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1.
Drug Des Devel Ther ; 18: 881-897, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529263

RESUMO

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Vesícula Biliar , Gastrite Atrófica/tratamento farmacológico , Glicerofosfolipídeos , Temperatura Alta , Baço , Estudos Controlados Antes e Depois , Estudos de Casos e Controles
2.
J Ethnopharmacol ; 319(Pt 2): 117211, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37739100

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea L. (PO), popularly known as purslane, has been documented in ethnopharmacology in various countries and regions. Traditional application records indicated that PO might be used extensively to treat the common cold, dysentery, urinary tract infections, coughing, eye infections, skin problems, gynecological diseases, and pediatric illnesses. AIM OF THE REVIEW: This paper includes a systematic review of the traditional usage, phytochemicals, pharmacological activity, and potential uses of PO to provide an overview of the research for further exploitation of PO resources. MATERIALS AND METHODS: This article uses "Portulaca oleracea L." and "purslane" as the keywords and collects relevant information on PO from different databases, including PubMed, Web of Science, Springer, Science Direct, ACS, Wiley, CNKI, Baidu Scholar, Google Scholar, and ancient meteria medica. RESULTS: PO is a member of the Portulacaceae family and is grown worldwide. Traditional Chinese medicine believes that purslane has the effect of improving eyesight, eliminating evil qi, quenching thirst, purgation, diuresis, hemostasis, regulating qi, promoting hair growth, detoxifying, and avoiding epidemic qi. Recent phytochemical investigations have shown that PO is a rich source of flavonoids, homoisoflavonoids, alkaloids, organic acids, esters, lignans, terpenoids, catecholamines, sterols, and cerebrosides. The purslane extracts or compounds have exhibited numerous biological activities such as anti-inflammatory, immunomodulatory, antimicrobial, antiviral, antioxidant, anticancer, renoprotective, hepatoprotective, gastroprotective, metabolic, muscle relaxant, anti-asthmatic and anti-osteoporosis properties. The significant omega-3 fatty acids, vital amino acids, minerals, and vitamins found in purslane also provide nutritional benefits. Purslane as a food/feed additive in the food industry and animal husbandry has caused concern. Its global wide distribution and tolerance to abiotic stress characteristics make it in the future sustainable development of agriculture a certain position. CONCLUSIONS: Based on traditional usage, phytochemicals, and pharmacological activity, PO is a potential medicinal and edible plant with diverse pharmacological effects. Due to purslane's various advantages, it may have vast application potential in the food and pharmaceutical industries and animal husbandry.


Assuntos
Portulaca , Animais , Criança , Humanos , Etnofarmacologia , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Portulaca/química
3.
Am J Chin Med ; 51(8): 1957-1981, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37884447

RESUMO

The gut microbiome (GM) has become a crucial factor that can affect the progression of osteoporosis. A number of studies have demonstrated the impact of Traditional Chinese Medicine (TCM) on GM and bone metabolism. In this review, we summarize the potential mechanisms of the relationship between osteoporosis and GM disorder and introduce several natural Chinese medicines that exert anti-osteoporosis effects by modulating the GM. It is underlined that, through the provision of the microbial associated molecular pattern (MAMP), the GM causes inflammatory reactions and alterations in the Treg-Th17 balance and ultimately leads to changes in bone mass. Serotonin and many hormones, especially estrogen, may play a crucial role in the interaction of the GM with bone metabolism. Additionally, the GM may affect the absorption of specific nutrients in the intestine, particularly minerals like calcium, magnesium, and phosphorus. Several natural Chinese herbs, such as Sambucus Williamsii, Achyranthes bidentata Blume, Pleurotus ostreatus and Ganoderma lucidum mushrooms, Pueraria Lobata, and Agaricus blazei Murill have exhibited anti-osteoporosis effects through regulating the distribution and metabolism of the GM. These herbs may increase the abundance of Firmicutes, decrease the abundance of Bacteroides, promote the GM to produce more SCFAs, modulate the immune response caused by harmful bacteria, and increase the proportion of Treg-Th17 to indirectly affect bone metabolism. Moreover, gut-derived 5-HT is an important target for TCM to prevent osteoporosis via the gut-bone axis. Puerarin could prevent osteoporosis by improving intestinal mucosal integrity and decrease systemic inflammation caused by estrogen deficiency.


Assuntos
Microbioma Gastrointestinal , Osteoporose , Humanos , Medicina Tradicional Chinesa , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Densidade Óssea , Inflamação , Estrogênios
4.
Neoplasma ; 70(3): 443-450, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37498067

RESUMO

The 5-year survival rate for patients with lung cancer, the world's second most frequent malignant tumor, is less than 20%, and its prognosis cannot be clearly predicted. Our aim was to analyze the epidermal growth factor receptor (EGFR) rs763317 (G>A) single nucleotide polymorphism and its association with prognosis in Chinese Han lung cancer patients. 839 patients with primary lung cancer were recruited, and genomic DNA was extracted and genotyped by SNPscan. Kaplan-Meier technique and multivariate Cox proportional hazards model were used to analyze the association between prognosis and EGFR polymorphism rs763317. A significant association after stratification by age, significantly increased lung cancer risk was associated with the AA homozygous genotype of rs763317 (adjusted hazard ratio = 2.53, 95% CI: 1.31-4.88, p=0.005), and conferred a poor survival for lung cancer patients (MST: median survival time: 13.6 months) compared with GG genotype (MST: 41.5 months), and in the recessive model AA genotype (AA vs. GG + GA; adjusted hazard ratio = 2.57, 95% CI: 1.34-4.93, p=0.004) who were young (<60 years) had a significantly increased risk of death. The EGFR polymorphism rs763617 might serve as a significant genetic marker for predicting the prognosis of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , População do Leste Asiático , Receptores ErbB/genética , Predisposição Genética para Doença , Genótipo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico
5.
Oncol Rep ; 49(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36866751

RESUMO

Gastric cancer (GC) develops in a complex tissue environment, the tumor microenvironment (TME), which it relies on for persistent proliferation, migration, invasion and metastasis. Non­malignant 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 factor­ß from tumor cells, immune cells, cancer­associated 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 cell­directed agents or emerging immunotherapies becoming a desirable modality in the management of GC and acquire improved outcomes for patients with GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Qualidade de Vida , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular
6.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 172-176, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38279448

RESUMO

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Apoptose , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
7.
Chin Med ; 17(1): 139, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517857

RESUMO

BACKGROUND: Chaihu-Guizhi-Ganjiang Decoction (CGGD) is a traditional Chinese medicine (TCM) prescription used to treat viral influenza. There is evidence that CGGD can be used to treat irritable bowel syndrome (IBS) but the potential mechanism of action and metabolites produced upon CGGD treatment remains elusive. METHODS: Patients with IBS were treated with pinaverium bromide (Dicetel™) and then CGGD after a washout period of 1 week. Both treatments lasted for 30 days. The efficacy and changes of metabolites in plasma after the two treatments were compared. Plasma samples were acquired before and after each treatment, and untargeted metabolics analysis was performed. RESULTS: Efficacy was measured according to the Rome IV criteria and TCM theory. Our results indicated that CGGD showed significantly better efficacy than Dicetel in the treatment of IBS utilizing each criterion. CGGD exerted greater effects on plasma metabolism than Dicetel. Dicetel treatment led to increased tryptophan metabolism (increased levels of 5-Hydroxyindoleacetaldehyde) and increased protein metabolism (increased levels of L-arginine). CGGD treatment significantly (p < 0.05) increased carnitine metabolism, with elevated levels of L-carnitine and acylcarnitine in plasma. Such changes in these metabolites could exert effects against IBS by improving gastrointestinal motility and suppressing pain, depression, and inflammation. CONCLUSIONS: CGGD appeared to be more efficacious than Dicetel for treating patients with IBS. The findings provide a sound support for the underlying biomolecular mechanism of CGGD in the prevention and treatment of IBS.

8.
Int J Med Sci ; 19(13): 1835-1846, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438913

RESUMO

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.


Assuntos
RNA Longo não Codificante , Receptor PAR-1 , Neoplasias Gástricas , Humanos , Apoptose/genética , Proliferação de Células/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor PAR-1/genética , Receptor PAR-1/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
9.
Int J Clin Pharmacol Ther ; 60(12): 509-514, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36197788

RESUMO

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.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Trastuzumab/uso terapêutico , Paclitaxel , Terapia de Alvo Molecular
10.
Dis Markers ; 2022: 1360954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051356

RESUMO

Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.


Assuntos
Antineoplásicos , Neoplasias Colorretais , MicroRNAs , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico
11.
Environ Toxicol ; 37(12): 2957-2964, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36039874

RESUMO

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.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias , Proteína Jagged-1/metabolismo , Proteínas Serrate-Jagged/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células , Proteínas de Membrana/metabolismo , Transdução de Sinais
13.
J Integr Med ; 20(4): 355-364, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35249836

RESUMO

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.


Assuntos
Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , China , Regulação Neoplásica da Expressão Gênica , Camundongos , Camundongos Nus , Invasividade Neoplásica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
14.
Front Oncol ; 11: 618793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747930

RESUMO

BACKGROUND: Chemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting. METHODS: In this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity. RESULTS: A total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms. CONCLUSIONS: Chemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32849898

RESUMO

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.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32774431

RESUMO

The red peony root derived from Paeonia lactiflora has been applied to treat human inflammatory diseases. To investigate its therapeutic potential in treating moderately severe acute pancreatitis (MSAP), which has been rarely studied, this study was designed as a double-blinded, placebo-controlled, randomized clinical trial. A total of 60 MSAP patients were enrolled and randomly divided into an experimental (n = 30) group and a control group (n = 30), who received a coloclyster of 15 g of red peony root or placebo granules dissolved in 150 mL of water, respectively. The patients' demographic and clinical characteristics were recorded. The results showed that the experimental group had a shorter remission time of fever (p < 0.05) and abdominal pain (p < 0.01) and faster resumption of self-defecation (p < 0.01) than did the control group. In addition, the coloclyster of red peony root decreased the modified Balthazar CT score as well as the serum interleukin-6 and tumor necrosis factor-alpha levels to a greater extent than did the placebo coloclyster (p < 0.05). The remission times for the normalization of white blood cells and percentage of neutrophils and lymphocytes in the experimental group were also significantly shorter than those in the control group (p < 0.05). In conclusion, a coloclyster of red peony root could help alleviate the clinical symptoms and shorten the course of MSAP by possibly attenuating systematic inflammation. This trial is registered with 14004664.

17.
Int J Clin Exp Pathol ; 13(5): 846-853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509055

RESUMO

OBJECTIVE: To investigate the anti-gastric precancerous lesions effect and mechanism of Traditional Chinese Medicine Jinlongshe (JLS) granules in ethanol extractive of A. manshuriensis (EEA)-induced gastric precancerous lesions rats. METHODS: A rat model with the part typical proliferation of the gastric epithelium mucosa was established by EEA. These rats received different doses of JLS granules treatment for four weeks. Bodyweight, histological and ultrastructural changes of gastric precancerous lesions were evaluated. The expression of Apelin and CD34 mRNA and proteins of the gastric tissue were analyzed by quantitative Realtime PCR, western blot and immunohistochemical staining. RESULTS: We found that the treatment of JLS granules prevented the bodyweight loss and improved behavioral abnormalities of rats that received EEA. The histological and ultrastructural analysis also showed that JLS granules ameliorated EEA induced gastric precancerous lesions in a dose-dependent manner. The expression levels of two critical proteins involved in the angiogenesis of gastric carcinoma, Apelin, and CD34, were significantly reduced by the treatment of JLS granules. CONCLUSION: Our results indicated that JLS could inhibit the expression of the Apelin and CD34 genes in rat gastric mucosa, which reversed gastric precancerous lesions.

18.
Biomed Res Int ; 2020: 2018162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32382534

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Biol Pharm Bull ; 43(2): 348-355, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776306

RESUMO

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-κB) 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 28 d 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-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) 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-κB and mitigating neuroinflammation.


Assuntos
Curcumina/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/metabolismo , Neuralgia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Hiperalgesia/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Condução Nervosa/efeitos dos fármacos , Neuralgia/induzido quimicamente , Oxaliplatina , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Biomed Pharmacother ; 108: 95-102, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30218863

RESUMO

In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas/uso terapêutico , NF-kappa B/metabolismo , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Hiperplasia , Metilnitronitrosoguanidina , Ratos Wistar , Acetato de Tetradecanoilforbol/farmacologia
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