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1.
J Nanobiotechnology ; 19(1): 31, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482834

RESUMO

BACKGROUND: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. RESULTS: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. CONCLUSIONS: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.


Assuntos
Acetilcolinesterase/genética , Técnicas de Transferência de Genes , Lipossomos/química , Neoplasias Hepáticas/terapia , Plasmídeos/genética , Transferrina/química , Animais , Linhagem Celular Tumoral , Feminino , Terapia Genética , Humanos , Neoplasias Hepáticas/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Plasmídeos/administração & dosagem , Plasmídeos/uso terapêutico , Transfecção
2.
Artigo em Inglês | MEDLINE | ID: mdl-32908558

RESUMO

PURPOSE: This study aimed to investigate the effects of different concentrations of Yiqi Xingnao (YQXN) oral liquid on cerebral ischemia/reperfusion (I/R) injury in rats and YQXN's related mechanisms. METHODS: Rats were pretreated with 3 mL/kg, 6 mL/kg, and 12 mL/kg YQXN and Naoxuekang capsule (NXK). Afterwards, cerebral I/R model rats were established by a middle cerebral artery occlusion surgery. Neurological deficits, histopathology, and cerebral infarction volume were used to evaluate the effects of YQXN. Evans blue and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were utilized to determine the blood-brain barrier permeability and cell apoptosis, respectively. The expression of VEGF and Bcl-2 was analyzed by real-time quantification PCR (RT-qPCR) and western blot. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured using corresponding assay kits. RESULTS: The rats pretreated with YQXN had improved neurological deficits, reduced infarct volume and blood-brain barrier permeability, and ameliorated ischemia-induced morphology change in injured brain tissues. TUNEL staining results showed that different concentrations of YQXN inhibited cell apoptosis of neurocytes in I/R rats. Besides, RT-qPCR and western blot analyses indicated that the expression levels of VEGF and Bcl-2 were significantly upregulated by YQXN compared with the I/R group (P < 0.05). Additionally, rats in the I/R group had lower SOD activity and higher MDA content than those in the sham-operated group, while their levels were recovered by YQXN (P < 0.05). CONCLUSION: YQXN could alleviate cerebral I/R injury by suppressing blood-brain barrier permeability, neuron apoptosis, and oxidative stress, promoting angiogenesis.

3.
Int J Nanomedicine ; 15: 4933-4941, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764926

RESUMO

PURPOSE: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. MATERIALS AND METHODS: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. RESULTS: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p>0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p<0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p<0.05. CONCLUSION: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer.


Assuntos
Fluorescência , Lipossomos/química , Neoplasias Hepáticas/diagnóstico , Mutação , Polímeros/química , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismo , Adulto , Área Sob a Curva , Automação , Biomarcadores Tumorais/sangue , Feminino , Humanos , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Imãs/química , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
4.
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.

5.
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.

6.
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
7.
J Cell Physiol ; 234(8): 13867-13877, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30697724

RESUMO

We previously reported that Xiaotan Sanjie (XTSJ) decoction can prevent the progression of gastric cancer in vitro and in vivo. Pinelliae rhizome (PR), one component of XTSJ decoction, has an inhibitory effect on the growth and proliferation of tumor cells. The present study investigated the underlying mechanisms of action of PR. Using the human papillary thyroid cancer cell lines, TPC-1 and BCPAP, we found that XTSJ decoction and PR alone decreased cell viability to a similar extent in both cell lines, whereas treatment with XTJS decoction without PR [PR (-)] had a lesser effect. PR treatment inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in a dose-dependent manner. To investigate the role of Nrf2 in the PR-mediated effects of XTSJ, knockdown of Nrf2 in the tumor cell lines using Nrf2 siRNA (siNrf2) was performed and transfected cells were treated with PR. Silencing of Nrf2 amplified the effects on autophagy, cell viability, apoptosis, and colony formation. Similar results were obtained following treatment with the autophagy inhibitor 3-methyladenine (3-MA). Furthermore, treatment with PR, siNrf2, and/or 3-MA inhibited the MAPK pathway, and analysis of the MAPK pathway components confirmed the role of this pathway in the PR-mediated cellular effects. In mice implanted with siNrf2-transfected cells, the effects of PR were amplified. Taken together, these findings indicate that PR is critical for the inhibitory effects of XTSJ decoction on tumor cell viability and that downregulation of Nrf2 promotes the antitumor effects of PR on papillary thyroid cancer cells.


Assuntos
Antineoplásicos/uso terapêutico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Pinellia/química , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
8.
Oncol Lett ; 17(2): 1914-1920, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675255

RESUMO

High-fat diets (HFDs) are a risk factor for colorectal cancer. The present study investigated whether HFDs increase colon cancer metastasis in BALB/c mice. A total of 40 BALB/c mice were divided into four groups, including the tumor, tumor-HFD, HFD and control groups. After 3 weeks, the tumor weights and metastases were observed. The serum levels of triglyceride, total cholesterol, lapin, interleukin-6 (IL-6) and tumor necrosis factor were analyzed using ELISA. The CD34, vascular endothelial growth factor (VEGF) and angiotensin 2 (ANG2) protein and mRNA levels in tumor tissues were analyzed with immunohistochemistry and reverse transcription-polymerase chain reaction. The metastasis frequency increased in the tumor-HFD group. However, there was no difference in the mean tumor weight between the tumor-HFD and tumor groups. The serum cholesterol levels were increased in the tumor-HFD and HFD groups compared with the control group. The levels of serum IL-6 and tumor necrosis factor-α were increased in the tumor-HFD group compared with other groups. The CD34 protein level, and VEGF protein and mRNA levels were increased in the tumor-HFD group compared with the tumor group. No difference was identified between the ANG2 protein and mRNA levels in of the two groups. It was concluded that HFD increased the serum level of cholesterol and cytokines, and potentially induced tumor angiogenesis, promoting transplanted orthotopic colon tumor metastasis in BALB/c mice.

9.
J Integr Med ; 15(6): 469-475, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29103417

RESUMO

OBJECTIVE: Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS: In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome. RESULTS: The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ2 = 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival. CONCLUSION: This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.


Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Integrativa , Medicina Tradicional Chinesa , Fitoterapia , Neoplasias Gástricas/tratamento farmacológico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida
10.
J Ethnopharmacol ; 172: 155-61, 2015 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-26038151

RESUMO

ETHONOPHARMACOLOGICAL RELEVANCE: Cancer is considered to be the second leading cause of human death. It is unsatisfactory that in the past decades, the treatment for cancer has not progressed as fast as it was expected, as only 50% of newly diagnosed patients could be cured even today. The development of cancer is a multifactorial process, involving tumor cells themselves, the interactions between tumor cells and their microenvironments, as well as the interactions between tumor cells and the host's immunity. Focusing on any single goal may bring limited benefits. AIM AND METHODS OF THE STUDY: Phlegm-eliminating herbs, which can reduce phlegm and eliminate pathological metabolites, are commonly used to treat cancer in China. However, the underlying molecular targets and efficacy of herbal medicines in cancer treatment still remain unclear. In this study, we reviewed the potential anticancer mechanisms of some phlegm-eliminating herbs and their active ingredients from the articles through such scientific databases as MEDLINE, PubMed, and Google Scholar. RESULTS: We found that the anticancer mechanisms of phlegm-eliminating herbs and ingredients include inducing apoptosis, anti-proliferation, preventing tumor invasion and metastasis, and reducing resistance to chemotherapy. In addition, some phlegm-eliminating herbs and their ingredients have anti-inflammatory and anti-metabolic syndrome effects. CONCLUSIONS: We suggest that the phlegm-eliminating herbs and ingredients are potential candidates for anticancer treatment and cancer prevention by playing a comprehensive role.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Muco/efeitos dos fármacos , Fitoterapia/métodos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Etnofarmacologia , Humanos , Síndrome Metabólica/tratamento farmacológico
11.
Chin J Integr Med ; 21(8): 579-86, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25399306

RESUMO

OBJECTIVE: To evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients. METHODS: This randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores. RESULTS: Using time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01). CONCLUSION: Additional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Qualidade de Vida , Neoplasias Gástricas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , Placebos , Neoplasias Gástricas/fisiopatologia , Adulto Jovem
12.
Tumour Biol ; 35(9): 8875-81, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24894674

RESUMO

Increasing evidence indicated that insulin-like growth factor binding protein 7 (IGFBP7) was regarded as a potential tumor suppressor in various human cancers, but its role in gastric cancer is still largely unknown. In the present study, we performed a retrospective study which includes 247 gastric cancer patients. Among them, the IGFBP7 expression was detected by qRT-PCR in 138 cases of gastric cancer and adjacent non-tumor tissues and was further correlated with the expression of p53, Ki-67, and the clinicopathologic features. The results indicated that both IGFBP7 mRNA and protein in gastric cancer tissues were significantly lower than those in the adjacent non-tumor tissues. Additionally, the expression of IGFBP7 was correlated with the depth of invasion, lymph node metastasis, and TNM stage. Interestingly, the expression of IGFBP7 was negatively associated with Ki-67 (r = -0.227, P < 0.001) but positively associated with p53 (r = 0.140, P = 0.028). Univariate analysis showed that low expression of IGFBP7 was associated with poor prognosis (P < 0.001), and multivariate analysis showed that IGFBP7 (HR = 1.87; 95 % CI 1.65-2.17), distant metastasis (HR = 2.68; 95 % CI 1.58-4.56), and tumor size (HR = 1.45; 95 % CI 0.90-2.32) were independent prognostic factors for gastric cancer patients. These results demonstrated that IGFBP7 was downregulated in gastric cancer, and its low expression was potentially correlated with increased cancer cell proliferation and could be used to predicate poor prognosis in these patients.


Assuntos
Mucosa Gástrica/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Neoplasias Gástricas/genética , Proliferação de Células , Regulação para Baixo , Seguimentos , Humanos , Imuno-Histoquímica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estômago/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteína Supressora de Tumor p53/metabolismo
13.
PLoS One ; 9(3): e90547, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24618826

RESUMO

BACKGROUND: Increasing evidence indicated plasma D-dimer could be regarded as a marker in cancers, however, its role in gastric cancer is still largely unknown. METHODS: Plasma D-dimer levels were measured by enzyme linked fluorescent immunoassays and evaluated by receiver operating characteristic (ROC) curves for peritoneal dissemination in gastric cancer and healthy subjects. The overall survival (OS) characteristics were determined using Kaplan-Meier and Cox regression analyses. RESULTS: The average of the plasma D-dimer levels for gastric cancer patients was significantly higher than the healthy subjects. A Spearman correlation analysis showed that plasma D-dimer levels correlated with the depth of invasion, lymph node metastasis, peritoneal dissemination, distant metastasis, tumor size and TNM stage. The mean plasma D-dimer level was 2.20 ± 1.51 µg/mL in peritoneal dissemination patients and 1.01 ± 0.79 µg/mL in non-peritoneal dissemination patients (P<0.001). Additionally, the mean plasma D-dimer concentration in patients alive at the final follow-up evaluation was 0.79 ± 0.72 µg/mL,which was significantly lower than the amounts determined for the deceased patients (1.36 ± 1.13 µg/mL) (P<0.001). The AUC of D-dimer was 0.833 (95%CI: 0.780-0.885). At a cut-off value of 1.465 µg/mL, the D-dimer measurement had a sensitivity of 78.00%, a specificity of 83.76% and an accuracy of 82.59%. The median OS was 48.10 months (95% CI: 43.88-52.31) in patients with plasma D-dimer levels less than 1.465 µg/mL and 22.39 months (95% CI: 16.95-27.82) in patients with plasma D-dimer levels exceeding 1.465 µg/mL (log-rank test, P<0.001). Importantly, plasma D-dimer levels exceeding 1.465 µg/mL were significantly associated with poor OS, as determined using a multivariate Cox regression analysis (hazard ratio [HR], 2.28; 95%CI: 1.36-3.81; P = 0.002). CONCLUSIONS: Plasma D-dimer levels are increased in gastric cancer patients and may be a valuable biomarker for peritoneal dissemination, with high D-dimer levels predicting poor outcomes for gastric cancer patients.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Idoso , Biomarcadores , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/secundário , Prognóstico , Curva ROC , Neoplasias Gástricas/diagnóstico , Carga Tumoral
14.
PLoS One ; 8(10): e77821, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24147084

RESUMO

BACKGROUND AND AIMS: To identify and validate N-glycan biomarkers in gastric cancer (GC) and to elucidate their underlying molecular mechanism of action. METHODS: In total, 347 individuals, including patients with GC (gastric cancer) or atrophic gastritis and healthy controls, were randomly divided into a training group (n=287) and a retrospective validation group (n=60). Serum N-glycan profiling was achieved with DNA sequencer-assisted/fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on the N-glycan profiles using logistic stepwise regression. The diagnostic performance of each model was assessed in retrospective, prospective (n=60), and follow-up (n=40) cohorts. Lectin blotting was performed to determine total core-fucosylation, and the expression of genes involved in core-fucosylation in GC was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: We identified at least 9 N-glycan structures (peaks) and the levels of core fucose residues and fucosyltransferase were significantly decreased in GC. Two diagnostic models, designated GCglycoA and GCglycoB, were constructed to differentiate GC from control and atrophic gastritis. The areas under the receiver operating characteristic (ROC) curves (AUC) for both GCglycoA and GCglycoB were higher than those for CEA, CA19-9, CA125 and CA72-4. Compared with CEA, CA19-9, CA125 and CA72-4, the sensitivity of GCglycoA increased 29.66%, 37.28%, 56.78% and 61.86%, respectively, and the accuracy increased 10.62%, 16.82%, 25.67% and 28.76%, respectively. For GCglycoB, the sensitivity increased 27.97%, 35.59%, 55.09% and 60.17% and the accuracy increased 21.26%, 24.64%, 31.40% and 34.30% compared with CEA, CA19-9, CA125 and CA72-4, respectively. After curative surgery, the core fucosylated peak (peak 3) and the total core fucosylated N-glycans (sumfuc) were reversed. CONCLUSIONS: The results indicated that the diagnostic models based on N-glycan markers are valuable and noninvasive alternatives for identifying GC. We concluded that decreased core-fucosylation in both tissue and serum from GC patients may result from the decreased expression of fucosyltransferase.


Assuntos
Biomarcadores/sangue , Polissacarídeos/sangue , Neoplasias Gástricas/sangue , Feminino , Gastrite Atrófica/sangue , Gastrite Atrófica/metabolismo , Humanos , Técnicas In Vitro , Masculino , Memória Episódica , Pessoa de Meia-Idade , Polissacarídeos/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo
15.
Chin J Integr Med ; 18(5): 350-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22549391

RESUMO

OBJECTIVE: To extract tumor interstitial fluid (TIF) from MKN-45 gastric cancer which is similar to "muddy phlegm" in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid (MKN-45 TIF) intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor (VEGF), kinase insert domain containing receptor (KDR), epithelial-cadherin (E-cad), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1) and telomerase genes and proteins in primary tumor tissue. METHODS: An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups: the simple tumor-bearing group (model group), the normal saline (NS) via tail vein injection (i.v.) group (NS i.v. group), MKN-45 TIF i.v. group (TIF i.v. group), NS intraperitoneal injection (i.p.) group (NS i.p. group), and MKN-45 TIF i.p. group (TIF i.p. group). The TIF and NS intervention groups received injection (i.p. or i.v.) of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. RESULTS: There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. CONCLUSIONS: TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of "tumor-phlegm microenvironment".


Assuntos
Líquido Extracelular/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundário , Microambiente Tumoral/fisiologia , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Telomerase/genética , Telomerase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Zhong Xi Yi Jie He Xue Bao ; 8(7): 629-35, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20619138

RESUMO

OBJECTIVE: To explore the relationship between expressions of estrogen (ER) and progesterone (PR) receptors and syndromes of traditional Chinese medicine (TCM) in gastric carcinoma and to establish prognostic indicators for gastric carcinoma. METHODS: A total of 72 patients with gastric carcinoma were divided into six groups according to TCM syndrome differentiation. Specimens were collected after operation and ER and PR protein expressions were detected by EnVision immunohistochemical method. RESULTS: The common syndromes in female patients with gastric carcinoma were disharmony between liver and stomach, yin impairment due to stomach heat, and insufficiency of both qi and blood; while in males, interior retention of stagnant toxin, interior retention of phlegm and dampness, and deficiency-cold in spleen and stomach were common. Different TCM syndromes were related with gender (P<0.01), pathology (P<0.01), cell differentiation (P<0.05), infiltration depth (P<0.01), lymphaden metastasis (P<0.05), distant metastasis (P<0.05), and TNM stage (P<0.01). Deficiency and excess syndromes were associated with gender (P<0.05), pathology (P<0.05), tumor location (P<0.01) and TNM stage (P<0.05). The deficiency syndromes were common in female patients. The total positive rates of ER and PR expressions were 8.33% and 37.5% respectively. There was a significant difference in PR expression among different TCM syndromes (P<0.01). PR expression was significantly higher in the syndrome of yin deficiency due to stomach heat than in the other syndromes. The PR expressions in deficiency syndromes were significantly higher than those in excess syndromes (P<0.01). No correlation was found between ER expression and different TCM syndromes. CONCLUSION: There is a correlation between PR expression and different TCM syndromes in gastric carcinoma.


Assuntos
Medicina Tradicional Chinesa , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Zhong Xi Yi Jie He Xue Bao ; 8(4): 332-40, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20388473

RESUMO

OBJECTIVE: The present study is a summary of syndrome types of gastric cancer in order of priority based on clinical practical situations, routine clinical syndrome differentiation and a large-sample clinical survey in 767 patients with gastric cancer. METHODS: Based on the six-type classification of gastric cancer in a previous study, a bedside syndrome differentiation diagnosis was made simultaneously by two attending doctors of traditional Chinese medicine (TCM to avoid possible diagnostic bias. A clinical differentiation survey form designed under the direction of epidemiologists was filled out by patients with gastric cancer in multiple centers, and the results were digitally valued and statistically analyzed. RESULTS: The symptoms and signs in each syndrome type of gastric cancer were ranked in order of priority as follows: distended pain, stringy pulse, eructation, mood-related pain, susceptibility to anger, acid regurgitation, hiccup, fullness sensation or distension after eating just a little, dizziness, thin pulse, abdominal enlargement, obstruction sensation after eating, moving pain, and uneven pulse in disharmony between liver and stomach; dark red tongue with little fur or a smooth surface, burning pain, rapid pulse, associated burning heat in anus, dry mouth, fissured tongue, thin pulse, tidal fever in the afternoon, nausea and vomiting, and night sweating in impairment of yin due to stomach heat; slender tongue fur, obstruction after eating, slow pulse, moderate pulse, rapid and irregular pulse, normal mood, abdominal pain, diarrhea, cold extremities, lower-extremity edema, cold intolerance, pale complexion, dizziness, emaciation, hiccup, silence, nausea, uneven pulse, acid regurgitation, fullness sensation or distension after eating just a little, vomiting, and constipation in deficiency-cold in spleen and stomach; uneven pulse, stabbing pain, tortuous sublingual vein, blue or purplish tongue, fixed pain, tarry stool or dark red stool, vomiting of dark red fluid, pale complexion, dry mouth without desire to drink, stringy pulse, white tongue fur, nausea, thin tongue fur, colic pain, hiccup, dizziness, acid regurgitation, bitter taste in mouth, slow pulse, rapid and irregular pulse, thin pulse, and pain relief by pressing in interior retention of toxin stagnation; slippery pulse, greasy and thick tongue fur, dry mouth without desire to drink, vomiting of bilious fluid, nausea, bitter taste in mouth, fullness sensation or distension after eating just a little, colic pain, and hiccup in stagnation of phlegm-dampness; abdominal pain relief by pressing, map-like tongue, thin pulse, weakness, yellowish complexion, dizziness, spontaneous sweating, fissured tongue, epigastric discomfort, night sweating, emaciation, cold intolerance, constipation, nausea, and dry tongue in deficiency of both qi and blood. CONCLUSION: The summarized syndrome types of gastric cancer from this study are consistent with the clinical situations and would prove to be more referential for TCM syndrome differentiation diagnosis and treatment of gastric cancer.


Assuntos
Medicina Tradicional Chinesa/métodos , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/classificação , Adulto Jovem
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