Introduction: Traditional Chinese medicine has been shown to improve survival and immune function in patients with advanced gastric cancer (AGC). Objectives: This study aimed to evaluate the efficacy of a phlegm-resolving regimen (Ziyin Huatan recipe combined with Xiaoaiping injection) and syndrome differentiation-guided therapy combined with various antineoplastic Chinese patent medicine injections in AGC. Methods: Data from 150 patients with AGC were retrospectively analyzed: 75 in the study group and 75 in the control group. The clinical data were analyzed, including Karnofsky Performance Status (KPS), 1-, 2-, and 3-year survival rates, overall survival (OS), median OS, progression-free survival (PFS), and median PFS. Results: At 3 months, the mean KPS score significantly increased from 55.33 ± 6.44 to 73.07 ± 8.70 in the study group (p = 0.001 [< 0.01]), and from 54.93 ± 6.23 to 72.40 ± 8.67 (p = 0.001 [< 0.01]) in the control group. There was no significant difference in the changes of KPS score between the two groups. The median OS was 17.0 months in the study group (95% confidence interval [CI]: 13.16–20.84) versus 14.7 months in the control group (95% CI: 8.89–20.51). There was no significant difference in the OS between the two groups. The median PFS was 16.0 months in the study group (95% CI: 11.17–16.83) versus 12.0 months in the control group (95% CI: 7.48–16.52). The 1-year and 3-year PFS rates in the study group were higher than in the control group (61.33% versus 49.3% and 21.3% versus 14.7%, respectively). Conclusion: Our retrospective study suggests that phlegm-resolving regimens may confer survival benefits in patients with AGC; accordingly, such regimens can be considered for incorporation into standardized treatment strategies.
Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non‑malignant stromal cell types within the TME are regarded as a clinical meaningful target with the lower risk of resistance and tumor relapse. Studies have revealed that the Xiaotan Sanjie decoction, which is formulated on the basis of the theory of phlegm syndrome, a Traditional Chinese Medicine concept, modulates released factors such as transforming growth factor‑β from tumor cells, immune cells, cancer‑associated fibroblasts, extracellular matrix, as well as vascular endothelial growth factor involved in the process of angiogenesis within the TME. Clinical studies have also shown that the Xiaotan Sanjie decoction is associated with favorable survival and quality of life. The present review aimed to interpret the hypothesis that Xiaotan Sanjie decoction has the ability to normalize the GC tumor cells by influencing functions of stromal cells within the TME. The possible association between phlegm syndrome and the TME in GC was discussed in the present review. Overall, Xiaotan Sanjie decoction may be suitable to be added to tumor cell‑directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.
Abstract Colitis‐associated bowel cancer (CAC) is one of the most common malignancies associated with inflammation. The aim of this study was to observe a new herbal formula “Xiaotan Sanjie Fang” (XTSJF) derived from the addition and subtraction theory of traditional medicine as an alternative to CAC treatment by “Daotan Decoction” and “Xiaojianzhong Decoction”, which are famous traditional Chinese medicine prescriptions for the treatment of inflammatory diseases of the digestive tract. We constructed a DMH/DSS inflammation‐associated colorectal cancer rat model and treated CAC rats with sulfasalazine and different doses of XTSJF. The results showed that the body weight of rats treated with different doses of XTSJF increased, which was still lower than that of normal rats; AFC decreased significantly compared with the model group and the positive control group, and the final dose was superior to the low dose; histological observation revealed that it could maintain the normal structure of colon tissue, while it could inhibit the secretion of VEGF, COX2, and AQP1 and the expression of pro‐inflammatory cytokines IL‐6, IL‐1β, and TNF‐α, promote the expression of caspase‐3 and BAX and inhibit the expression of Bcl‐2. Taken together, these data suggest that XTSJF can inhibit COX‐2/VEGF expression to prevent the development of inflammation‐associated colorectal cancer.
OBJECTIVES:Ziyin Huatan Recipe (ZYHT), a traditional Chinese medicine comprised of Lilii Bulbus, Pinelliae Rhizoma, and Hedyotis Diffusa, has shown promise in treating gastric cancer (GC). However, its potential mechanism has not yet been clearly addressed. This study aimed to predict targets and molecular mechanisms of ZYHT in treating GC by network pharmacology analysis and to explore the role of ZYHT in GC both in vitro and in vivo.METHODS:Targets and molecular mechanisms of ZYHT were predicted via network pharmacology analysis. The effects of ZYHT on the expression of metastasis-associated targets were further validated by Western blot and quantitative real-time polymerase chain reaction. To explore the specific molecular mechanisms of the effects of ZYHT on migration and invasion, the runt-related transcription factor 3 (RUNX3) gene was knocked out by clustered regularly interspaced short palindromic repeats/Cas9, and lentiviral vectors were transfected into SGC-7901 cells. Then lung metastasis model of GC in nude mice was established to explore the anti-metastasis effect of ZYHT. Western blot and immunohistochemistry were used to explore the impact of ZYHT on the expression of metastasis-related proteins with or without RUNX3 gene.RESULTS:The network pharmacology analysis showed that ZYHT might inhibit focal adhesion, migration, invasion and metastasis of GC. ZYHT inhibited the proliferation, migration and invasion of GC cells in vitro via regulating the expression of metastasis-associated targets. Knocking out RUNX3 almost completely reversed the cell phenotypes (migration and invasion) and protein expression levels elicited by ZYHT. In vivo studies showed that ZYHT inhibited the metastasis of GC cells to the lung and prolonged the survival time of the nude mice. Knocking out RUNX3 partly reversed the metastasis of GC cells to the lung and the protein expression levels elicited by ZYHT.CONCLUSION:ZYHT can effectively inhibit the invasion and migration of GC in vitro and in vivo, and its molecular mechanism may relate to the upregulation of RUNX3 expression.
Objective: To determine the effect and mechanism of the long non-coding RNA (lncRNA) ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]) in human gastric cancer. Methods: HGC-27-ncRuPAR overexpression and MGC-803-ncRuPAR-RNAi knockdown gastric cancer cell lines were established. We assessed the effect of ncRuPAR on cell proliferation, apoptosis, migration, and invasion using Cell Counting Kit 8, flow cytometry, scratch and transwell assays, respectively. Differentially expressed genes in HGC-27-ncRuPAR overexpression and HGC-27-empty vector cell lines were identified using Affymetrix GeneChip microarray analysis. Ingenuity Pathway Analysis (IPA) of the microarray results was subsequently conducted to identify ncRuPAR-enriched pathways, followed by validation using real time-quantitative PCR (RT-qPCR). As one of the top enriched pathways, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was further examined by western blotting to determine its role in ncRuPAR-mediated regulation of gastric cancer pathogenesis. Results: ncRuPAR inhibited human gastric cancer cell proliferation and induced G1/S phase arrest and apoptosis, but did not affect migration or invasion in vitro. Overexpression of ncRuPAR in vitro was found to inhibit its known target PAR-1, as well as PI3K/Akt signaling. The downstream targets of PI3K/Akt, cyclin D1 was downregulated, but there was no change in expression level of B-cell lymphoma 2 (Bcl-2). Conclusions: We showed that lncRNA-ncRuPAR could inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells, potentially by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1. The results suggest a potential role for lncRNAs as key regulatory hubs in GC progression.
Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.
The purpose of this study is to explore the anti-colorectal cancer of Xiaotansanjiefang, a famous traditional Chinese medicine, and its potential anti-cancer mechanism. In this study, the HCT116 cell spheres were prepared as in vitro study model. We found the Xiaotansanjiefang medication was able to inhibit the proliferation of HCT116 cell spheres in a dose-dependent manner, especially in 3 and 6 mg/ml Xiaotansanjiefang medication treated groups. We also found the high concentration of Xiaotansanjiefang medication could suppress the migration and promote the apoptosis of HCT116 cell spheres. Moreover, we found the expression of Jagged 1, Notch 3, Snail, and Hes 1 were decreased in HCT116 cell spheres treated with Xiaotansanjiefang medication. Furthermore, the proliferation and apoptosis behaviors of HCT116 cell spheres treated with Xiaotansanjiefang medication were reversed with the addition of Jagged 1 Fc chimera protein. The expression of Jagged 1, Notch 3, Snail, and Hes 1 were also increased again in HCT116 cells treated with Xiaotansanjiefang medication plus with Jagged 1 Fc chimera protein. The presented study may provide a promising strategy to treat and prevent colorectal cancer.
目的 观察中药白龙解郁颗粒对执行出海任务的海军官兵心理应激的预防作用.方法 以执行出海任务的海军官兵209人作为研究对象,按随机数表法将其分为白龙解郁颗粒组(n=103)和空白组(n=106).于出海第1周时采用心理应激自评问卷(PSET)及90项症状自评量表(SCL-90)对两组官兵进行问卷调查.白龙解郁颗粒组官兵在出海第3周时给予白龙解郁颗粒干预,空白组不给予干预措施.出海第4周时两组分别复测PSET及SCL-90,并进行组间对照分析.结果 两组的基线资料基本一致,白龙解郁颗粒组与空白组在出海第1周时的PSET、SCL-90各因子分差异均无统计学意义(P均>0.05).空白组出海第4周时的PSET标准分高于出海第1周(P<0.05).白龙解郁颗粒组出海第1周和第4周的PSET标准分比较差异无统计学意义(P>0.05).出海第4周时白龙解郁颗粒组的PSET标准分低于空白组,差异有统计学意义(P<0.05).出海第4周时空白组SCL-90的躯体化、强迫症状、人际关系敏感、抑郁、焦虑、敌对、恐怖、偏执、精神病性及其他因子分均高于出海第1周时,差异均有统计学意义(P均<0.05).出海第4周时白龙解郁颗粒组SCL-90的抑郁、恐怖、偏执、精神病性因子分均低于空白组出海第4周时,差异均有统计学意义(P均<0.05).结论 白龙解郁颗粒对执行出海任务的海军官兵具有预防军事应激反应的作用.
Background and Objective Neurotoxicity is a common side effect of oxaliplatin; the effect of current drugs such as methylcobalamin and gabapentine is not obvious. Astragaloside IV (AS-IV) is an important active ingredient of Astragali Radix, which can protect the nervous system and inhibit tumor growth to a certain extent. However, whether AS-IV can reduce oxaliplatin neurotoxicity and its molecular mechanism remain unclear. Methods The network pharmacology method was used to determine the collective targets of AS-IV and oxaliplatin neurotoxicity. The model of neurotoxicity was established by intraperitoneal injection of oxaliplatin in rats. Bodyweight, mechanical withdrawal threshold (MWT), cold allodynia, and nerve conduction velocity (NCV) were examined, pathological changes were observed by hematoxylin-eosin staining, number of Nissl bodies were assessed by Nissl staining, the key collective targets were measured by spectrophotometry and immunohistochemistry. Results Through network pharmacological analysis, 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified, mainly related to inflammation and oxidative stress. AS-IV could increase body weight, elevate MWT, and reduce cold allodynia of model rats, it also raised NCV. Neuropathology was improved and the number of Nissl bodies was increased by AS-IV administration. It reduced TNF-α, IL-6, and IL-1β in the spinal cord of model rats to inhibit inflammation; it also decreased MDA, raised SOD, CAT, and GSH-Px in the spinal cord of model rats to block oxidative stress. Conclusion AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.
文章针对目前西医院校中医学课程普遍存在的教学效果不佳现状进行分析,将问题归纳为教学针对性差、授课方式陈旧、考核方式单一、教学思路不清晰等几个方面,通过总结教学经验,提出了"明确教学目标,编写创新教材""围绕学以致用,改革教学模式""借助信息技术,辅以MOOC教学""针对技能教学,创新考试方式"等一系列教改措施.实践证实,学生的学习兴趣大大提高,中医药动手能力明显增强,考试成绩优秀率稳步提升.这一措施可为医学院校的中医学课程教学改革提供一定参考.
This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.
"癌毒"是近年来中西医结合肿瘤防治领域的重要创新性概念,是导致恶性肿瘤发生的根本原因,更是影响其转归、预后的关键因素之一.本文着眼于"癌毒"这一核心病机,围绕癌毒辨识及其临床特点,从断其根、易其性和化其形三方面,提出了围绕"癌毒"治疗诸多相应治法及用药思路,希望为深化中医药对癌毒的认识以及提高中西医结合诊治恶性肿瘤的水平提供一定借鉴与参考.
Background/Aims . In previous studies, it has been observed that Xiaotan Jieyu (XTJY) prescription may inhibit the proliferation of human breast precancerous lesion MCF‐10AT cells by inhibiting the PI3K/Akt signaling pathway. The purpose of this study is to further verify the therapeutic effect and the possible mechanism of XTJY on precancerous lesions of breast cancer in vivo. Methods . The successfully established breast precancerous lesion rat model and normal healthy rats were randomly assigned into the blank (BLA), model (MOD), XTJY‐low (LD), XTJY‐medium (MD), XTJY‐high (HD), and tamoxifen (TAM) groups. Different concentrations of XTJY and saline were supplied by intragastric administration for 4 consecutive weeks to assess the protective effect of XTJY on the progress of the breast precancerous lesion in rats involving the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway. Results . In this study, it determined that 10 mg/each rat DMBA‐combined estrogen and progesterone induction for 10 weeks was the optimal condition for the establishment of the breast precancerous lesion rat model. In vivo administration of XTJY or TAM was found to inhibit the development of the breast precancerous lesion, and the occurrence rate of breast invasive carcinomas was decreased by about 50%. Furthermore, XTJY or TAM markedly reduced protein expressions of PI3K and p‐Akt and increased protein expressions of PTEN. Conclusion . These data indicated that XTJY can significantly alleviate the development of breast precancerous lesions by inhibiting the activation of the PI3K/Akt signaling pathway. XTJY may be a promising drug for the treatment of precancerous lesions in breast cancer.
In recent years, traditional Chinese medicine has played an important role in the treatment of gastric cancer in China. ZiYinHuaTan (ZYHT) recipe was developed for advanced gastric cancer and had shown its promising value in the clinic. In this study, we explore the effect of ZYHT on gastric cancer in vitro and in vivo. ZYHT can inhibit tumor growth and improve the general condition of mice in subcutaneous transplantation nude mice models of gastric cancer. And ZYHT can also inhibit cell proliferation and blocked the cells in G0/G1 to induce cell apoptosis in HGC27 and MGC803 cells. Then, network pharmacology analysis showed that ZYHT may exert antitumor effect mainly through PI3K/AKT signaling pathway. Furthermore, the expression of PI3K, p-Akt, CyclinD1, and Bcl-2 was detected in vitro and in vivo. The results showed that ZYHT could decrease the expression of PI3K, CyclinD1, and Bcl-2 both in vitro and in vivo. These results suggested that ZYHT could be used as a method for the treatment of developed gastric cancer.
Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-kappa B) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-kappa B and level of inflammatory factors like tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-kappa B and mitigating neuroinflammation.
目的 观察消痰散结中医治疗方案(金龙蛇口服液+鸦胆子油乳注射液)用于肠癌术后患者的临床疗效和毒性反应,以及其对患者免疫功能和生活质量的影响.方法 选择68例结直肠癌术后患者并根据患者意愿分为消痰散结组(36例)和化学治疗组(32例),前者采用消痰散结中医治疗方案(金龙蛇口服液+鸦胆子油乳注射液),后者采用卡培他滨联合奥沙利铂(XELOX)方案,治疗6个周期.观察2组患者肿瘤标志物、中医临床症候积分、毒性反应、免疫功能和生活质量(卡氏评分)的变化.结果 治疗6个周期后,消痰散结组癌胚抗原(CEA)、糖类抗原19-9(CA19-9)与化学治疗组相比差异均无统计学意义(P均>0.05),两组中医临床症候积分差异无统计学意义(P>0.05).消痰散结组出现白细胞减少、手足综合征、过敏等毒性反应的患者比例均低于化学治疗组(P均<0.05).两组患者治疗后CD4+、CD8+T淋巴细胞亚群比例与治疗前相比均下降,差异均有统计学意义(P均<0.05);两组间CD3+、CD4+、CD8+T淋巴细胞亚群比例及CD4+/CD8+T淋巴细胞比值差异无统计学意义(P>0.05).消痰散结组卡氏评分高于化学治疗组,差异有统计学意义(P<0.05).结论 与XELOX化学治疗方案相比,消痰散结中医治疗方案用于结直肠癌术后患者可减轻毒性反应,提高患者生活质量.
Objective: To evaluate the therapeutic efficacy and explore the action mechanism of Xiaotan Sanjie Formula (XSF) on microsatellite instability (MSI) in human gastric cancer MKN-45 cells. Methods: The therapeutic efficacy of XSF on human gastric cancer MKN-45 cell proliferation was detected by CCK-8. Five MSI loci (D17S250, D2S123, D5S346, Bat-25 and Bat-26) were detected by STR Genotyping. The effect of XSF on the expression of MSI proteins of hMLH1, TGF beta RII, IGFRII and Bax was analyzed by Western blot and RT-PCR. Results: XSF inhibited the proliferation of human gastric cancer MKN-45 cells in a time-dependent manner. When these MKN-45 cells were amplified to the five MSI loci, both D2S123 and D5S346 showed MSI with two peaks. After 48-h intervention with XSF, the mutation of D2S123 and D5S346 loci tended to be stabilized; the relative expression level of hMLH1, TGF beta RII and Bax mRNA was increased in varying degrees, and the expression level of IGFRII mRNA tended to decrease, while the expression level of IGFRII protein was increased significantly (P<0.05). Conclusion: XSF inhibited MSI of human gastric cancer MKN-45 cells, probably by up-regulating MSI-associated hMLH1, TGF beta RII, IGFRII and Bax gene and protein expressions, and IGFRII protein expression.
癌痛是恶性肿瘤最常见、最痛苦的症状之一,受到全球医学界的广泛关注.尽管目前"三阶梯止痛方案"在一定程度上可减轻癌痛,但政策法规、社会人文因素等使癌痛的控制仍不理想.中医外治通过施药于外而作用于内,与化学药止痛相比具有疗效可靠、使用安全、无成瘾性及戒断性等优点.在中医痰证理论指导下,结合癌痛临床症状,本文提出"消痰止痛"为其主要治法,治疗效果满意.