Background:Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality. Immunotherapy benefits only a subset of patients, highlighting the need to explore immune-related signatures associated with response. Materials and methods:We analyzed a single-cell RNA sequencing dataset of 27,414 cells from tumor core, edge, and matched normal mucosa to investigate NKT cell heterogeneity. A spatial transcriptomics dataset characterized interactions between NKT and Th1 cells in CRC tissues. Integrating nine CRC cohorts from TCGA and GEO, we assessed associations between NKT cell infiltration and clinical outcomes. NKT and Th1 cell-related genes (NTRG) were identified and integrated into an NTRG score, which was systematically validated across multiple independent CRC cohorts to characterize its associations with survival and immunotherapy response. In addition to multi-database validation using several external transcriptomic datasets, we analyzed somatic mutation profiles, GO enrichment, and drug sensitivity patterns associated with different NTRG score groups. Furthermore, key NTRG genes were biologically validated in clinical CRC tissue specimens using immunohistochemistry. Results:Elevated NKT cell infiltration correlated with improved prognosis and enhanced immunotherapy sensitivity. Spatial analysis revealed NKT and Th1 co-localization mediated by COLLAGEN signaling. The NTRG score quantified tumor-immune properties, and high scores were linked with worse overall survival yet stronger immunotherapy response. Validation confirmed differential NTRG expression between normal and cancerous tissues and across immunotherapy responders and non-responders. Conclusion:NTRG is an exploratory multi-gene signature associated with the immune landscape of colorectal cancer, offering a foundation for future investigation into its relationship with immunotherapy response and tumor microenvironmental organization.

Background:Immunotherapy has revolutionized cancer treatment. However, its clinical application remains limited. There is an urgent need for new predictive and prognostic biomarkers that can identify more patients with objective and durable responses and thus, improve the accuracy of prognosis. Methods:A predictive model for immunotherapy was developed using 34 single-cell RNA sequencing (scRNA-Seq) datasets from various cancer types and eight bulk RNA-Seq datasets from immune checkpoint inhibitor (ICI) cohorts. Seven machine learning (ML) methods were applied to identify vital genes associated with both cancer and immune characteristics. Differentially expressed genes (DEGs) were validated using RT-PCR and immunohistochemical (IHC) analyses of clinical samples. Results:Analysis of scRNA-seq datasets and autonomic nervous system development (ANSD) scores revealed 20 genes comprising a novel ANSD-related differential signature (ANSDR.Sig). A pan-cancer predictive model for ICI prognosis based on ANSDR.Sig was constructed, with the random forest algorithm yielding the most robust performance. Further screening using five ML methods on the ICI RNA-seq datasets identified 18 key genes, forming the Hub-ANSDR.Sig. Regulatory network analysis revealed diversified molecular interactions between Hub-ANSDR.Sig genes, transcription factors, and miRNAs. Hub-ANSDR.Sig was strongly associated with immune cell infiltration, microsatellite instability (MSI), and overall survival (OS) across various cancer types. In gastric cancer (GC), its role in immune dysfunction, tumor mutational burden (TMB), MSI, mutation frequency, immune infiltration, cell-cell communication, and developmental trajectories was confirmed. Moreover, several Hub-ANSDR.Sig genes were differentially expressed in GC compared to normal tissue and were enriched in immunotherapy-sensitive GC samples relative to resistant ones. Conclusion:Our results offer novel insights into predicting immunotherapy efficacy using ANSD-related signature, with the goal of improving clinical strategies and expanding potential indications. This approach also aims to develop more accurate prediction models and therapeutic interventions, thereby helping more patients benefit from immunotherapy.

PURPOSE:Many cancer patients express interest in using herbal medicine during chemotherapy, but little is known about its benefits and risks. This study aimed to evaluate the effects of the Chinese herbal medicine JianPi-BuShen formula (JPBS) on adjuvant chemotherapy completion in colon cancer patients. PATIENTS AND METHODS:This multi-center, phase III, randomized, placebo-controlled trial included patients with stage II (high risk for recurrence) and stage III colon cancer following surgery, planning to receive CAPOX (capecitabine and oxaliplatin) chemotherapy. Patients were randomized 1:1 to receive either JPBS or a placebo. The primary outcome was the completion rate of planned chemotherapy cycles. Secondary outcomes included relative dose intensity (RDI), chemotherapy-induced toxicities, quality of life (measured by the Edmonton Symptom Assessment System - ESAS), adverse events (AEs), and serious AEs (SAEs). Predefined subgroup analyses were performed by age (>65/≤65) and TNM stage (II/III). RESULTS:A total of 376 participants were analyzed, with a median age of 60.3 years; 56.9 % were male, and 67.6 % had stage III disease. Chemotherapy completion was significantly higher in the JPBS group than in the placebo group (63.0 % vs. 47.6 %, P = 0.003). Oxaliplatin RDI was also higher in the JPBS group (P = 0.049). Subgroup analyses showed JPBS significantly improved completion rates for stage II patients (73.0 % vs. 42.4 %, P = 0.001) and younger patients (66.9 % vs. 48.8 %, P = 0.004). JPBS reduced grade ≥ 2 vomiting (3.8 % vs. 6.4 %, P = 0.007) but increased grade ≥ 2 thrombocytopenia (16.2 % vs. 12.4 %, P = 0.012). Quality of life improved in stage II and younger patients. CONCLUSION:JPBS improved chemotherapy completion rates in stage II and younger colon cancer patients without compromising tolerability. Further research is needed to explore its mechanisms and long-term effects.

Ethnopharmacological relevance: Complementary treatment with valuable efficacy and less toxic or side effect is in urgent need for colorectal cancer (CRC) therapy. Yiqi Huayu Jiedu Decoction (YHJD) is a polyherbal formulation which has been applied in clinic to treat CRC for a long period of time. Nevertheless, the potential active ingredients and molecular mechanism remains to be further explored.Aim of the study: To probe the effective compounds of YHJD and its underlying pharmacological effects. Moreover, the influence on liver metastasis of CRC as well as function of natural killer (NK) cells results from YHJD was investigated.Materials and methods: The active ingredients and target genes of YHJD was examined through TCMSP databases. Compound-compound target network was performed by applying Cytoscape3.9.1 software. The CRC-related disease targets were explored via DisGeNET database. Venn database was used to find the common genes between CRC and YHJD. Protein-protein interaction network was established by STRING database. Biological process and signaling pathways potentially regulated by YHJD were evaluated by DAVID database. Western blot assay was then conducted to further investigate the effect of YHJD on PI3K-AKT signaling. The association between NK cells content and TNM or pathological stages of CRC was studied through TCGA database. The killing efficiency of NK cells was researched by CCK8 experiment. In vivo assay and HE staining were performed to assess the anti-liver metastasis effect of YHJD. The variation of NK cells content was authenticated by applying flow cytometry analysis.Results: We firstly found 176 active ingredients and 268 target genes of YHJD. Compound-compound target network was then established consisted of 455 nodes and 3989 edges. Then 707 disease targets associated with CRC were discovered and 42 common genes between CRC and YHJD were identified. Protein-protein interaction network was further constructed, among which 5 vital genes including TP53, AKT1, TNF, MYC and CCND1 were recognized. GO and KEGG analysis was performed to explore probable biological process and signaling pathways regulated by YHJD. Particularly, the ratio of p-PI3K/PI3K and p-AKT/AKT at protein level representing the activation of PI3K-AKT signaling could be suppressed by YHJD. In addition, bioinformatic analysis detected reduced NK cells content in CRC tissues, which gave rise to more advanced node, metastasis and pathological stages. We next presented that YHJD can improve the killing effect of NK cells on CRC. At meantime, YHJD was capable of suppressing liver metastasis of CRC in vivo as well as promoting the content of NK cells, while the improving effect was partially neutralized by anti-ASGM1.Conclusions: Our research indicates that YHJD can prohibit liver metastasis of CRC in vivo. The therapeutic effectiveness is linked to regulation of multiple targets and effector process, especially PI3K-AKT signaling as well as immune response dominated by NK cells.

Ethnopharmacological relevance: Sargentodoxa cuneata (Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson, DXT)-Patrinia villosa(Patrinia villosa (Thunb.) Dufr, BJC) constitutes a commonly employed herb pair in Chinese medicine for colorectal cancer (CRC) treatment. Modern pharmacological investigations have revealed the anticancer activities of both Sargentodoxa cuneata and Patrinia villosa. Nevertheless, comprehensive studies are required to discern the specific antitumor active ingredients and mechanism of action when these two herbs are used in combination.Aim of the study: Through the integration of network pharmacology, molecular docking techniques, experimental assays, and bioinformatics analysis, our study aims to forecast the active ingredients, potential targets, and molecular mechanisms underlying the therapeutic efficacy of this herb pair against CRC. Materials and methods: Plant names (1, Sargentodoxa cuneata (Oliv.) Rehder & E.H.Wilson; 2, Patrinia villosa (Thunb.) Dufr.) have been verified through WorldFloraOnline (www.worldFloraonline.org) and MPNs (http://mpns.kew.org). The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Plat-form (TCMSP) were utilized for screening the active ingredients of the herb pair. The PharmMapper database was employed to predict the target proteins for each active ingredient. CRC-related targets were obtained from the Genecards database, Online Mendelian Inheritance in Man (OMIM) database, Disease Gene Network (DisGeNET) database, and Therapeutic Target Database (TTD). Common targets were identified by intersecting the target proteins of all active ingredients with CRC-related targets. Protein-protein interactions (PPI) for the common target proteins were constructed using the String database and Cytoscape 3.9.1 software. Network topology analysis facilitated the identification of core targets. These core targets were subjected to enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Metascape database. Molecular docking was performed using Discovery Studio 2019 to investigate the interactions between the active ingredients and core target proteins. The core targets were validated through bioinformatics analysis using GEPIA, HPA, and the cBioPortal database. Finally, a series of experiments were conducted to further validate the results in vitro.Result: A total of 15 active ingredients and 255 herb targets were identified, resulting in 66 common targets in conjunction with 6113 disease targets. The PPI analysis highlighted AKT1, EGFR, CASP3, SRC, and ESR1 as core targets. KEGG enrichment analysis indicated significant enrichment in the PI3K-AKT signaling pathway, a pathway associated with cancer. Molecular docking experiments confirmed favorable interactions between dihydroguaiaretic acid and the core target proteins (AKT1, EGFR, CASP3, and ESR1). Bioinformatics analysis revealed differential expression of EGFR and CASP3 in normal and CRC tissues. Cellular experiments further verified that dihydroguaiaretic acid induces apoptosis in colorectal cancer cells through the PI3K-AKT signaling pathway.Conclusion: Our network pharmacology study has elucidated that the Sargentodoxa cuneata-Patrinia villosa herb pair exerts the negative regulation of the PI3K/AKT/mTOR signaling pathway, ultimately leading to the induction of apoptosis in colorectal cancer cells. This research has predicted and validated the active ingredients, potential targets, and molecular mechanisms of Sargentodoxa cuneata-Patrinia villosa in the treatment of CRC, providing scientific evidence for the use of traditional Chinese medicine in managing CRC.

BACKGROUND:Neoadjuvant chemotherapy (NAC) is a frequently intervention for patients with locally advanced gastric cancer (GC). Nevertheless, its impact on the tumor immune microenvironment remains unclear.METHODS:We used immunohistochemistry to identify T-cell subpopulations, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) in the GC microenvironment (GCME) among paired samples (pre-chemotherapy and post-chemotherapy) from 48 NAC-treated patients. Multiplex immunofluorescence (mIF) was performed to assess immune biomarkers, including CK, CD4, CD8, FOXP3, PD1, PD-L1, CD163, CD86, myeloperoxidase and Arginase-1 in paired samples from 6 GC patients whose response to NAC were rigorously defined.RESULTS:NAC was intricately linked to enhanced CD8+:CD4+ ratio, reduced CD163+ M2-like macrophages, augmented CD86+ M1: CD163+ M2-like macrophage ratio, and diminished FOXP3+ regulatory T cells (T-regs) and TANs density. Based on mIF, PD1+CD8+T-cells, FOXP3+T-regs, PD-L1+ TANs, and CD163+ M2-like macrophages exhibited marked reduction and greater co-localization with tumor cells following NAC. The pre-NAC FOXP3+ T-regs and CD163+ M2-like macrophages content was substantially elevated in the response cohort, whereas, the post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were intricately linked to the tumor pathologic response. We observed greater CD163+ M2-like macrophages and tumor cells co-localization following NAC, which was correlated with tumor pathologic response. Lastly, multivariate analysis revealed that post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were stand-alone indicators of positive patient prognosis.CONCLUSIONS:NAC converts the GCME to an anti-tumorigenic state that is conducive to enhanced patient outcome. These finding can significantly benefit the future planning of highly efficacious and personalized GC immunotherapy.

Objective: To investigate the relationship between miR-27a-3p/RCBTB1/β-catenin and the clinical characteristics of gastric cancer, and to explore the mechanism of Yiqi Huayu Jidu Decoction inhibiting epithelial mesenchymal trasformation（EMT）. Methods: The expression and clinical significance of miR-27a-3p and RCBTB1 in gastric cancer was analyzed by bioinformatics. High-throughput sequencing was used to detect the difference of mRNA expression in liver metastatic tumor tissues of mice. Stable cell lines with silenced or overexpressed miR-27a-3p or RCBTB1 were constructed by plasmid transfection. The invasion and migration ability of gastric cancer cells was Detected by Transwell and Wound-healing assays.MFC cells were injected into the spleen to establish liver metastasis model of gastric cancer in mice, and Yiqi Huayu Jiedu Decoction was used for intervention. The number of liver metastases was detected, and the liver infiltration of gastric cancer cells was detected by HE staining. Expression of miR-27a-3p, RCBTB1, β-catenin, E-cadherin and Snail were detected by RT-PCR and Western Blot. Results: The expression of miR-27a-3p was higher in gastric cancer than normal tissues（P＜0.01）, mir-27a-3p expression in stage Ⅳ gastric cancer was higher than that in stageⅠ,Ⅱ and Ⅲ（P＜0.05）. Compared with the control group, the invasion and migration of gastric cancer cells in miR-27a-3p overexpression group was enhanced, while it got weakened in miR-27a-3p silencing group（P＜0.01）. High-throughput sequencing showed that RCBTB1 in the liver metastatic tumor tissues of mice in Yiqi Huayu Jiedu Decoction group was higher than that in the control group, and TargetScan predicted that RCBTB1 was a potential target gene of miR-27a-3p. Compared with control group, overexpression of miR-27a-3p inhibited RCBTB1（P＜0.01）,while silencing of miR-27a-3p up-regulated the expression of RCBTB1（P＜0.01）. Bioinformatics analysis suggested that PFI and DSS in gastric cancer patients with low expression of RCBTB1 were decreased than those of patients with high expression of RCBTB1（P＜0.05）. In vitro experiments suggested that silencing RCBTB1 can enhance the aggressiveness of gastric cancer cells（P＜0.01）, while overexpression of RCBTB1 can inhibit it（P＜0.01, P＜0.05）. Compared with control group, the expression of E-cadherin was increased（P＜0.01）, the expression of Snail and β-catenin were decreased in Yiqi Huayu Jiedu Decoction containing serum group（P＜0.01, P＜0.05）. In vivo experiments showed that compared with the control group, the infiltration of gastric cancer cells in the liver tissues of Yiqi Huayu Jiedu Decoction group was reduced, the expression of miR-27a-3p, β-catenin and Snail in tumor tissues were down-regulated（P＜0.01）, and the expression of RCBTB1 and E-cadherin were up-regulated（P＜0.01, P＜0.05）. Conclusion: miR-27a-3p/RCBTB1/β-cateni is an important signal axis to promote EMT in gastric cancer. Yiqi Huayu Jiedu Decoction can regulate the signal of miR-27a-3p/RCBTB1/β-catenin to inhibit EMT, which plays an anti-metastasis role in gastric cancer.

王瑞平教授根据多年的临床经验将肺癌术后病理变化归结为正虚与邪实相争,正虚责于脾肺气虚,邪实则为术后残留之癌毒与用药稽留之药毒,二者常与血瘀、痰热、水湿等病理因素交结攻伐人体,而致正气虚,邪气盛.王教授认为一病多期是肺癌术后的基本病理状态,根据术后临床表现与癌毒动态变化可分为毒留期、毒郁期、毒恋期,并与肺癌术后瘀阻毒炽、痰热毒聚、正虚毒结证相合诊疗.治疗时权衡标本虚实之轻重,遵循"急攻缓补"的治疗原则,酌情施以化瘀、清热、补虚之法并将补脾益肺与抗癌解毒贯穿治疗始终,从而改善"血液高凝""炎-癌转化""免疫抑制"相关肿瘤微环境,提高术后患者生活质量,延长术后生存期.

Background The long non-coding RNA (lncRNA) RP9 pseudogene (RP9P) is a pseudogene-derived lncRNA that has never been reported in cancer, and its function underlying tumorigenesis in colorectal cancer (CRC) remains unknown. Methods RP9P and miR-133a-3p were filtered through bioinformatics analysis. The level of RP9P, miR-133a-3p, and FOXQ1 in CRC cell lines was detected by real-time PCR. Cell Counting Kit-8 and flow cytometric analyses were used to detect cell proliferation and apoptosis, respectively. Interactions between RP9P, miR-133a-3p, and FOXQ1 were confirmed by a dual-luciferase reporter assay. Results RP9P was overexpressed in CRC compared to normal control tissues and cells. Knockdown of RP9P inhibited CRC cell viability. RP9P directly interacted with miR-133a-3p, and miR-133a-3p downregulation abrogated the tumor-suppressing effect of RP9P knockdown. miR-133a-3p directly targeted FOXQ, which was positively regulated by RP9P. RP9P knockdown decreased FOXQ1 expression levels in CRC cells by directly targeting miR-133a-3p via a sponge mechanism. In addition, in vivo experiments in a xenograft model revealed that downregulated RP9P expression inhibited CRC cell tumorigenesis. Conclusion RP9P promotes colorectal cancer progression by regulating the miR-133a-3p/FOXQ1 axis.

目的:观察扶土疏木解毒汤对同时行化疗及靶向治疗的晚期大肠癌患者免疫功能及生存质量的影响.方法:将60例晚期大肠癌患者随机分为治疗组与对照组,每组30例.对照组予化疗+靶向治疗(贝伐珠单抗联合FOLFIRI),治疗组在对照组治疗的基础上加用中药汤剂扶土疏木解毒汤口服,均连续治疗8周后观察疗效.比较2组患者实体瘤疗效评价结果及治疗前后中医证候积分、行为状态评分(Karnofsky评分)、免疫功能(CD4+、CD8+、CD4+/CD8+)、生存质量评分变化情况.结果:治疗后治疗组实体瘤疗效评价总有效率(ORR)为60.00％、疾病控制率(DCR)为83.33％,对照组ORR为46.67％、DCR为80.00％,组间比较差异均无统计学意义(P>0.05).治疗后治疗组患者乏力、纳差等单项中医证候评分及总分均较治疗前明显降低(P<0.05),也明显低于对照组治疗后(P<0.05),而对照组上述评分治疗前后比较差异均无统计学意义(P>0.05).治疗组治疗后患者Karnofsky评分较治疗前明显升高(P<0.05),也明显高于对照组治疗后(P<0.05),而对照组治疗前后Karnofsky评分比较差异无统计学意义(P>0.05).治疗后,对照组患者CD4+、CD4+/CD8+均较治疗前明显降低(P<0.05),也明显低于治疗组(P<0.05),而治疗组CD4+、CD8+、CD4+/CD8+指标治疗前后比较差异均无统计学意义(P>0.05).治疗后,治疗组的生理状况、情感状况、功能状况、附加关注评分及生存质量总分均较治疗前显著升高(P<0.05),也明显高于对照组治疗后(P<0.05).结论:扶土疏木解毒汤辅助化疗、靶向治疗可显著改善晚期大肠癌患者临床症状,稳定免疫功能,提高患者的生存质量.

Colon adenocarcinoma (COAD) accounts for 95% of colon cancer cases, with the 5-year survival rate significantly affected by local or distant metastases. Yiqi Jianpi Huayu Jiedu decoction (YJHJD), based on the theory of “nourish qi, invigorate the spleen, remove blood stasis, and detoxify”, has long been applied and shown to be remarkable in the prevention and treatment of gastrointestinal tumors. However, the underlying therapeutic mechanisms of YJHJD have not been fully elucidated. Herein, we first confirmed hsa-miR-374a-3p as a tumor suppressor based on its lower expression in the plasma of patients with COAD with liver metastasis and association with more advanced local progression. We also verified WNT3 as a potential target of hsa-miR-374a-3p and observed its increased expression in COAD tissues. Furthermore, we showed that the hsa-miR-374a-3p/Wnt3/β-catenin axis was responsible for epithelial–mesenchymal transition (EMT) and cellular plasticity in COAD, as well as poorer patient prognosis. Our results showed that YJHJD inhibited motility and colony potential in vitro, as well as liver metastasis of COAD in vivo. Moreover, YJHJD induced a reversal of EMT and cellular plasticity-related molecular expression, increased hsa-miR-374a-3p, and decreased Wnt3 and β-catenin levels. In addition, silencing of hsa-miR-374a-3p weakened YJHJD inhibition, whereas the β-catenin inhibitor XAV939 partially repaired it. Taken together, these results demonstrated that YJHJD suppressed the EMT and cellular plasticity of COAD by regulating hsa-miR-374a-3p/Wnt3/β-catenin signaling.

目的 探讨益气健脾解毒方治疗中晚期胃癌疗效及对免疫功能和不良反应的影响.方法 选取2020年6月—2021年12月在江苏省中医院治疗的84例中晚期胃癌患者,随机分为对照组和观察组,每组42例.对照组给予XELOX方案化疗(卡培他滨+奥沙利铂,21 d为1个周期),观察组给予XELOX方案化疗+益气健脾解毒方口服,2组均治疗4个周期.观察2组治疗前后中医症状积分、血清免疫指标[白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)]和肿瘤标志物[糖类抗原125(CA125)、糖类抗原199(CA199)]水平变化,评估2组近期实体瘤疗效和不良反应发生情况.结果 治疗4个周期后,2组食少纳呆、恶心、腹胀、大便偏溏、上腹隐痛或刺痛积分及血清CA125、CA199水平均显著低于治疗前(P均<0.05),且观察组均显著低于对照组(P均<0.05);观察组血清IL-2、IFN-γ水平均显著高于治疗前及对照组(P均<0.05),IL-4、IL-6水平均显著低于治疗前及对照组(P均<0.05),而对照组IL-2、IFN-γ水平均显著降低(P均<0.05),IL-4、IL-6水平均显著升高(P均<0.05);观察组的客观缓解率与疾病控制率均显著高于对照组[64.3％(27/42)vs 42.8％(18/42)与88.1％(37/42)vs 66.7％(28/42)],差异均有统计学意义(P均<0.05).治疗期间,观察组胃肠道反应和肝肾损伤程度均明显轻于对照组(P均<0.05).结论 益气健脾解毒方可明显改善中晚期胃癌XELOX化疗患者的临床症状、免疫功能,抑制病情进展,并能明显减轻化疗不良反应.

Studies have revealed that β-asarone exerts a powerful inhibitory effect on the proliferation of human cancer cells. The authors' previous study demonstrated that β-asarone could induce LoVo colon cancer cell apoptosis in vitro and in vivo, indicating its anticancer properties. The present study aimed to determine the antineoplastic effect of β-asarone in HCT116 colon cancer cells. An in vitro proliferation assay using a real time cell analyzer demonstrated that β-asarone effectively decreased HCT116 cell proliferation in a dose-dependent manner. Bioinformatics analysis revealed that differentially expressed genes following β-asarone inhibition were involved in the 'cell cycle', 'cell division', 'cell proliferation' and 'apoptosis'. Subsequently, a xenograft assay evidenced the inhibitory effect of β-asarone on the growth of HCT116 tumors in vivo. Further detection of immune-associated cytokines and cells suggested that β-asarone might be involved in the antitumor immune response by stimulating granulocyte-colony stimulating factor and increasing the number of macrophage cells in the spleen. Additionally, a murine model of splenic-transplantation verified the strong suppressive role of β-asarone in colon cancer liver metastasis in vivo. Taken together, the results of the current study revealed that β-asarone decreased HCT116 colon cancer cell proliferation and liver metastasis potentially by activating the innate immune system, supporting the multi-system regulation theory and providing a basis for further mechanistic studies on colon cancer.

目的 观察胃癌患者血清肿瘤标志物的表达水平,并分析其与临床病理特征的相关性.方法 选取60例胃癌患者为试验组,60名健康者为对照组.比较两组的CA19-9、CA72-4、CA125和CEA水平;分析胃癌患者血清肿瘤标志物表达水平与临床病理特征的关系.结果 试验组的CA19-9、CA72-4、CA125和CEA水平均显著高于对照组,差异具有统计学意义(P<0.05).不同分化程度胃癌患者的血清CA125和CEA表达水平比较,差异具有统计学意义(P<0.05);不同浸润深度胃癌患者的血清CA19-9和CA72-4表达水平比较,差异具有统计学意义(P<0.05);淋巴结有、无转移胃癌患者的血清CA72-4、CA125和CEA表达水平比较,差异具有统计学意义(P<0.05);不同Her2表达情况胃癌患者的血清CA19-9、CA72-4和CEA表达水平比较,差异有统计学意义(P<0.05).结论 胃癌患者血清肿瘤标志物CA19-9、CA72-4、CA125和CEA均呈现高表达,对胃癌诊断具有重要提示作用;血清肿瘤标志物的阳性表达与临床病理特征之间存在密切联系,对胃癌病情进展评估及治疗方案的制定具有参考意义.

Abstract Background: Gastric cancer (GC) is one of the top 10 malignant tumors worldwide and poses a great threat to human life and health, the prevention and treatment of which has become the focus and difficulty of medical research. With its unique advantages, traditional Chinese medicine (TCM) is widely used in the prevention and treatment of postoperative recurrence and metastasis of GC as well as the improvement of patients’ quality of life. The aim of this study is to elucidate the curative effect and the underlying mechanism of Yiqi Huayu Jiedu (YQHYJD) decoction. Methods/design: This is a prospective, multicenter, randomized controlled trial continuing 3 years. Two hundred ninety-eight eligible patients will be randomly divided into 2 groups, the chemotherapy combined with placebo and the chemotherapy combined with YQHYJD group at a ratio of 1:1. All patients will receive the treatment for 6 months and follow up for 3 years. The primary outcomes are disease-free survival, and 1-year, 2-year, 3-year progression-free survival rate, while the secondary outcomes are tumor makers, TCM syndrome score, quality of life score, overall chemotherapy completion rate, intestinal flora diversity test, immune function (T, B lymphocyte subsets and NK cells) test. The Security index includes blood, urine and stool routine, electrocardiogram, liver function (ALT), and renal function (BUN, Scr). All of these outcomes will be analyzed at the end of the trial. Discussion: This research will provide the valuable evidence for the efficacy and safety of Yiqi Huayu Jiedu decoction in postoperative GC. Furthermore, it will be helpful to form a higher level of evidence-based medical basis for TCM in the treatment of GC recurrence and metastasis. Trial registration: ChiCTR2000039038

BackgroundThe modified Si-Jun-Zi Decoction (SJZ), a Chinese medicine formula, is clinically used against multiple malignancies including colorectal cancer (CRC). This study aims to evaluate the effect of modified SJZ on CRC liver metastasis and identify the therapeutic mechanisms.MethodsHuman CRC cells with GFP fluorescence were transplanted into Balb/c nude mice spleens. Modified SJZ, 5-fluorouracil or the combined treatment was given for 3weeks. CRC liver metastasis was measured by fluorescence imaging and plasma cytokines were analyzed. Furthermore, the effects of administration time and doses for the modified SJZ were investigated in nude mice.ResultsModified SJZ could increase the survival rate and reduce CRC liver metastasis in the nude mice model. Plasma GM-CSF level was elevated. Three weeks of treatment with the modified SJZ at the full dose (45g/kg) could significantly increase the number of macrophages but not neutrophils in the spleen.ConclusionsThese results indicate that modified SJZ can inhibit CRC liver metastasis by activating the innate immune system, providing a complementary and alternative therapy for CRC.

The Nm23 gene has been acknowledged to play a crucial role in lung cancer metastasis inhibitory cascades controlled by multiple factors. Low expression or allelic deletion of nm23-H1 is strongly linked to widespread metastasis and poor differentiation of non-small cell lung cancer (NSCLC). In this study, nm23-H1 was down regulated in epithelial-mesenchymal transition (EMT) and stemness enhancement under cobalt chloride (CoCl2)-induced hypoxia in NSCLC cells. Moreover, knocking down of nm23-H1 by shRNA apparently promoted hypoxia induced EMT and stemness, which was entirely suppressed via over expression of nm23-H1. Mechanistically, the Wnt/β-catenin signaling pathway was found to participate in the nm23-H1-mediated process. Besides, XAV939 prohibited cell EMT and stemness which could be impaired by knocking down of nm23-H1, while stable transfection of nm23-H1 attenuated hypoxia phonotype induced by lithium chloride (LiCl). Generally, our experiment provided evidence that nm23-H1 can reverse hypoxia induced EMT and stemness through the inhibition of the Wnt/β-catenin pathway, which may furnish a deeper perspective into the better treatment or prognosis for NSCLC.

Oxaliplatin has been widely applied in clinical tumor chemotherapy, the treatment failure of which mainly blames on low susceptibility resulted from intrinsic or acquired drug resistance in tumor cells. Microenvironmental hypoxia is one of the important pathological features of solid tumors, which is closely related to the radiochemotherapy tolerance and poor prognosis. Cinnamaldehyde is extracted from Cinnamomum cassia with inhibiting effect against kinds of tumors. In this study, we demonstrated that hypoxia reduced the sensitivity to oxaliplatin in colorectal cancer (CRC) cells via inducing EMT and stemness. Nonetheless, cinnamaldehyde increased the curative effect of oxaliplatin by promoting apoptosis both in vitro and in vivo. Mechanistically, cinnamaldehyde and oxaliplatin synergistically reversed hypoxia-induced EMT and stemness of CRC cells and suppressed hypoxia-activated Wnt/β-catenin pathway synergistically. These consequences uncovered the potential therapeutic value of cinnamaldehyde and provided novel ideas on improving the sensitivity of oxaliplatin in CRC therapy.

从中医阴阳理论探讨自噬与肿瘤之间的相互关系.自噬与肿瘤的发病密切相关,既有抑制作用,亦有促进作用,自噬的降解和代谢途径与中医阴阳理论的相互制约、相互为用、相互转化有着相似的内涵.运用中医阴阳理论,促进或抑制自噬,调和阴阳平衡,为更好地治疗肿瘤提供可能.