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The high mortality of colorectal cancer (CRC) patients and the limitations of conventional tumor-node-metastasis (TNM) stage emphasized the necessity of exploring hub genes closely related to carcinogenesis and prognosis in CRC. The study is aimed at identifying hub genes associated with carcinogenesis and prognosis for CRC. We identified and validated 212 differentially expressed genes (DEGs) from six Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA) database. We investigated functional enrichment analysis for DEGs. The protein-protein interaction (PPI) network was constructed, and hub modules and genes in CRC carcinogenesis were extracted. A prognostic signature was developed and validated based on Cox proportional hazards regression analysis. The DEGs mainly regulated biological processes covering response to stimulus, metabolic process, and affected molecular functions containing protein binding and catalytic activity. The DEGs played important roles in CRC-related pathways involving in preneoplastic lesions, carcinogenesis, metastasis, and poor prognosis. Hub genes closely related to CRC carcinogenesis were extracted including six genes in model 1 (CXCL1, CXCL3, CXCL8, CXCL11, NMU, and PPBP) and two genes and Metallothioneins (MTs) in model 2 (SLC26A3 and SLC30A10). Among them, CXCL8 was also related to prognosis. An eight-gene signature was proposed comprising AMH, WBSCR28, SFTA2, MYH2, POU4F1, SIX4, PGPEP1L, and PAX5. The study identified hub genes in CRC carcinogenesis and proposed an eight-gene signature with good reproducibility and robustness at the molecular level for CRC, which might provide directive significance for treatment selection and survival prediction.
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Neoplasias Colorretais/etiologia , Biologia Computacional , Carcinogênese , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de ProteínasRESUMO
BACKGROUND The aim of this study was to elucidate the involvement of cPLA2-AA-COX-2 pathway factors and their potential role in lung cancer early diagnosis and prognosis. MATERIAL AND METHODS We selected 80 lung cancer patients as the cancer group, and 30 normal patients were selected as the normal group. Serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 were measured, and mRNA levels of COX-2, cPLA2, COX-1, and mPGES in serum were determined. Spearman's P-test was used to analyze the correlation between expression of PGI2 and mPGES in serum and the clinical characteristics of these lung cancer patients. The factors affecting the prognosis lung cancer were analyzed by COX regression model. RESULTS The serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 in the cancer patient group were significantly higher (p<0.05) than in the normal group; after treatment, the serum contents of these factors were significantly decreased (p<0.05). However, distant metastasis had a significant effect on serum contents of mPGES and PGI2 (p<0.05), but not on the other factors. The mRNA levels of COX-2, cPLA2, COX-1, and mPGES in cancer patients were significantly higher than in normal patients. In addition, the 5-year survival rate of patients with high expression of mPGES and/or PGI2 was lower than that of the low expression group. Cox regression analysis showed that the expression of mPGES and PGI2 had statistical significance in predicting the prognosis of lung cancer. CONCLUSIONS The cPLA2-AA-COX-2 pathway is closely associated with lung cancer. These findings are important for clinical diagnosis of lung cancer.
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Ácido Araquidônico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Neoplasias Pulmonares/metabolismo , Fosfolipases A2 Citosólicas/metabolismo , Adulto , Idoso , Ácido Araquidônico/sangue , Ácido Araquidônico/genética , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/genética , Citosol/metabolismo , Dinoprostona/metabolismo , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Oxirredutases Intramoleculares/metabolismo , Isoenzimas , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Fosfolipases A2 Citosólicas/sangue , Fosfolipases A2 Citosólicas/genética , Prognóstico , Prostaglandina-E Sintases/genética , Prostaglandina-E Sintases/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/genéticaRESUMO
AIMS: This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism. MATERIALS AND METHODS: HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay. The effects of HOXB13 and FTO on proliferation, invasion, and migration of GC cells were studied using EdU and Transwell assays. KEY FINDINGS: HOXB13 and FTO expression was abnormally high in GC tissues and cell lines, with no significant correlation between HOXB13 and FTO expression and the prognosis of GC patients. Inhibiting FTO expression in GC cells decreased HOXB13 methylation and upregulated HOXB13 expression. Inhibiting HOXB13 and FTO expression suppressed GC cell proliferation, migration, and invasion. Decreased HOXB13 expression suppressed PI3K/AKT/mTOR signaling pathway activity, while atypical HOXB13 expression promoted it. A probable downstream target of HOXB13 was insulin-like growth factor 1 receptor (IGF-1R); a decrease in IGF-1R relieved GC cell migration, invasion, and proliferation and inhibited PI3K/AKT/mTOR signaling pathway activity promoted by atypical HOXB13 expression. SIGNIFICANCE: HOXB13 and FTO expression is elevated in GC. FTO suppresses HOXB13 methylation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R. HOXB13 and associated signaling pathways can be effective targets for GC therapy.
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Perfilação da Expressão Gênica , Proteínas de Homeodomínio/fisiologia , Receptor IGF Tipo 1/metabolismo , Neoplasias Gástricas/metabolismo , Tecido Adiposo/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Imunoprecipitação , Metiltransferases/metabolismo , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Previous studies revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis and progression of several types of human cancer. However the role of DEPDC1 in gastric cancer has not been studied. OBJECTIVE: The objective of this study was to study the expression and pathophysiological function of DEPDC1 in gastric cancer. METHODS: DEPDC1 expression in gastric adenocarcinoma cells was examined with Western blot and qRT-PCR. Clinical pathological features of patients were determined by immunohistochemistry. The effect of DEPDC1 expression on cell proliferation was studied by in vitro cell proliferation assay; and cell cycle influence was assessed by flow cytometry. Survival curves were plotted using Kaplan-Meier. RESULTS: DEPDC1 was overexpressed in gastric adenocarcinoma tissues compared with the paired adjacent normal gastric tissues, in accordance with mRNA level downloaded from GEPIA database. DEPDC1 expression level was significantly associated with cancer metastasis and differentiation. DEPDC1 upregulation caused cell cycle accelerating from G1 to S phase, and it was correlated with poorer overall survival. CONCLUSION: Therefore, DEPDC1 upregulation in gastric adenocarcinoma is associated with tumor development and poor clinical outcomes of the patients, implying DEPDC1 might be a potential therapeutic target against gastric cancer.
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Proteínas Ativadoras de GTPase/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/genética , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/fisiopatologia , Transfecção , Regulação para CimaRESUMO
Since the herb pair Huang Lian-Gan Jiang (HL-GJ) was put forward as conventional compatibility for cold-heat regulation in the middle energizer in the theory of Traditional Chinese Medicine (TCM), their therapeutic effects were observed on the prevention and treatment of intestinal inflammation and tumors including colorectal cancer (CRC). However, the active compounds, crucial targets, and related pathways of HL-GJ against CRC remained unclear. The purpose of this research was to establish a comprehensive and systemic approach that could identify the active compounds, excavate crucial targets, and reveal anti-CRC mechanisms of HL-GJ against CRC based on network pharmacology. We used methods including chemical compound screening based on absorption, distribution, metabolism, and excretion (ADME), compound target prediction, CRC target collection, network construction and analysis, Gene Ontology (GO), and pathway analysis. In this study, eight main active compounds of HL-GJ were identified, including Gingerenone C, Isogingerenone B, 5,8-dihydroxy-2-(2-phenylethyl) Chromone, 2,3,4-trihydroxy-benzenepropanoic acid, 3,4-dihydroxyphenylethyl Alcohol Glucoside, 3-carboxy-4-hydroxy-phenoxy Glucoside, Moupinamide, and Obaculactone. HRAS, KRAS, PIK3CA, PDE5A, PPARG, TGFBR1, and TGFBR2 were identified as crucial targets of HL-GJ against CRC. There were mainly 500 biological processes and 70 molecular functions regulated during HL-GJ against CRC (P < 0.001). There were mainly 162 signaling pathways contributing to therapeutic effects (P < 0.001), the top 10 of which included DAP12 signaling, signaling by PDGF, signaling by EGFR, NGF signaling via TRKA from the plasma membrane, signaling by NGF, downstream signal transduction, DAP12 interactions, signaling by VEGF, signaling by FGFR3, and signaling by FGFR4. The study established a comprehensive and systematic paradigm to understand the pharmacological mechanisms of multiherb compatibility such as an herb pair, which might accelerate the development and modernization of TCM.
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DEP domain containing 1 (DEPDC1) is a novel tumor-associated gene, which is aberrantly expressed in multiple types of cancer and involves in tumorigenesis and cancer progression. Here, we examined the functional involvement and underlying mechanism of DEPDC1 in breast cancer. In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation indicated DEPDC1's ability of promoting breast cancer cells migration and invasion. In addition, we discovered that DEPDC1 caused hyper-activation of PI3K/AKT/mTOR signaling in breast cancer cells. Therefore, the increased DEPDC1 expression in breast cancer is correlated with disease progression and poor survival, which suggested that DEPDC1 might be a potential therapeutic target against this disease.
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OBJECTIVE: To evaluate the effect of Shen-reinforcing and qi-supplementing (SRQS) drugs on some ingredients of neuro-endocrine-immune (NEI) network in asthma rat model. METHODS: Asthma model was established by ovalbumin sensitization and long-term excitation. Forty healthy Brown Norway rats of clean grade were randomly divided into 4 groups by randomized digital table, the normal control group and the three treated groups treated by low, moderate and high dose of SRQS drugs respectively. Blood content of adrenocorticotrophic hormone (ACTH) was detected by RIA; interleukin-6 (IL-6) and corticosterone were determined by ELISA; and the mRNA expresion of corticosteroid release hormone (CRH) in hypothalamus was tested by Realtime-PCR. RESULTS: Eosinophile inflammation was shown in the pathology of asthma model rats, and also shown a multiple level hypothalamic-pituitary-adrenal axis (HPA axis) disorder at the repeated attack of asthma. After treatment, levels of ACTH and CRH mRNA expression in the treated groups were significantly higher than those in the control group (P <0.05), but the corticosterone only showed a rising tendency. Level of IL-6 increased during the episode, showing a significant negative correlation with ACTH (r = - 0.325, P = 0.043), and had somewhat reduction after SRQS treatment. CONCLUSION: SRQS drugs could improve the function of HPH axis independent of IL-6, suggesting that the action is possibly targeted on the neuro-endocrine axis, which might be the hypothalamus.
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Asma/tratamento farmacológico , Hipotálamo/efeitos dos fármacos , Interleucina-6/imunologia , Rim/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/imunologia , Qi , Animais , Asma/genética , Asma/imunologia , Asma/fisiopatologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Humanos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Interleucina-6/genética , Rim/fisiopatologia , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Distribuição Aleatória , RatosRESUMO
OBJECTIVE: To investigate the efficacy of cytokine-induced killer cell-based immunotherapies in patients with advanced malignant solid tumors and the difference in clinical efficiency among 3 kinds of cytokine-induced killer cell-based immunotherapies. METHODS: One hundred forty-six cases with advanced solid tumor, 230 cycles of cytokine-induced killer cell-based immunotherapies, were involved in this study. T-lymphocyte subsets, carcinoembryonic antigen, and adverse reactions were recorded. RESULTS: CD3+ T lymphocyte, Th, NKT, and Th/Tc were increased after cytokine-induced killer cell-based treatment, from 55.67 ± 3.64 to 84.12 ± 5.15, 26.56 ± 4.47 to 42.76 ± 3.68, 1.82 ± 0.58 to 7.08 ± 0.92, 0.79 ± 3.64 to 1.35 ± 0.20, respectively ( P < .001). Carcinoembryonic antigen was decreased from 398.39 ± 219.16 to 127.26 ± 153.41 ( P < .001). Difference values were greater than 0 ( P < .001). Difference value of carcinoembryonic antigen was obviously less than 0 ( P < .001). There was no obvious difference in all variations between cytokine-induced killer cell and DC+CIK groups ( P > .05). The highest amount of CD3+ T lymphocyte and Th was recorded after at least 4 cycles of immunotherapy. And CD8+ T/CD4+ T also began to decrease after 4 cycles of immunotherapy. Difference value of T lymphocyte and Tc of patients with surgery is higher than that of patients without surgery. CONCLUSION: Cytokine-induced killer cell-based immunotherapy is capable of increasing T-lymphocyte subsets, recovering cellular immunity without severe side effects, and is suitable for different kinds of solid cancer. Clinical efficiency of cytokine-induced killer cell-based immunotherapy is influenced by many factors such as surgery, stage.
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Células Matadoras Induzidas por Citocinas/imunologia , Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Adulto , Idoso , Antígenos de Neoplasias/imunologia , Células Matadoras Induzidas por Citocinas/patologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Humanos , Imunofenotipagem , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
AIM: To investigate the expression of cyclophilin A (CypA) in human hepatocellular carcinoma (HCC) and explore the effects of CypA on the cell cycle in HCC. MATERIALS AND METHODS: CypA expression was assessed by immunohistochemistry in 48 cases of HCC tissues and paired adjacent tissues. CypA plasmid was transfected into HCC cells and the cell cycle was analyzed. RESULTS: Positivity for CypA was higher in HCC tissues than in adjacent tissues (79.1% vs. 12.5%, p<0.05). Positivity for CypA was significantly higher in stage III and IV HCC than in stage I and II (p<0.05). Elevated CypA induced an increase of the percentage of S-phase cells (from 34.79% to 42.14%) and a decrease of G0-G1 phase cells (from 58.10% to 50.64%). CONCLUSION: CypA is overexpressed in HCC and is associated with TNM stage. CypA also appears to promote the transition of the cell cycle from G1 to S phase.
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Carcinoma Hepatocelular/patologia , Ciclofilina A/metabolismo , Neoplasias Hepáticas/patologia , Regulação para Cima , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Estadiamento de NeoplasiasRESUMO
BACKGROUND/AIM: Biomarkers are essential in early diagnosis and understanding of the molecular mechanism of human cancer. The expression of cyclophilin J, a novel member of the cyclophilin family, was investigated in primary gastric adenocarcinoma. MATERIALS AND METHODS: Western blot analysis was carried out on 36 paired tumor and normal tissue samples; immunohistochemical analysis was carried out on 120 gastric carcinoma tissues and normal adjacent tissue. RESULTS: Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues compared to adjacent normal tissues. Immunohistochemical analysis revealed that cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric carcinoma tissues and adjacent tissues, respectively (p<0.05). Expression of cyclophilin J was associated with the degree of differentiation, but not with lymph node metastasis, gender or depth of tumor infiltration. The overall survival of patients showed no association with the overexpression of cyclophilin J protein. CONCLUSION: Cyclophilin J expression was up-regulated in gastric carcinoma compared to normal gastric tissues. However, in order to confirm its association with the survival of patients with gastric cancer, more cases need to be studied.
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Adenocarcinoma/metabolismo , Ciclofilinas/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Tumorais , Western Blotting , Ciclofilinas/genética , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND/AIM: Bevacizumab combined with standard chemotherapeutics has become a choice of treatment for several kinds of cancers. Hypertension, third-degree albuminuria, thrombosis and cardiotoxicity are the reported side-effects of bevacizumab. Among them, cardiotoxicity is a most severe, but rare outcome. We report a case of a 62-year-old female with colorectal carcinoma who was given bevacizumab-containing chemotherapy for more than 20 months and achieved a stable disease during the entire course of treatment. Thereafter, she developed cardiotoxicity including grade 3 hypertension, tricuspid regurgitation, pulmonary hypertension, left ventricular diastolic dysfunction and pericardial effusion, and was discontinued from the regimen with bevacizumab. CONCLUSION: Although clinically-effective, the severe cardiotoxicity of bevacizumab developed after over 20 courses of treatment prompted us to look for optimal chemotherapy prescription in order to achieve a better clinical outcome.
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Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/complicações , Cardiopatias/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Cardiotoxicidade , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Feminino , Cardiopatias/diagnóstico , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND/AIM: To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. PATIENTS AND METHODS: Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. RESULTS: The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. CONCLUSION: The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects.
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Antineoplásicos/administração & dosagem , Ascite/terapia , Cisplatino/administração & dosagem , Imunoterapia Adotiva , Linfócitos do Interstício Tumoral/transplante , Derrame Pleural Maligno/terapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Ascite/diagnóstico , Ascite/mortalidade , Biomarcadores Tumorais , Cisplatino/efeitos adversos , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Infusões Parenterais , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/mortalidade , Qualidade de Vida , Análise de Sobrevida , Resultado do TratamentoRESUMO
CASE REPORT: This case study reports on a patient who relapsed with thymoma (mixed type) nine years after tumor resection. After four courses of rescue chemotherapy (docetaxel and cisplatinum), the patient was further diagnosed with pure red cell aplasia. It was noticed that cyclosporin A (CsA), which was administered to treat aplasia, could reverse chemoresistance. Its mechanism is not completely clear, but the hypothesis of CsA inhibiting P-glycoprotein mediated drug efflux is the most acceptable.
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Ciclosporina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imunossupressores/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Aplasia Pura de Série Vermelha/etiologia , Timoma/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclosporina/farmacologia , Evolução Fatal , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Aplasia Pura de Série Vermelha/diagnóstico , Timoma/diagnóstico , Timoma/tratamento farmacológico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To observe the effects of Herba Epimedii and Radix Astragali, the two Chinese herbs for replenishing Shen and strengthening qi, on tumor necrosis factor-alpha (TNF-alpha, one of the pro-inflammatory factors) and nuclear factor-kappa B (NF-kappa B) in asthmatic rats. METHODS: Rats were randomly divided into five groups: the normal saline control group, the asthma model group and the three treated groups treated with high, medium and low dose of the Chinese herbs. Serum TNF-alpha and NF-kappa B activity in pulmonary tissue were detected with enzyme-linked immunosorbent assay and immunohistochemistry respectively. RESULTS: Herba Epimedii and Radix Astragali could effectively reduce the production of TNF-alpha and inhibit NF-kappa B activity, and the efficacies in the three treated group were similar, showing insignificant difference among them. CONCLUSION: Application of Herba Epimedii and Radix Astragali in the attack or remission stage of asthma could restrain the development of inflammation by reducing the production of TNF-alpha and inhibiting NF-kappa B activity.
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Asma/tratamento farmacológico , Astragalus propinquus , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Fator de Necrose Tumoral alfa/sangue , Animais , Asma/induzido quimicamente , Asma/metabolismo , Masculino , NF-kappa B/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos BNRESUMO
OBJECTIVE: To evaluate the effect of Fuzheng Quxie granule (FQG) on immune cells and cytokines of populations susceptible to respiratory viral infection. METHODS: One thousand four hundred and two subjects selected from 25 hospitals in Shanghai between May and June in 2003, were divided into the FQG group treated with FQG and the control group treated with placebo. Serum levels of interleukin 2 (IL-2), interleukin 4 (IL-4), gamma-interferon (gamma-IFN), blood lymphocyte subsets (CD3+ , CD4+, CD8+), B-cell count and natural killer cell (NK) percent ratio were measured in 130 of the FQG group and 120 of the control group before treatment, by the end of the 2nd week and two weeks after treatment. RESULTS: By the end of the 2nd week of treatment, as compared with before treatment, the levels of IL-2, gamma-IFN, and NK percent in the FQG group increased significantly (P < 0.05), while IL-4 and CD3+, CD4+, CD8+ and B-cell count were unchanged. Besides, levels of Th1/Th2 ratio markedly increased at the end of the 2nd week and two weeks after treatment, in comparing with that before treatment and in the control group (P<0.05). CONCLUSION: FQG could improve immune function of population susceptible to respiratory viral infection certain extent.
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Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-2/sangue , Fitoterapia , Infecções Respiratórias/prevenção & controle , Viroses/prevenção & controle , Adulto , Relação CD4-CD8 , Método Duplo-Cego , Feminino , Humanos , Interferon gama , Interleucina-4/sangue , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To characterize the biochemical features of the newest member of cyclophilin family of peptidyl-prolyl cis/trans-isomerases (PPIases), cyclophilin J (CYPJ). MATERIALS AND METHODS: PPIase assays were performed on purified hCYPJ and its mutated variants. The substrate specificity, half-maximal inhibitory concentration (IC50) of cyclosporin A (CsA) inhibition and circular dichroism (CD) spectrum of CYPJ were measured. Mercury pathway profiling luciferase assays were also performed. RESULTS: The catalytic number/Michaelis constant (kcat/KM) value of CYPJ was 9.5×10(4) s(-1)M(-1). CYPJ additionally catalyzed norleucine-proline, isoleucine-proline and glutamine-proline peptides compared to CYPA and Escherichia coli PPIases. CYPJ was inhibited by CsA in a dose-dependent manner with IC50 of 12.1±0.9 µM. The CD spectrum of CYPJ was similar to CYPA. CYPJ significantly up-regulated the transcription of E-box, E2F, retinoblastoma (Rb), p53, activator protein 1 (AP1), NF-κB and phospho-cAMP response element (CRE) cis-response element in 293T cells. CONCLUSION: CYPJ structurally resembles CYPA. It is sensitive to inhibition by CsA and plays a role in regulating cell growth, proliferation, and apoptosis.
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Ciclofilinas/metabolismo , Catálise , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ciclofilinas/antagonistas & inibidores , Ciclofilinas/genética , Ciclosporina/metabolismo , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Fatores de Transcrição E2F/genética , Fatores de Transcrição E2F/metabolismo , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica , Células HEK293 , Humanos , Cinética , Mutação , NF-kappa B/genética , NF-kappa B/metabolismo , Ligação Proteica , Proteínas Recombinantes/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Especificidade por Substrato , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Borrmann type IV gastric cancer is a particular histological type of carcinoma, which has the characteristic of diffused infiltration that invades the entire stomach, resulting in the thickening and stiffness of the stomach wall. Borrmann type IV gastric cancer is known for the difficulty of detecting tumor cells in endoscopic biopsy specimens. This is crucial in obtaining the pathological results to make a therapeutic decision. The case reported in the present study was highly suspected to be Borrmann type IV gastric cancer according to the clinical manifestations and gastrointestinal barium meal examinations, but demonstrated negative results in multiple endoscopic biopsies and positron emission tomography-computed tomography (PET-CT) examination. The patient was discharged as no affirmative diagnosis was specified. Two weeks after discharge, the patient was administered to another hospital under emergency treatment due to frequent urination. Cystoscopy examination revealed marked thickening of the right bladder wall over a large area. Biopsy specimens were sampled. Pathological consultation suggested a gastrointestinal original of the lesion, which was most likely poorly differentiated gastric adenocarcinoma with neuroendocrine metastasis to the bladder.
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Cyclophilin (Cyp) A has been reported to be overexpressed in the majority of cancer cells, including hepatocellular carcinoma (HCC). However, the biological functions of CypA in HCC are far from being understood. To determine the biological functions of CypA in HCC, the present study screened human fetal liver complementary DNA for proteins interacting with CypA using the yeast two-hybrid system. A nuclear protein, serine/arginine-rich (SR)-25, was isolated as a novel CypA-binding protein that is distinct from those previously described in the literature. Binding assays and co-immunoprecipitation confirmed the physical association between CypA and SR-25. The present study demonstrated that CypA may interact with SR-25 through its peptidyl-prolyl isomerase domain. In addition, CypA may induce the expression of SR-25 in Hep3B cells. The messenger RNA levels of CypA and SR-25 in HCC indicated that there was a significant correlation between the expression of CypA and the expression of SR-25 in HCC. It can be speculated that the interaction between CypA and SR-25 proteins may be involved in potential carcinogenic functions of CypA in HCC. Further studies will focus on elucidating in detail the molecular mechanisms of the interaction between CypA and SR-25.
RESUMO
OBJECTIVE: To record the efficacy and toxicity of combining bevacizumab with cisplatin in treating malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. PATIENTS AND METHODS: Forty-three patients were admitted to the Oncology Department of Yantai Yuhuangding Hospital with confirmed malignant effusion since January, 2011. Twenty of them received intrapleural and intraperitoneal perfusion of 200 mg bevacizumab plus 60 mg cisplatin every three weeks, and 23 patients received 60 mg cisplatin alone after draining effusion as much as possible. Reduction of effusion was determined by type-B ultrasonography. RESULTS: The complete remission rate and effective rate of bevacizumab group was superior to that of the cisplatin group. The quality of life recovery rate of bevacizumab group was superior to that of the cisplatin group. The anhelation and abdominal distention of bevacizumab group was significantly improved. There was no significant difference in level III/IV toxicities and adverse effects between two groups. CONCLUSION: Bevacizumab significantly improved the objective response rate and quality of life of patients with malignant pleural effusion and ascites, while not causing notable adverse events.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ascite/tratamento farmacológico , Derrame Pleural Maligno/tratamento farmacológico , Bevacizumab/administração & dosagem , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effect of fuzheng quxie granule (FQG) on immune cells and cytokines in populations with respiratory viral infection. METHODS: Fifty-nine patients were randomly divided into 3 groups, that is, 19 patients treated with conventional western medicine (WM) plus FQG in the treated group, 19 patients treated with conventional western medicine alone in the WM group, and 21 patients treated with FQG alone in the TCM group. The levels of T lymphocyte subsets, interleukine-2,4,6,10 (IL-2, IL-4, IL-6, IL-10), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma) and Th1/Th2 were determined before treatment, and at the end of 1st and 2nd week of treatment respectively. RESULTS: Before treatment, levels of TNF-alpha, IL-2, IL-6, IL-10 and INF-gamma in all patients were significantly higher than normal range (P < 0.05). After being treated for 1 week, the levels of serum TNF-alpha, IL-6, and IL-10 were significantly decreased in all groups (P < 0.05), serum IL-2 and INF-gamma decreased to the normal level in the WM group, but in the treated and the FQG group by the end of the 2nd week, the two indexes still remained at the rather higher level (P < 0.05). The ratio of Th1 and Th2 in the treated group and the FQG group increased significantly by the end of 2nd week, reached the level higher than that in the WM group and that before treatment (P < 0.05). No significant difference in, T lymphocytes subsets (CD3+ , CD4+ , CD8+) and percentage of B and NK cells before and after treatment was found in all the 3 groups. CONCLUSION: FQG can positively regulate the immune function of patients with respiratory tract viral infection in certain degree.