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1.
Front Oncol ; 14: 1361562, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903713

RESUMEN

Purpose: The purpose of this study was to describe an approach to cervical brachytherapy for a patient with a complete bicorporeal uterus and locally advanced cervical cancer (LACC). Materials and methods: The patient was a 53-year-old woman with a complete bicorporeal uterus, diagnosed with stage IIB cervical squamous cell carcinoma due to contact bleeding. The patient underwent concurrent chemoradiotherapy (CCRT), external beam pelvic radiotherapy with 45 Gy/25 fractions, and weekly cisplatin (40 mg/m2). Brachytherapy was administered following the completion of external beam radiotherapy. Results: The brachytherapy, which was CT (Computed Tomography)-guided using two CT-compatible tandems and two CT-compatible ovoids, delivered a prescription dose of HRCTV D90 was 6 Gy*5F, which achieved satisfactory dose coverage. The patient's final HRCTV D90 EQD210 was 84.9 Gy, and IRCTV D90 EQD210 was 63.5 Gy. Rectum D2cc EQD23 was 66.03 Gy, bladder D2cc EQD23 was 75.57 Gy, sigmoid D2cc EQD23 was 63.93 Gy, and intestine D2cc EQD23 was 65.86 Gy. Follow-up at 1 year was CR. Conclusions: For patients with cervical cancer and a complete bicorporeal uterus, using double tandems combined with double ovoids is a feasible treatment method to ensure adequate dose coverage without causing additional damage. This method is also applicable to patients with endometrial cancer.

2.
Sci Rep ; 14(1): 8604, 2024 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-38615057

RESUMEN

This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of < 32.91 cm2/m2, initial tumor size ≥ 3.335 cm, and a glucose-to-neutrophil ratio (GLR) ≥ 2.88 were identified as independent risk factors for severe hematologic toxicity during neoadjuvant chemotherapy in luminal-type breast cancer patients. The sample size in this study is small, and the predictive capacity of GLR in hematologic toxicity requires further research for comprehensive validation. CT-L1 analysis represents a viable alternative to CT-L3 analysis for body composition assessment. Patients with a low skeletal muscle index were more prone to experiencing severe hematologic toxicity during neoadjuvant chemotherapy.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante/efectos adversos , Estudios Retrospectivos , Músculo Esquelético/diagnóstico por imagen , Tomografía Computarizada por Rayos X
3.
Biochim Biophys Acta Rev Cancer ; 1878(3): 188884, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36990250

RESUMEN

The vagus nerve (VN) is the main parasympathetic nerve of the autonomic nervous system. It is widely distributed in the gastrointestinal tract and maintains gastrointestinal homeostasis with the sympathetic nerve under physiological conditions. The VN communicates with various components of the tumor microenvironment to positively and dynamically affect the progression of gastrointestinal tumors (GITs). The intervention in vagus innervation delays GIT progression. Developments in adeno-associated virus vectors, nanotechnology, and in vivo neurobiological techniques have enabled the creation of precisely regulated "tumor neurotherapies". The present review aimed to summarize the mechanisms of communication between the VN and the gastrointestinal TME and to explore the potential and challenges of VN-based tumor neurotherapy in GITs.


Asunto(s)
Neoplasias Gastrointestinales , Fenómenos Fisiológicos del Sistema Nervioso , Humanos , Nervio Vago/fisiología , Homeostasis , Microambiente Tumoral
4.
Front Oncol ; 12: 899335, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35847887

RESUMEN

Purpose: This research investigated the predictive role of metabolic syndrome (MetS) in breast cancer neoadjuvant chemotherapy (BCNACT) response. Methods: One hundred fifty primary breast cancer (BC) patients who underwent neoadjuvant chemotherapy (NACT) were included retrospectively. MetS, MetS components [waist circumference (WC), fasting blood glucose (FBG), blood pressure, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)], serum lipid, and other MetS-related laboratory indicators within two weeks before BCNACT were evaluated. Univariate, multivariate, and subgroup analyses were performed to determine the predictors of BCNACT pathologic complete response (pCR), clinical response, and pathologic response. The effectiveness of the model was evaluated via receiver operating characteristic curve (ROC) and calibration curve. External validation was performed through 135 patients. Results: Univariate analysis revealed that MetS before BCNACT predicted poor BCNACT response (pCR, P = 0.003; clinical response, P = 0.033; pathologic response, P < 0.001). Multivariate analysis confirmed that MetS before BCNACT predicted lower pCR rate (P = 0.041). Subgroup analysis showed that this relationship was significant in estrogen receptor (ER) (-) (RR = 0.266; 95% CI, 0.074-0.954), human epidermal growth factor 2 (HER2) (-) (RR = 0.833; 95% CI, 0.740-0.939) and TNBC (RR = 0.833; 95% CI, 0.636-0.995). Multivariate analysis of external validation confirmed that pretreatment MetS was associated with a lower pCR rate (P = 0.003), and subgroup analysis also confirmed that this relationship had significant statistical differences in ER (-), HER2 (-), and TNBC subgroups. Conclusions: MetS before BCNACT predicted a lower pCR rate. Intervention on MetS status, especially in ER (-), HER2 (-), and TNBC subgroups, is expected to improve the response rate of BCNACT further.

5.
Front Nutr ; 9: 807841, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35237639

RESUMEN

BACKGROUND AND PURPOSE: Hyperglycemia (HG) is associated with increased postoperative complications. This study aims to evaluate the effect of HG during supplemental parenteral nutrition (SPN) on short-term prognosis in non-diabetic patients undergoing gastrectomy for cancer and to analyse the risk factors and prevention methods for HG. METHODS: A total of 359 patients were divided into three groups according to blood glucose (BG) during SPN: normoglycemic patients ( ≤ 125 mg/dL), mild HG (125~200 mg/dL), and severe HG (>200 mg/dL). The effect of BG on postoperative short-term outcomes was analyzed. Multivariate regression was performed to investigate influencing factors for severe HG. The safety and efficacy of insulin addition to total nutrient admixture (TNA) for the prevention and management of HG were assessed by propensity score matching (PSM). In addition, regression analysis was performed in the noninsulin group to investigate the predictive factors of severe HG, and a nomogram was plotted. RESULTS: The postoperative complication rate was 18.9%, but it was significantly higher in patients with severe HG than in mild HG and normoglycemic patients (25.2, 15.0, and 10.0%, respectively, p < 0.05). Multivariate logistic regression analysis showed that anemia, myosteatosis, higher postoperative capillary blood glucose (CBG) before TNA infusion, and insulin in the TNA were independent influencing factors for severe HG. Based on the above factors, 75 pairs of patients (insulin group and non-insulin group) with comparable baseline data were successfully matched by PSM. The HG incidence and the glycemic fluctuation were significantly improved through 1 U insulin/6 g glucose (1/6 scheme) to TNA. A nomogram containing hemoglobin, skeletal muscle radiodensity, pre-SPN CBG, and pTNM stage with good predictive efficacy (C-index: 0.750) was constructed based on the noninsulin group. CONCLUSION: Poor postoperative glycemic control was related to worse outcomes in non-diabetic patients undergoing gastrectomy for cancer. Pre-operative anemia, myosteatosis, and high postoperative CBG before TNA infusion are risk factors for severe HG. Insulin in TNA can improve the blood glucose control of patients. Our proposed nomogram rendered an individualized predictive tool for HG during SPN, which helps screen high-risk patients requiring insulin therapy. Future studies with larger samples are needed to develop a complete insulin application protocol for SPN.

6.
Asia Pac J Clin Nutr ; 31(1): 49-56, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35357103

RESUMEN

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness of insulin addition to the total nutrition admixture (TNA) for glycemic control among patients with gastric cancer (GC) receiving supplementary parenteral nutrition (SPN) after gastrectomy. METHODS AND STUDY DESIGN: A retrospective cohort study was conducted among 208 noncritical ill patients who underwent gastrectomy for GC from 2017 to 2019 at a tertiary teaching hospital in Lanzhou, China. All the included patients received individualized SPN and enteral nutrition treatment after gastrectomy. The patients were randomly divided into insulin and noninsulin groups based on the TNA composition. Blood glucose (BG) measurements, glycemic fluctuation, and hypoglycemia incidence during SPN were compared between the two groups. The postoperative comprehensive complications index (CI) and infections were compared according to insulin regimen and postoperative glycemic status. RESULTS: The mean BG was significantly lower and fluctuated less in the insulin group than in the noninsulin group (p<0.05). One unit of insulin per 6 g of parenteral nutrition glucose addition to TNA did not increase hypoglycemia incidence (p>0.05). Comparing CI and the infection rate, no significance was observed between the insulin and noninsulin groups, but a higher postoperative CI was observed in patients with hyperglycemia than in euglycemic patients (p<0.05). CONCLUSIONS: Appropriate insulin addition to TNA has an overall positive effect on glycemic management in patients with noncritical GC who received SPN after gastrectomy. Postoperative glycemic status was associated with the incidence of relevant complications. Further research is needed for conclusive recommendations.


Asunto(s)
Hiperglucemia , Neoplasias Gástricas , Humanos , Hiperglucemia/epidemiología , Hiperglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Insulina/uso terapéutico , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/cirugía
7.
Probiotics Antimicrob Proteins ; 14(1): 60-71, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33956306

RESUMEN

Gastrointestinal mucositis associated with the use of chemotherapeutic drugs can seriously affect the quality of life of patients. In this study, a probiotic mixture, BIO-THREE, was used to alleviate intestinal damage caused by oxaliplatin in mice and human patients. Kunming mice were injected with 15 mg/kg of oxaliplatin twice, and BIO-THREE tablets were administered to mice for 12 days. Patients with gastric cancer undergoing oxaliplatin treatment took BIO-THREE tablets for 2 weeks. The changes in the composition of fecal microbiota both in patients and mice were analyzed using 16S rRNA high-throughput sequencing. In mice, oxaliplatin caused a drop in body weight and produced lesions in the liver and small intestines. Probiotic therapy successfully mitigated the damage caused by oxaliplatin to the intestinal tract, but it was not very effective for the liver damage and weight loss caused by oxaliplatin. The sequencing of the gut microflora indicated that oxaliplatin treatment increased the abundance of Bacteroidetes and decreased the abundance of Prevotella in mice. After taking probiotics, the feces of mice and human patients both had a higher abundance of Plovitella and a lower abundance of Bacteroides. The increase in Bacteroidetes and decrease in Prevotella in the gut community might be associated with oxaliplatin-induced intestinal damage. Probiotics appeared to be beneficial, decreasing intestinal damage by restoring the abundance of Bacteroidetes and Prevotella.


Asunto(s)
Microbioma Gastrointestinal , Probióticos , Heces , Humanos , Oxaliplatino/efectos adversos , Probióticos/uso terapéutico , Calidad de Vida , ARN Ribosómico 16S/genética
8.
Ear Nose Throat J ; : 1455613211056547, 2021 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-34935547

RESUMEN

As a variant of recurrent inferior laryngeal nerve (RILN), the nonrecurrent inferior laryngeal nerve (NRILN) is closely related to the occurrence of abnormal subclavian artery (ASA). The nonrecurrent inferior laryngeal nerve has been found in patients without arterial abnormalities, which is seen in the coexistence of NRILN and RILN, but it is easily confused with sympathetic-inferior laryngeal anastomosis branch (SILAB). We encountered 2 right NRILN patients without ASA during thyroid surgery. This article summarizes the characteristics of these cases and proposes methods to distinguish the coexistence of NRILN and RILN from SILAB. So far, 11 articles have reported 16 cases of NRILN without arterial abnormalities. In patients without artery abnormality, the vagus nerve could send out a descending branch NRILN at the bifurcation of the carotid artery and enter the larynx after anastomosis with RILN. Adequate dissection of the carotid sheath may avoid confusion with SILAB, and neural monitoring is also expected to provide a reference for the identification.

9.
Cancer Cell Int ; 21(1): 438, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34419048

RESUMEN

BACKGROUND: Gastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer. METHODS: Bioinformatics analysis was employed to clarify the expression patterns of NEK1-NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo. RESULTS: Bioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest. CONCLUSION: NEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.

10.
Sci Robot ; 6(51)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-34043530

RESUMEN

Human skin can sense subtle changes of both normal and shear forces (i.e., self-decoupled) and perceive stimuli with finer resolution than the average spacing between mechanoreceptors (i.e., super-resolved). By contrast, existing tactile sensors for robotic applications are inferior, lacking accurate force decoupling and proper spatial resolution at the same time. Here, we present a soft tactile sensor with self-decoupling and super-resolution abilities by designing a sinusoidally magnetized flexible film (with the thickness ~0.5 millimeters), whose deformation can be detected by a Hall sensor according to the change of magnetic flux densities under external forces. The sensor can accurately measure the normal force and the shear force (demonstrated in one dimension) with a single unit and achieve a 60-fold super-resolved accuracy enhanced by deep learning. By mounting our sensor at the fingertip of a robotic gripper, we show that robots can accomplish challenging tasks such as stably grasping fragile objects under external disturbance and threading a needle via teleoperation. This research provides new insight into tactile sensor design and could be beneficial to various applications in robotics field, such as adaptive grasping, dexterous manipulation, and human-robot interaction.


Asunto(s)
Órganos Artificiales , Mano , Robótica/instrumentación , Piel , Tacto , Materiales Biomiméticos , Módulo de Elasticidad , Elastómeros , Humanos , Aprendizaje Automático , Fenómenos Magnéticos , Fenómenos Mecánicos , Robótica/estadística & datos numéricos , Materiales Inteligentes
11.
J Cancer ; 12(11): 3277-3290, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33976737

RESUMEN

Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN, COL1A1, COL4A1, COL5A2, NOX4, SPARC, HEYL, SPP1, TIMP1, CTHRC1, TREM2, SFRP4, FBXO32, GPX3, KIF4A, and MMP9 genes associated with GC. The EMT-related pathway was the most significantly altered pathway. TREM2 expression was higher in GC cell lines and was remarkably associated with tumor invasion depth, TNM stage, histological grade, histological type, anatomic subdivision, and Helicobacter pylori state. Knockdown of TREM2 expression inhibited the proliferation, migration, and invasion of GC cells as well as the progression of EMT by PI3K/AKT signaling in vitro. In addition, lung metastasis were decreased in vivo. Conclusions: We identified some important genes associated with the progression of GC via public database analysis, explored and verified the effects of proto-oncogene TREM2 on EMT via the PI3K/AKT pathway. TREM2 may be a novel target in the GC therapy.

13.
Front Genet ; 11: 559138, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33304380

RESUMEN

In recent years, the prevalence of obesity and cancer have been rising. Since this poses a serious threat to human health, the relationship between the two has attracted much attention. This study examined whether fat mass and obesity-associated (FTO) genes are linked, taking into account a Genome-wide Association Study (GWAS) that revealed multiple single nucleotide polymorphism sites (SNPs) of the FTO gene, indicating an association between obesity and cancer in different populations. FTO proteins have been proved to participate in adipogenesis and tumorigenesis with post-transcriptional regulation of downstream molecular expression or through the target of the mammalian target protein rapamycin (mTOR). FTO inhibitors have also been found to share anti-obesity and anti-cancer effects in vivo. In this review, we comprehensively discuss the correlation between obesity and cancer by measuring FTO gene polymorphism, as well as the molecular mechanism involved in these diseases, emphasizing FTO as the common genetic basis of obesity and cancer.

14.
J Water Health ; 18(5): 631-653, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33095189

RESUMEN

Quality, safety and potability of repeatedly-boiled water (RBW) and prolonged-boil water (PBW) lead to concern and even misgivings in the public from time to time, especially in China, and other societies have a habit of drinking boiled water, with improvements of living standards and owing to increasing concerns for human health. This phenomenon is mainly attributed to the fact that the conclusions drawn from existing scientific experiments could not respond well to the concerns. In order to make up for this deficiency, tap water was selected to carry out RBW and PBW experiments independently. The quality changes of RBW and PBW show very similar trends that are not as great as might be imagined, and both are impacted by the tap water quality and the physiochemical effects. The dominating physiochemical effects are the water evaporation and the resulting concentration of unreactive components (most dissolved components), which can be easily explained by the existing evaporation-concentration theory. The results show that tap water will be still safe and potable after being frequently boiled or after having undergone prolonged boiling, as long as it satisfies the sanitary standards of drinking water prior to heating. Therefore, there is no need to worry about drinking RBW or PBW in daily life.


Asunto(s)
Agua Potable , Purificación del Agua , China , Agua Potable/análisis , Humanos , Calidad del Agua , Abastecimiento de Agua
15.
Int J Oncol ; 57(4): 881-889, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32945399

RESUMEN

Extracellular vesicles (EVs) enclose a myriad of proteins and nucleic acids that are released in the extracellular milieu of cells through EVs. These secreted molecules serve as signaling factors that can alter the biological characteristics of tumor cells. Several studies have suggested that EVs are associated with tumor proliferation, metastasis and microenvironmental regulation in thyroid carcinoma (TC). The biomolecules in EVs can serve as differential diagnostic biomarkers for TC. Moreover, EVs derived from natural killer (NK) cells can be developed as potential immunotherapeutic agents, since they can actively target and kill tumor cells in TC. Recent years have witnessed a steep rise in the number of TC cases, and thus, accurate diagnosis and novel TC treatment strategies are being actively explored. The present review discusses the recent research investigations on EVs as far as the biological, clinical diagnosis and treatment of primary TC tumors are concerned. In addition, the new opportunities and challenges encountered in the practical applications of EVs in thyroid carcinoma are outlined.


Asunto(s)
Vesículas Extracelulares/genética , Neoplasias de la Tiroides/patología , Animales , Biomarcadores de Tumor/análisis , Progresión de la Enfermedad , Vesículas Extracelulares/metabolismo , Humanos , Transducción de Señal , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/terapia
16.
Curr Drug Metab ; 20(10): 785-798, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31608838

RESUMEN

OBJECTIVES: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. METHODS: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients' clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. RESULTS: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients' Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. CONCLUSION: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.


Asunto(s)
Carcinoma Hepatocelular/genética , Exosomas/genética , Hepatitis B Crónica/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , MicroARNs/sangre , Biomarcadores/análisis , Antígeno Ca-125/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Pronóstico , alfa-Fetoproteínas/análisis
17.
Life Sci ; 232: 116638, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31288013

RESUMEN

AIMS: High-fat diet (HFD)-induced obesity resulting in cholesterol accumulation is one of the common pathogenic factors for lipids metabolic disorders. However, the potential mechanisms about cholesterol accumulation during obesity are still not clearly identified. Bile acids (BAs) as the natural ligands of farnesoid x receptor (Fxr) are demonstrated that can regulate the relevant enzymes and transporters at transcriptional level to determine the cholesterol homeostasis. Here, we explored the underlying mechanisms of hepatic cholesterol accumulation in HFD-induced obesity rats via the BAs-Fxr-enzymes/transporters signaling pathways. MATERIALS AND METHODS: BAs and cholesterol levels as well as mRNA expressions of enzymes, transporters and nuclear receptors involving in cholesterol homeostasis in liver and ileum tissue were evaluated in 4-week HFD-induced obesity rats. KEY FINDINGS: HFD promoted BAs intestine passive absorption to increase the concentrations of BAs especially the chenodeoxycholic acids (CDCAs) in ileum of HFD-induced obesity rats. The increased CDCAs concentrations activated Fxr-Fgf15 pathway in ileum to result in the mRNA expression of Cyp7a1 in liver down-regulation, which inhibited cholesterol metabolizing into primary BAs to contribute to the cholesterol level increase in liver tissue in HFD-induced obesity rats. SIGNIFICANCE: The hepatic cholesterol accumulation should be ascribed to the activation of ileum Fxr-Fgf15 pathway by the increased BAs passive absorption into ileal enterocytes under the condition of rats fed with HFD, which inhibited hepatic Cyp7a1 gene transcription to reduce metabolic elimination of cholesterol. Moreover, these findings are expected to provide a cue for the treatment of cholesterol metabolism disorders in obesity patient.


Asunto(s)
Colesterol 7-alfa-Hidroxilasa/antagonistas & inhibidores , Dieta Alta en Grasa , Factores de Crecimiento de Fibroblastos/metabolismo , Íleon/metabolismo , Hígado/metabolismo , Obesidad/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Animales , Ácidos y Sales Biliares/metabolismo , Células CACO-2 , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilasa/metabolismo , Humanos , Masculino , Proteínas de Transporte de Membrana/metabolismo , Obesidad/enzimología , Ratas , Ratas Wistar , Transducción de Señal
18.
J Cell Biochem ; 120(11): 18714-18723, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31218757

RESUMEN

Gastric cancer has become the third most common cancer around the world. In patients with gastric cancer, the 5-year survival rate is still low. However, the mechanism underlying gastric cancer remains largely unknown. As a glycolytic enzyme, enolase 1 (ENO1) is widely expressed in most tissues. The functions of ENO1 have been reported in various types of cancer. Here in this study, we identified that ENO1 promoted the growth of gastric cancer cells through diverse mechanisms. Our immunohistochemical, bioinformatic and Western blot data showed that ENO1 was significantly overexpressed in human gastric cancer cell lines and tissues. The survival analysis revealed that ENO1 overexpression predicted poor survival in the patients suffering gastric cancer. Knockdown of ENO1 expression repressed the rate of proliferation and capacity of colony formation in two human gastric cancer cell lines (MGC-803 and MKN-45). In addition, knockdown of the expression of ENO1 led to the arrest of the cell cycle at the G1 phase and promoted the apoptosis of MKN-45 and MGC-803 cells. The further microarray and bioinformatic analysis revealed that ENO1 regulated the expression of diverse genes, many of which are involved in the progress of cancer. Taken together, our data demonstrated that ENO1 was an oncogene-like factor and might serve as a promising target for the treatment of human gastric cancer.


Asunto(s)
Biomarcadores de Tumor/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Fosfopiruvato Hidratasa/genética , Neoplasias Gástricas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/genética , Biomarcadores de Tumor/metabolismo , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proteínas de Unión al ADN/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fosfopiruvato Hidratasa/metabolismo , Interferencia de ARN , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Proteínas Supresoras de Tumor/metabolismo , Adulto Joven
19.
Life Sci ; 229: 80-92, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31095947

RESUMEN

PURPOSE: Bile acids (BAs) as a kind of endogenous and signaling molecules altered under the circumstance of T2DM, which could impact on the relevant pathways to further affect the glucose metabolism and insulin secretion and might be associated with the T2DM development and restoration. However, the potential mechanisms still need more various and multifaceted studies. Here, we explored the alterations of BAs features and their mechanisms, and discussed the potential effects of the altered BAs on the glucose metabolic disorder via the relevant signaling pathways. MAIN METHODS: The high-fat diet (HFD) feeding combining with injection of low-dose streptozotocin (STZ) was employed for inducing the T2DM rat model. Based on that, we investigated the alterations of the concentrations and compositions of BAs and their mechanisms, and explored the effects of the altered BAs on the glucose metabolic disorder via farnesoid X receptor (Fxr) and G protein-coupled bile acid receptor (Tgr5)-mediated pathways. KEY FINDINGS: In rats with T2DM, the BAs in rats with T2DM exhibited characteristic alterations, especially the increased ratio of 12α-OH to non-12α-OH BAs in serum, which could be ascribed to the up-regulated Cyp8b1 mRNA expression ratio in the liver. Moreover, Additionally, the altered BAs had negative effects on glucose metabolic disorder via inhibiting the Trg5/Fxr-mediated pathways in colon, liver and pancreas in rats with T2DM. SIGNIFICANCE: BAs in rats with T2DM exhibited the characteristic alterations, which could provide a cue for searching biomarkers of the T2DM diagnosis, and the altered BAs might aggravate the glucose metabolic disorder.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Glucosa/metabolismo , Resistencia a la Insulina , Estreptozocina/toxicidad , Animales , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo de los Lípidos , Masculino , Ratas , Ratas Wistar , Transducción de Señal
20.
Ann Transl Med ; 7(6): 124, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31032279

RESUMEN

BACKGROUND: Gastric cancer has been the second cause of cancer death worldwide. Chemical comprehensive treatment programs primarily were the main therapy method with modest efficacy to gastric cancer. Traditional Chinese medicine (TCM) has been reported to alleviate adverse events induced by chemotherapy, but has not yet developed clinical trials to test and needs scientific evidence for making policy. Single-patient (N-of-1) trials might be an eligible study design for TCM since it well represented the individualized treatment philosophy of TCM. The aim of this study is to obtain information necessary to design a more series trial. METHODS: Individuals who underwent gastrectomy were included. Each patient suffered 3-week standard chemotherapy and 3-day treatment periods (decoction with Astragalus mongholicus and Semen Cuscutae or placebo: decoction without Astragalus mongholicus and Semen Cuscutae). Each trial lasted up to a maximum of 30 weeks or a minimum of 20 weeks. Staffs and participants were blinded to the randomization. This study was approved by Ethics Committee of First Hospital, Lanzhou University in November, 2014. RESULTS: From August, 2014 to March, 2015, 6 participants were included. There were 16 cycles compared between intervention and control decoction (2.28, 95% CI: 1.24-5.47), P<0.0001. The quality of life (QoL) score after the trial was reported is a little higher than before, t=3.87, P=0.01. Two participants reported symptoms had improved after taken trial decoction. CONCLUSIONS: This is the first N-of-1 trials of testing the effectiveness of TCM decoction on alleviative treatment to gastric cancer. The feasibility study will help to develop a practical design for the more series trial.

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