at 3 months. The secondary outcome measures include the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 scale, the revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Quality of Life Scale, the traditional Chinese medicine syndrome scale, sleep quality, sleep diary, and the 1-year survival analysis. In addition, this study also includes a series of exploratory indicators (including functional magnetic resonance imaging, biomarkers of peripheral blood and tumor tissue, proportion of immune cells, cytokine levels, hypothalamic-pituitary-adrenal axis function, and immune gene expression analysis) and safety indicators (including vital signs, liver and kidney function, and electrocardiogram). The study outcomes will be evaluated based on different indicators during the treatment period (baseline and the 1st, 2nd, and 3rd mo of enrollment) and the follow-up period (the 6th, 9th, and 12th mo of enrollment). Data analysis will be conducted using R (version 4.5.3) software. A one-sided P value of <.03 will be considered statistically significant. Results: This study is designed to enroll a total of 316 participants. Participant enrollment is set to commence in October 2025, with no recruitment having occurred as of April 2026. The recruitment period will extend until September 2028 or until the target enrollment is met. Data analysis is scheduled for November 2028, with submission of the trial results to a peer-reviewed journal anticipated by May 2029. Conclusions: This study will evaluate the efficacy of the TSZA regimen in managing PNSCs in patients with ovarian cancer and generate clinical evidence for a new therapeutic option that improves quality of life and alleviates the symptom burden.
ObjectiveTo explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. MethodsA cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. ResultsThe prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. ConclusionDepression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.
Brain metastases (BM) from lung cancer remain a devastating complication that severely compromises patient survival. Its development is driven by dynamic and complex interactions between tumor cells and the central nervous system microenvironment, involving blood-brain barrier disruption, immunosuppressive niche formation, neural co-optation, metabolic adaptation, and peripheral immune dysregulation. Current strategies face intrinsic resistance and delivery barriers. This review aimed to systematically examine these mechanisms and therapeutic frontiers, including emerging interventions that preserve vascular-neural integrity, intercept neurotransmitter-mediated tumor support, reprogram brain resident cells, exploit metabolic vulnerabilities, and engineer advanced delivery systems, thereby proposing directions to overcome therapeutic challenges in lung cancer BM.
Background:Ovarian cancer (OC) is a highly fatal gynecologic malignancy with complex management challenges and limited long-term survival for advanced stages. Large language models (LLMs)-including systems such as GPT-4, Claude, Google Gemini, and others-are emerging artificial intelligence (AI) tools capable of performing health care-related tasks such as diagnostic support, treatment planning, report generation, and patient communication. However, their applications in OC care have not yet been comprehensively assessed. Objective:This protocol outlines a systematic review and meta-analysis aimed at evaluating the use, performance, and clinical impact of LLMs in OC management. We will examine how LLMs have been applied across various domains (eg, diagnosis, prognosis, treatment planning, and patient engagement), the metrics used to assess their performance (eg, accuracy, sensitivity, and area under the curve), and their strengths and limitations. Methods:This review will be conducted in accordance with PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines. A comprehensive search strategy will be implemented across biomedical, technical, and Chinese-language databases (eg, PubMed, Embase, Web of Science, IEEE Xplore, and China National Knowledge Infrastructure) from inception to December 31, 2025. Eligible studies include clinical evaluations, validation studies, and real-world implementation reports involving LLMs in OC care. Two independent reviewers will perform screening, data extraction, and quality appraisal using validated tools (eg, version 2 of the Cochrane risk-of-bias tool for randomized trials, Risk of Bias in Nonrandomized Studies of Interventions, Quality Assessment of Diagnostic Accuracy Studies 2, and Prediction Model Study Risk of Bias Assessment Tool+AI). Outcomes of interest include model performance metrics, clinical process impacts, safety concerns, and usability. Meta-analyses will be conducted where feasible using random-effects models in R (meta, metafor, and mada packages), including bivariate models for sensitivity and specificity. Results:The review is currently in progress. The PROSPERO registration has been completed, and the literature search and selection process is underway. Study selection, data extraction, and quality assessment are expected to be completed by mid-2026. Final results will include pooled performance metrics (eg, accuracy, F1-score, and area under the curve), qualitative insights into clinical integration, and identification of limitations such as reporting bias or insufficient external validation. Conclusions:This systematic review will provide the first comprehensive synthesis of evidence on the application of LLMs in OC care. It will identify promising use cases, highlight safety and reporting challenges, and inform future research directions. The findings are expected to support evidence-based integration of LLMs into gynecologic oncology workflows while promoting transparency and methodological rigor in AI evaluation.
Maimendong decoction (MMDD), a classic traditional Chinese medicine (TCM) formula prescribed for ‘lung atrophy’, has demonstrated efficacy against various pulmonary disorders. Our prior research confirmed that MMDD inhibit lung cancer metastasis by modulating natural killer (NK) cells. Paris polyphylla (P.P), a TCM herb with known anti-tumor properties, is often incorporated into classic formulas to enhance therapeutic outcomes. This study aimed to boost the anti-metastatic efficacy of MMDD against lung cancer by incorporating Paris polyphylla (Chonglou) and to investigate the underlying mechanisms. The Modified Maimendong Decoction (MMDD + P.P) Was Prepared by Adding 9–18 g of Paris polyphylla. Its Effects on the proliferation, migration, and Apoptosis of CTC-TJH-01 and LLC Cells Were Assessed Using CCK-8, Transwell, and Annexin V-FITC/PI Flow Cytometry assays. Apoptosis-related Proteins Were Analyzed by Western blot. A Tail Vein injection-induced Lung Metastasis Model in C57BL/6 Mice Was Established To Evaluate the Effects of MMDD + P.P, both Alone and in Combination with an anti-PD-1 antibody, on Metastasis Flow cytometry was used to profile T cell and NK cell populations in peripheral blood. Histological and molecular analyses of metastatic tissues were performed using H E staining, immunohistochemistry (for Ki-67 and cleaved caspase-3), and immunofluorescence (for CD8+ T cell and NK cell infiltration). Compared to MMDD alone, MMDD + P.P (18 g) significantly inhibited proliferation and migration, and induced apoptosis in both CTC-TJH-01 and LLC cells. These effects were associated with the upregulation of pro-apoptotic proteins (cleaved caspase-3, BAX, cleaved PARP) and downregulation of anti-apoptotic proteins (BCL-2, Survivin). In vivo, while both MMDD and MMDD + P.P reduced the number of lung metastatic nodules, MMDD + P.P (18 g) was uniquely effective in significantly reducing overall tumor burden, which correlated with decreased Ki-67 and increased cleaved caspase-3 in metastatic foci. Furthermore, MMDD + P.P (18 g) significantly increased the proportions and tumor-infiltration of NK cells and CD8+ T cells. It also synergized with anti-PD-1 therapy, enhancing its anti-metastatic effect and boosting the expression of cytotoxic markers (CD107a, perforin, granzyme B) and TNF-α in CD8+ T cells. Incorporating Paris polyphylla into MMDD enhances its anti-metastatic efficacy through a dual mechanism: directly inducing apoptosis in lung cancer cells and amplifying anti-tumor immunity by increasing the abundance and cytotoxic function of CD8+ T cells. The synergy between MMDD + P.P and anti-PD-1 antibody therapy highlights the potential of this modified TCM formula as a promising adjunctive treatment for inhibiting lung cancer metastasis. ∙Modified Maimendong Decoction Plus Paris polyphylla (MMDD + P.P) exhibits enhanced in vitro anti-lung cancer activity compared to the original MMDD, with superior inhibition of proliferation, migration, and induction of apoptosis. ∙MMDD + P.P demonstrates superior in vivo anti-metastatic efficacy against lung cancer relative to the original MMDD. ∙MMDD + P.P exerts immunomodulatory effects on CD8+ T cells, enhancing their anti-tumor activity. ∙MMDD + P.P potentiates the anti-metastatic efficacy of PD-1 monoclonal antibody therapy in lung cancer.
Organ damage from cancer treatment remarkably effects patients’ prognosis and quality of life. In recent years, preventive organ protection strategies, such as interdisciplinary collaboration, early prevention, precision interventions, psychological support, and the integrated application of traditional Chinese medicine, have demonstrated substantial clinical value and achieved notable progress. However, these approaches still encounter multiple challenges. Establishing multidisciplinary teams, optimizing therapeutic balance, and strengthening evidence-based research are essential for addressing the challenges related to treatment balance optimization, multidisciplinary coordination, and clinical translation of novel technologies. This review systematically summarizes recent advancements in preventive organ protection, analyzes existing challenges and potential solutions, and offers forward-looking recommendations. It aims to provide valuable insights for optimizing comprehensive cancer treatment strategies and improving long-term patient outcomes.
BackgroundMetastasis is the primary cause of poor prognosis and high mortality in lung cancer. Surgery with postoperative adjuvant chemotherapy is the standard treatment for patients with stage IIA-IIIA lung cancer with negative driver genes. However, recurrence rates remain significant. In China, traditional Chinese medicine shows potential as an adjuvant therapy to reduce treatment toxicity and improve clinical efficacy. ObjectiveThis study aimed to evaluate its efficacy and safety in preventing postoperative metastasis in driver gene-negative stage IIA-IIIA lung cancer, based on the promising preclinical results of Fuzheng Quxie Formula against lung cancer metastasis. In this trial, we hypothesize that the treatment group will have better efficacy and safety than the control group. MethodsA multicenter, double-blind, randomized, placebo-controlled parallel group trial will be conducted. Eligible patients will be randomized into a treatment group (daily Fuzheng Quxie Formula granules+regular chemotherapy) and a control group (daily Chinese medicine placebo granules+regular chemotherapy) in a ratio of 1:1. Fuzheng Quxie Formula will be administered orally, twice a day, in the morning and evening, for 6 months. Patients will be followed up after the end of treatment for 18 months. After the end of the program, follow-up will be continued for 5 years or until the patient dies (or progressed). The primary efficacy endpoint is disease-free survival, and the secondary efficacy endpoints are overall survival, minimal residual disease, circulating tumor cells, Chinese medicine symptom score, quality-of-life assessment, immune indicators, tumor markers, peripheral blood systemic immune-inflammation index, and prognostic nutritional index. We will conduct per-protocol analyses on these outcomes. In addition, we will also evaluate the safety of the Fuzheng Quxie Formula. ResultsThis study began screening and recruitment in March 2023. Recruitment is ongoing; by the end of 2024, a total of 180 eligible participants will be enrolled. Recruitment will continue until the end of June 2025 or until the target sample is reached. We estimate that the results will be published by March 2026. ConclusionsThis study is a high-quality, large-scale, multicenter, double-blind, randomized controlled trial. This will be the first trial to evaluate the efficacy and safety of Fuzheng Quxie Formula in inhibiting metastasis after surgery in stage IIA-IIIA lung cancer with negative driver genes. Provide a basis for the clinical application of Fuzheng Quxie Formula. Trial RegistrationClinicalTrials.gov NCT06381960; https://clinicaltrials.gov/study/NCT06381960 International Registered Report Identifier (IRRID)DERR1-10.2196/66342
BACKGROUND: Circulating tumor cells (CTCs) serve as the “seeds” of tumor metastasis, and the clustering of CTCs is critically associated with tumor metastasis and the mortality of lung cancer patients. Inhibiting the survival of CTC clusters represents a pivotal strategy for anti-lung cancer metastasis therapy. This study is designed to explore the impact and underlying mechanism of lung cancer CTC clusters in mediating resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), thereby offering novel insights into anti-lung cancer metastasis treatment. METHODS: Using the human lung adenocarcinoma CTC line CTC-TJH-01, we performed transcriptome analysis to identify differentially expressed genes. CCK-8, LDH, Calcein AM/EthD-1, and Annexin V-FITC/caspase-3 assays evaluated the effects of osimertinib, Tivantinib, or their combination on CTC-TJH-01 and A549 cell proliferation and apoptosis. RT-qPCR, western blot, and immunohistochemistry analyzed gene and protein expression. A lung metastasis mouse model was established by injecting CTC-TJH-01 clusters, with anatomical observation and H&E staining for evaluation. RESULTS: Our study demonstrated that CTC-TJH-01, A549, and H1975 cell clusters in suspension exhibited higher resistance to osimertinib compared to their adherent counterparts. Notably, the expression of the HGF gene was remarkably upregulated in CTC-TJH-01 cell clusters. Activation of the HGF/c-MET pathway was observed in CTC clusters, accompanied by a concurrent downregulation of EGFR protein expression. Significantly, the c-MET inhibitor Tivantinib, but not the HGF inhibitor SRI, effectively suppressed the survival of CTC-TJH-01 and A549 cell clusters. Moreover, Tivantinib, either as a single-agent or in combination with osimertinib, exerted a potent inhibitory effect on the in vivo metastasis of CTC-TJH-01 cell clusters. CONCLUSION: These findings indicate that CTC clusters contribute to resistance against EGFR-TKI treatment, and c-MET inhibitors hold promise as potential therapeutic agents for targeting CTC cluster survival to impede lung cancer metastasis.
Metastasis is a key cause of death in tumor patients,and a number of tumor patients have comorbid psychosomatic abnormalities and are in a state of chronic stress.Chronic stress affects the release of many kinds of hormones and neurotransmitters,such as epinephrine,norepinephrine,dopamine,glucocorticoids,cortisol,sex hormones,etc.,through the hypothalamus-pituitary-adrenal axis and sympathetic nervous system.These substances can act on the β-adrenergic receptor,glucocorticoid receptor,etc.,on tumor cells,immune cells,and other cells in the tumor microenvironment and promote the tumor progression and metastasis by directly enhancing the invasive and metastatic ability of tumor cells,inducing the formation of the immunosuppressive microenvironment and promoting tumor angiogenesis and other pathways.Antip-sychotic drugs,β-blockers,and glucocorticoid receptor antagonists have inhibitory effects on chronic stress-mediated tumor metastasis and have achieved certain clinical efficacy.Relevant studies have been carried out on traditional Chinese medicine decoctions and monomers,which can inhibit tumor metastasis by modulating the immune microenvironment and reversing chronic stress-mediated hormonal changes.The psychological problems of tumor patients have gradually received attention,and the development of new anti-metastatic drugs based on the mechanism of action of chronic stress in promoting tumor progression and metastasis provides new ideas for the improvement of the overall efficiency of tumor prevention and treatment.
Symptom clusters are closely related to the decline in patients’ quality of life, increased risk of treatment interruption and poor prognosis. Among patients with ovarian cancer, the manifestation of psychoneurological symptom clusters are particularly prominent, seriously affecting their quality of life and prognosis of the disease. Efficient intervention measures are urgently needed. However, there is still a lack of specific treatment methods for the psychoneurological symptom clusters of ovarian cancer at present. Traditional Chinese medicine shows great potential in improving tumor-related symptom clusters and has unique advantages in overall regulation and comprehensive intervention. The primary objective of this study is to evaluate the efficacy and safety of the TSZA regimen in alleviating mental and psychological symptoms among ovarian cancer patients. Secondary objectives include assessing its impact on patients’ quality of life and survival outcomes. Furthermore, the study aims to explore the characteristics of the patient population that derives benefit from the TSZA regimen for these symptoms. A total of 316 ovarian cancer patients aged 18 to 70 with psychoneurological symptom cluster will be included and randomly divided into two parallel groups. Both groups will receive standard treatment for ovarian cancer as the basic treatment. The experimental group will receive the TSZA regimen, that is, Compound Ciwujia Granules (containing Acanthopanax senticosus and Schisandra chinensis) combined with psychological intervention. The control group will receive placebo combined with psychological intervention. The primary outcome measure is the psychoneurological symptom cluster score. Secondary outcome measures included the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire -9 (PHQ-9), the Generalized Anxiety Disorder -7 (GAD-7) scale, the revised Piper Fatigue Scale, the EORTC QLQ-C30 Quality of Life Scale, the TCM Syndrome Scale, and the 1-year survival analysis. In addition, this study also set a series of exploratory indicators (including sleep diary, functional magnetic resonance imaging, biomarkers of peripheral blood and tumor tissue, proportion of immune cells, cytokine levels, HPA axis function and immune gene expression analysis) and safety indicators (including vital signs, liver and kidney function and electrocardiogram). The study will be evaluated based on different indicators during the treatment period (baseline and the 1st, 2nd, and 3rd months of enrollment) and the follow-up period (the 6th, 9th, and 12th months of enrollment). Data analysis will be conducted using SPSS 26 software. A p value <0.05 is considered statistically significant. This study is designed to enroll a total of 316 participants. Participant enrollment is set to commence in October 2025, with no recruitment having occurred as of November 2025. The recruitment period will extend until September 2028 or until the target enrollment is met. Data analysis is scheduled for November 2028, with submission of the trial results to a peer-reviewed journal anticipated by May 2029. This study will evaluate the efficacy of the TSZA regimen in managing psychoneurological symptom clusters in ovarian cancer patients, and generate clinical evidence for a new therapeutic option that improves quality of life and alleviates the symptom burden. ClinicalTrials.gov NCT07050563; https://clinicaltrials.gov/study/NCT07050563
Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
BACKGROUND:Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm that usually originates from liver cells and is one of the most common malignancies worldwide. To improve the survival rate of HCC patients, specific prognostic markers are essential to guide HCC therapy. CEP55 is a microtubule-bundling protein involved in critical cell functions, including cell growth, transformation, and cytokinesis. AIMS:This study examined gene alterations in HCC tumor tissues through comprehensive analysis, aiming to elucidate their contribution to disease development. METHODS:Bioinformatics tools were employed to investigate the expression, genetic variations, prognostic significance, and clinicopathological relevance of CEP55 across GEO and TCGA datasets. We further explored gene alterations, DNA methylation levels, and immune infiltration of CEP55. To elucidate the potential molecular mechanisms involved, GO and KEGG analysis was performed. Finally, RT-qPCR was also performed on a number of normal and tumoral cell lines in vitro, which demonstrated that the expression of the CEP55 was significantly higher in the tumor cell lines. RESULTS:We observed that CEP55 was upregulated in 16 cancers compared to corresponding normal tissues. CEP55 was found to be related to T stages, pathologic stages, histologic grade, and levels of AFP. K-M analysis demonstrated that CEP55 expression was associated with a worse outcome. ROC curve analysis showed that CEP55 expression accurately distinguished HCC from normal tissue (AUC = 0.954). The area under 1-,3- and 5-year survival ROCs were above 0.6. The HSPA4 genetic alterations in HCC were 0.8%. Among the 15 DNA methylation CpG sites, 6 were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints in HCC. The KEGG pathway analysis indicated that CEP55 was associated with the cell cycle and presented together with CDK1. HCC cell lines were demonstrated to express high levels of CEP55 compared to normal cells. CONCLUSION:As a result of bioinformatic analyses and RT-qPCR validation in HCC, CEP55 increased in HCC tissues and was associated with the stage of the disease and survival rate.
The emergence of Poly (ADP -ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of ROR alpha , thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3 beta signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.
Glycolysis is one of the key metabolic reprogramming characteristics of ovarian cancer. Ursolic Acid (UA), as a natural compound, exerts a beneficial regulatory effect on tumor metabolism. In this study, we have confirmed through RNA-seq analysis and a series of in vitro and in vivo functional experiments that UA significantly inhibits ovarian cancer cell proliferation, promotes tumor apoptosis, and reduces glycolysis levels. Additionally, it demonstrates synergistic therapeutic effects with cisplatin in both in vitro and in vivo experiments. Furthermore, at the molecular level, we found that UA inhibits glycolysis in ovarian cancer by binding to the transcription factor KLF5 and blocking the transcriptional expression of the downstream PI3K/AKT signaling pathway, thereby exerting its therapeutic effect. In conclusion, our research indicates that UA can inhibit the proliferation, apoptosis, and glycolysis levels of ovarian cancer cells through the KLF5/PI3K/AKT signaling axis. Our findings offer a new perspective on the therapeutic application of the natural compound UA in ovarian cancer and support its potential development as a candidate for chemotherapy.
肿瘤与抑郁是严重困扰人类的两大类疾病,临床上肿瘤和抑郁常相伴发生,两者存在复杂的相互促进关系,二者共病造成了巨大的社会和经济负担,但目前尚缺乏系统的肿瘤抑郁共病研究平台.田建辉"调神治癌"课题组通过联合上海市精神卫生中心开展肿瘤相关精神心理问题的临床与基础研究探索,成功构建了"调神治癌"的临床和基础实验综合研究平台,以期通过专业详实的研究,丰富心理社会肿瘤学科内容,从神经-内分泌-免疫环路系统探索肿瘤防治的"生物-心理-社会"医学模式.
肿瘤患者逐年增多,对癌症患者进行综合照料管理,以期延长生存期、提高生活质量,仍属待发展领域.研究发现肿瘤患者有较高的焦虑、抑郁等精神心理异常发病率,且直接影响患者的治疗和预后.笔者从肿瘤相关性焦虑、抑郁等精神心理异常的基础研究进展与临床治疗等方面进行综述,以期采取有效措施积极干预肿瘤患者的心理问题,提高我国肿瘤患者综合治疗的疗效.
卵巢癌作为妇科常见的恶性肿瘤,目前其总体疗效还有待提高,配合中医药的综合治疗有助于提升卵巢癌综合治疗疗效,此文介绍1 例中西医结合内外兼治晚期卵巢癌伴颈部淋巴结、乳腺转移患者验案,由于转移部位的特殊,中医药的运用很好地改善了患者的相关症状,帮助肿块退缩创面的愈合,改善了化疗相关不良反应,同时协同抗肿瘤,帮助耐受性较好的患者完成病因治疗,病灶退缩,创面愈合,大大提升了其生活质量.中医药对于卵巢癌的治疗多靶点,全方位已经成为目前肿瘤综合治疗不可或缺的一部分.
Ovarian cancer,with the highest mortality among gynecological malignancies,poses a serious threat to the health and safety of women.In recent years,it has become more and more prominent in the treatment of ovarian cancer with traditional Chinese medicine(TCM),and abundant data in modern pharmacological studies have supported the effectiveness and feasibility.By explo-ring the relevant descriptions of ovarian cancer in ancient TCM literature,this paper summarized the core pathogenesis of ovarian cancer,and discussed the clinical application of TCM in perioperative period,chemotherapy and follow-up maintenance treatment of ovarian cancer,aiming to improve the comprehensive curative effect of patients with ovarian cancer and break through the bottleneck of clinical prognosis of the disease.
目的:构建血道转移模型,从神经-内分泌-免疫学角度探讨调"神"预防肺癌转移的作用及机制.方法:采用巨猫牌R3H仓鼠饲养笼(84 cm×48.5 cm×45 cm),辅以跑步轮、隧道、木制玩具、小木屋和筑巢材料,构建小鼠富集饲养环境;以普通饲养笼作为小鼠标准饲养环境进行对照.采用小鼠Lewis肺癌细胞在C57BL/6小鼠上分别建立皮下移植瘤模型和尾静脉注射肺转移模型,观察不同饲养环境对荷瘤小鼠肿瘤生长、肺转移和小鼠生存期的影响;采用流式细胞术检测小鼠外周血中的免疫细胞水平;采用ELISA检测小鼠血清中肾上腺素和去甲肾上腺素水平;采用HE染色和免疫组化技术检测小鼠肺脏病理情况及转移前微环境相关指标.结果:富集环境组荷瘤小鼠的肿瘤大小、瘤重、肺转移灶数目等均显著低于标准环境组(P<0.05,P<0.01),且富集环境组小鼠生存期显著长于标准环境组(P<0.01).两组小鼠之间脾脏指数及胸腺指数无显著差异.小鼠外周血中的髓源性抑制细胞(MDSCs)比例在标准环境组中显著升高(P<0.01);而CD4+T细胞、CD8+T细胞、NK、Tregs、肾上腺素和去甲肾上腺素水平在两组之间无显著差异.小鼠肺脏免疫组化结果显示富集环境组S100A9的表达水平明显高于标准环境组(P<0.05);而CD3+T细胞、CD4+T细胞、S100A8、MMP9的表达无明显差异.结论:引入富集环境模型,模拟临床调"神"干预,可通过降低小鼠外周血中MDSCs水平,干预免疫逃逸的发生,从而达到抑制荷瘤小鼠肿瘤生长和肺转移,以及延长小鼠生存期的作用.