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The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.
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Transtornos de Estresse Pós-Traumáticos , Camundongos , Masculino , Animais , Hipocampo , Aprendizagem Espacial , Neurônios GABAérgicosRESUMO
The purpose of this study was to investigate the effects of acute fear stress on the spatial memory and neuronal plasticity of medial prefrontal cortex (mPFC) neurons in mice, and to elucidate the mechanisms underlying mPFC plasticity and post-stress memory regulation. Male C57BL/6 mice (6 weeks old) were randomly divided into control group and stress group. Foot shock stress was applied to establish an acute fear stress model. Changes in spatial memory were examined by the Morris water maze test, and the dynamic changes in the spike encoding of pyramidal neurons and GABAergic neurons in the prelimbic cortex (PrL) and infralimbic cortex (IL) of mPFC were detected by whole-cell recording. The results showed that acute fear stress significantly enhanced the percentage of freezing and the number of freezing, reduced the average speed, decreased the escape latency during acquisition phase, extended the probing time in the first quadrant and shortened the probing time in the third quadrant during probe trial, increased inter-spike interval, energy barrier and absolute refractory period of GABAergic neurons in the PrL and pyramidal neurons in the IL, while decreased inter-spike interval, energy barrier and absolute refractory period of pyramidal neurons in the PrL and GABAergic neurons in the IL. These results suggest that acute fear stress can enhance the spatial memory of mice, elevate the excitability and function of the PrL, while deteriorate the excitability and function of the IL, and the underlying mechanism may involve the role of mPFC microcircuitry plasticity in spatial memory after stress.
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Plasticidade Neuronal , Memória Espacial , Animais , Masculino , Camundongos , Medo , Camundongos Endogâmicos C57BL , Córtex Pré-FrontalRESUMO
Previously, we showed that treatment with celecoxib obviously inhibited proliferation of nasopharyngeal carcinoma (NPC) cell lines in a dose-dependent manner. However, the underlying molecular mechanisms of its anticancer effect on NPC have not been fully clarified. The present in vitro study was performed to investigate the mechanisms involved in the anticancer effect of celecoxib in NPC. NPC cell line HONE1 was treated with celecoxib at varying concentrations. The antiproliferation effect of celecoxib on the HONE1 cell line was assessed with methyl thiazolyl tetrazolium (MTT) assay. Western blot analysis of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), Survivin, Mcl-1, Bcl-2 and Cyclin D1 was carried out at various concentration of celecoxib for 48 h in HONE1 cell line. Western blot analysis of Protein Kinase B (AKT), phosphorylated AKT (pAKT) was performed at increasing doses of celecoxib for 48 h in HNE1, CNE1-LMP1 and HONE1 cells. The results showed that celecoxib inhibited proliferation of HONE1 cell line in a dose-dependent manner. Celecoxib inhibited the activation of STAT3 phosphorylation in HONE1 cells and the downstream genes of STAT3 (Survivin, Mcl-1, Bcl-2 and Cyclin D1) were downregulated after treatment with celecoxib. Furthermore, celecoxib could inhibit AKT phosphorylation in HNE1, CNE1-LMP1 and HONE1 cell lines. These data suggested that celecoxib was a promising agent for the chemoprevention and treatment of NPC.
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Antineoplásicos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/farmacologia , Western Blotting , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Corantes , Humanos , Fosforilação , Sais de Tetrazólio , TiazóisRESUMO
Celecoxib is a selective inhibitor of COX-2, whose connection with the development and progression of human tumors has been extensively studied. So far, however, its anti-metastatic effect is poorly understood in nasopharyngeal carcinoma. The current study aimed to observe the effect of celecoxib on invasion and migration of nasopharyngeal carcinoma cell lines and investigate the potential mechanism in vitro. Human nasopharyngeal carcinoma cell lines HNE1, HONE1, SUNE1-5-8F were exposed to different concentrations of celecoxib. MTT assay was used to study its anti-proliferation effect, transwell assay wound healing repair assay were performed to investigate the invasiveness and migration capability after treatment with celecoxib. The activity of MMP-2 and MMP-9 was measured by gelatin zymography. MTT assay showed that celecoxib inhibited HNE1, HONE1, and SUNE1-5-8F cells growth. Wound healing repair assay and transwell assay showed that cell metastatic ability was suppressed after treatment with celecoxib. Celecoxib had a significant inhibitory effect on the activity of MMP-2/9 in a dose-dependent manner in HNE1, HONE1 and SUNE1-5-8F cell lines. These data demonstrated that celecoxib-induced suppression of MMP-2 and MMP-9 activity might be involved in the inhibition of nasopharyngeal carcinoma cell lines invasion and migration.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Inibidores de Metaloproteinases de Matriz , Neoplasias Nasofaríngeas/tratamento farmacológico , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Carcinoma , Celecoxib , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Corantes , Relação Dose-Resposta a Droga , Humanos , Indicadores e Reagentes , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Sais de Tetrazólio , Tiazóis , Cicatrização/efeitos dos fármacosRESUMO
Ganpu vine tea is a new type of health care citrus fruit tea made from citrus shell, Pu-er tea, and vine tea baked as raw materials. In this study, the in vitro uric acid synthase inhibition system and hyperuric acid cell model were constructed to appraise the uric acid lowering efficacy of Ganpu vine tea, traditional Ganpu tea, and vine tea. Results showed that in the uric acid synthase inhibition system, the aqueous extract can inhibite the puric metabolically related enzymes, such as adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XOD). The ability of the aqueous extract to inhibit the above enzyme was as follows: vine tea > Ganpu vine tea > Ganpu tea; all teas had a strong effect on XOD inhibition. The hyperuric acid cell model test showed that the aqueous extract inhibited uric acid production through accumulating inosine and hypoxanthine and hindering xanthine synthesis. The uric acid reductive ability was as follows: Vine tea > Ganpu vine tea > Ganpu tea. The inhibition of enzymes related to uric acid synthesis and the inhibition of uric acid production were significantly enhanced through adding vine tea to Ganpu tea. It also shows that flavonoids are the main factor driving this ability because they are the main active ingredients in these botanical drinks.
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Clinical definition and appropriate management of anaphylaxis is a clinical challenge because there is large variability in presenting clinical signs and symptoms. Monitoring of the metabolic status of anaphylaxis may be helpful in understanding its pathophysiological processes and diagnosis. The purpose of this study was to conduct GC-MS serum metabolic profiling of anaphylaxis animal models and search for potential biomarkers of anaphylaxis. Thirty-six guinea pigs were randomly divided into an ovalbumin group (n = 12), a cattle albumin group (n = 12), and a control group (n = 12). The IgE level in the serum of the guinea pigs was evaluated by use of ELISA kits and the major metabolic changes in serum were detected by gas chromatography-mass spectrometry. Typical clinical symptoms appeared after the animals had been challenged with ovalbumin or cattle albumin. The IgE levels in serum of both model groups were significantly higher than those of the control group. Clustering trend of the three groups based on variables was observed and nine out of 858 metabolomic features were found to be significantly different between control group and model groups. Among the nine features, six features were tentatively identified as metabolites related to energy metabolism and signal transduction in anaphylaxis. In conclusion, GC-MS-based metabolic profiling analysis might be an effective auxiliary tool for investigation of anaphylaxis.
Assuntos
Anafilaxia/sangue , Imunoglobulina E/sangue , Metabolômica , Alérgenos/administração & dosagem , Alérgenos/efeitos adversos , Alérgenos/imunologia , Anafilaxia/induzido quimicamente , Anafilaxia/imunologia , Animais , Biomarcadores/sangue , Bovinos , Metabolismo Energético/imunologia , Ensaio de Imunoadsorção Enzimática , Cromatografia Gasosa-Espectrometria de Massas , Cobaias , Imunoglobulina E/imunologia , Metaboloma , Modelos Animais , Ovalbumina/administração & dosagem , Ovalbumina/efeitos adversos , Ovalbumina/imunologia , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/efeitos adversos , Soroalbumina Bovina/imunologia , Transdução de Sinais/imunologiaRESUMO
AIM: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC). METHODS: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1. RESULTS: Celecoxib (10-75 µmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 µmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 µmol/L). CONCLUSION: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Nasofaríngeas/metabolismo , Pirazóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Sulfonamidas/farmacologia , Western Blotting , Carcinoma , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Interleucina-6/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Fosforilação , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated. OBJECTIVE: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH. DESIGN: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting. RESULTS: The ∆7-phytosterols in TPS reached up to 87.64%. Among them, 24ß-ethylcholesta-7,22,25-trienol, 24ß-ethylcholesta-7,25(27)-dien-3-ol, and ∆7-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-ß1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation. CONCLUSION: TPS from hull-less pumpkin seed oil, with ∆7-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.
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OBJECTIVE: To observe the effect of amylin on the islet beta-cells voltage-gated L-calcium channels in rats. METHOD: Patch clamp technique was employed in the observation of the features and changes of electric current of islet beta-cells voltage-gated L-calcium channels before and after using amylin. RESULTS: In the glucose environment of 5.5 mmol/L, the electric current of rat islet beta-cells voltage-gated L-calcium channels was activated at -40 mV and reached the peak at about +20 mV, with a peak value of about -120 pA and the insulin secretion level was (0.76 +/- 0.12) microg/L. Under the stimulation of glucose of 16.7 mmol/L, the peak current voltage moved to the left and increased up to - 140 pA and the level of insulin secretion measured (1.78 +/- 0.13) microg/L. Hatch islet beta-cells in amylin at the concentrations of 0.5, 1.0, 5.0 and 10.0 micromol/L, respectively. It was observed that in the 0.5 micromol/L and 1.0 micromol/L groups, there was no remarkable change in the peak potential activation voltage, current, and insulin secretion volume in comparison with the control group. However, in the environment of 5.5 mmol/L glucose, the increase of activation voltage of the 5.0 and 10.0 micromol/L groups was - 30 mV, with the peak current reduced to approximately -80 pA and -60 pA and the insulin secretion decreased to (0.49 +/- 0.11) microg/L and (0.36 +/- 0.12) microg/L respectively. Under the concentration of 16.7 mmol/L glucose, the activation voltage increased from -40 mV up to -30 mV and the peak current reduced to -80 pA and -40 pA. In the meantime, the insulin secretion decreased respectively to (1.20 +/- 0.13) microg/L and (0.89 +/- 0.14) microg/L, which is of significance. CONCLUSION: The secretion of insulin is synchronized with the opening of the islet beta-cells voltage-gated L-calcium channels at the stimulation of glucose. The amylin inhibition of the insulin secretion is also synchronized with the opening of islet beta-cells voltage-gated L-calcium channels and it's in a positive concentration-dependent manner.
Assuntos
Amiloide/farmacologia , Canais de Cálcio Tipo L/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Animais , Células Cultivadas , Insulina/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
Accumulating evidence have suggested that long noncoding RNAs (lncRNAs) are known to regulate diverse tumorigenic processes. Recently, a novel lncRNA LINC01939 was underexpressed and emerged as a tumor suppressive lncRNA in gastric cancer (GC). In this study, we aimed to investigate the biological function and molecular mechanism of LINC01939 in GC. We found that LINC01939 expression was significantly downregulated in GC tissues and cell lines. Low expression of LINC01939 was correlated with tumor metastasis and shorter survival in GC patients. Functionally, LINC01939 overexpression remarkably inhibited the invasion and migration of GC cells in vitro and in vivo. Mechanistically, LINC01939 regulated the expression of early growth response 2 (EGR2) protein by competitively binding to miR-17-5p. Upregulation of miR-17-5p reversed GC metastasis and EMT process caused by LINC01939 by rescue analysis. Taken together, these results suggested that LINC01939 repressed GC invasion and migration by functioning as a ceRNA for miR-17-5p to regulate EGR2 expression. Our findings provided a novel prognostic marker and therapeutic target for GC patients.
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Proteína 2 de Resposta de Crescimento Precoce/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Células HEK293 , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Prognóstico , Intervalo Livre de Progressão , Neoplasias Gástricas/patologia , TransfecçãoRESUMO
As highly tissue-specific genes, it is increasingly recognized that long non-coding RNAs (lncRNAs) are considered as promising prognostic biomarkers for multiple human cancers. However, lack of tissue-specific lncRNAs in gastric cancer (GC) still exist. In this study, we identified a novel lncRNA LINC01939 which showed the largest fold change in GC than other human cancers from lnCAR database by bioinformatic analysis. Reverse transcription quantitative polymerase chain reaction (qPCR) assay confirmed that LINC01939 was significantly downregulated in GC tissues compared with matched normal tissues. Low expression of LINC01939 was positively associated with advanced TNM stage and lymphatic metastasis. Patients with low LINC01939 expression have remarkably shorter overall survival (OS) and progression-free survival (PFS) than those with high LINC01939 expression. Univariate and multivariate analysis showed that LINC01939 is an independent protective predictor of OS and PFS in GC patients. Therefore, our data suggest that the newly identified lncRNA LINC01939 might act as a potential prognostic biomarker for GC.
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RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidadeRESUMO
Soil bacteria play a key role in the ecological and evolutionary responses of agricultural ecosystems. Domestic herbivore grazing is known to influence soil bacterial community. However, the effects of grazing and its major driving factors on soil bacterial community remain unknown for different plant community compositions under increasing grazing intensity. Thus, to investigate soil bacterial community diversity under five plant community compositions (Grass; Leymus chinensis; Forb; L. chinensis & Forb; and Legume), we performed a four-year field experiment with different grazing intensity treatments (no grazing; light grazing, 4 sheep·ha-1; and heavy grazing, 6 sheep·ha-1) in a grassland in China. Total DNA was obtained from soil samples collected from the plots in August, and polymerase chain reaction (PCR) analysis and denaturing gradient gel electrophoresis (DGGE) fingerprinting were used to investigate soil bacterial community. The results showed that light grazing significantly increased indices of soil bacterial community diversity for the Forb and Legume groups but not the Grass and L. chinensis groups. Heavy grazing significantly reduced these soil bacterial diversity indices, except for the Pielou evenness index in the Legume group. Further analyses revealed that the soil N/P ratio, electrical conductivity (EC), total nitrogen (TN) and pH were the major environmental factors affecting the soil bacterial community. Our study suggests that the soil bacterial community diversity was influenced by grazing intensity and plant community composition in a meadow steppe. The present study provides a baseline assessment of the soil bacterial community diversity in a temperate meadow steppe.
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Biodiversidade , Ecossistema , Poaceae/microbiologia , Microbiologia do Solo , Animais , Eletroforese em Gel de Gradiente Desnaturante , Reação em Cadeia da Polimerase , OvinosRESUMO
OBJECTIVES: Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated in aortic aneurysm risk, but individual published studies show inconclusive results. The aim of this study was to explore a more precise estimation of its relation with aortic aneurysm using meta-analysis. METHODS: Electronic searches of PubMed and EMBASE databases were conducted for all publications through February 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the strength of this association in the random-effects model or fixed-effects model. RESULTS: Fourteen case-control studies, including a total of 3938 cases and 5748 controls, were included. This meta-analysis showed a significant association between ACE I/D polymorphism and aortic aneurysm risk (OR = 1.53, 95% CI 1.26-1.87, P <0.01). In the subgroup analysis by ethnicity, a statistically significant association was found in Caucasians (OR = 1.46, 95% CI 1.20-1.77, P <0.01), but not in Asians. In the subgroup analysis by type of aortic aneurysm, this polymorphism was significantly associated with abdominal aortic aneurysm risk (OR = 1.38, 95% CI 1.10-1.74, P <0.01), thoracic aortic aneurysm risk (OR = 1.59, 95% CI 1.11-2.29, P = 0.01) and aortic dissection risk (OR = 2.43, 95% CI 1.07-5.52, P = 0.03). Stratification by hypertension status showed that hypertensive patients with this polymorphism were associated with increased aortic aneurysm risk (OR = 1.47, 95% CI 1.03-2.09, P = 0.03), whereas normotensive individuals with this polymorphism did not have an increased aortic aneurysm risk. CONCLUSIONS: This meta-analysis suggested that ACE I/D polymorphism was associated with aortic aneurysm risk.
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Aneurisma Aórtico/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Aneurisma Aórtico/enzimologia , Humanos , Peptidil Dipeptidase A/metabolismo , Fatores de RiscoRESUMO
OBJECTIVES: The primarily aim of this phase II study is to evaluate the response rate (RR) and disease control rate (DCR). The secondary aim of this study is to assess the progression-free survival and overall survival of recurrent or metastatic nasopharyngeal carcinoma (NPC) patients treated with lobaplatin in combination with docetaxel. MATERIALS AND METHODS: Patients with recurrent and metastatic NPC received docetaxel (75 mg/m(2) on day 1) and lobaplatin (30 mg/m(2) on day 2) every 3 weeks for two to six courses. RESULTS: From April 2011 to July 2013, 39 patients were enrolled. In total, 3 patients (7.7%) had complete response, 21 (53.8%) had partial response, 9 (23.1%) had stable disease and 4 (10.3%) had progressive disease. The overall RR was 61.5% (95% CI, 46.2-76.8%), and the DCR was 84.6% (95% CI, 73.3-95.9%). The median time to progression was 10 months (95% CI, 7.3-12.8 months) after the median follow-up duration of 10.3 months (1.5-28.9 months). The most common grade 3/4 toxicities included leucopaenia and neutropaenia (17.9%), anaemia (5.1%) and increased aminotransferase level (2.6%). Other toxicities were grade 1/2 and minimal. CONCLUSION: Lobaplatin in combination with docetaxel demonstrated clinical activity and an acceptable toxicity profile in recurrent and metastatic NPC patients. Lobaplatin may be effective for recurrent and metastatic NPC patients who previously received cisplatin-based chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Metástase Neoplásica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclobutanos/administração & dosagem , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Compostos Organoplatínicos/administração & dosagem , Recidiva , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
AIM: To investigate the correlations between lipid metabolism disorder and the occurrence and development of colorectal cancer by monitoring the alterations in lipid levels in cancerous tissue and serum in patients with colorectal cancer. METHODS: The levels of total and free cholesterol (TCH and FCH), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), apolipoprotein A1 (ApoA-1) and ApoB in serum of 206 patients with colorectal cancer, 70 patients with benign colorectal disease and 300 healthy participants, and in the cancerous tissue and paracancerous tissue of 152 patients with colorectal cancer were measured with an Olympus 600 auto-biochemical analyzer. The obtained data were statistically analyzed. RESULTS: Serum FCH level was significantly higher (1.9 ± 0.4 mmol/L vs 1.3 ± 0.3 mmol/L, 1.9 ± 0.4 mmol/L vs 1.2 ± 0.4 mmol/L, P < 0.05), whereas serum levels of TCH, LDL-C, ApoA-I and ApoB were significantly lower in patients with colorectal cancer than in patients with benign colorectal disease and healthy controls. The levels of FCH and TG in cancerous tissue were significantly lower (14.5 ± 9.6 µmol/g vs 19.3 ± 13.9 µmol/g, P < 0.05; 16.3 ± 19.8 µmol/g vs 44.1 ± 38.1 µmol/g, P < 0.05), whereas HDL-C level was significantly higher (7.9 ± 4.5 µmol/g vs 5.7 ± 3.9 µmol/g, P < 0.01) in cancerous tissue than in paracancerous tissue. The levels of TCH and TG in serum and the levels of TCH and HDL-C in cancerous tissue in patients with colorectal cancer were significantly correlated with TNM stage. The levels of TCH and LDL-C in serum were significantly lower, whereas HDL-C level in cancerous tissue was significantly higher in patients with lymph node metastasis than in patients without lymph node metastasis. The levels of TCH, FCH, TG, HDL-C and LDL-C in cancerous tissue were not significantly different from those in paracancerous tissue. The serum levels of FCH and TG were significantly higher, whereas serum HDL-C levels were significantly lower in patients with rectum cancer than in patients with colon cancer. CONCLUSION: The disordered and abnormally altered levels of lipids in cancerous tissue and serum of patients with colorectal cancer may be correlated with the occurrence and development of colorectal cancer.
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Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/química , Dislipidemias/sangue , Lipídeos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Dislipidemias/diagnóstico , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos TestesRESUMO
AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay (ELISA). In the meantime, their body mass index (BMI) and waist-to-hip ratio (WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients (P < 0.05 and P < 0.001, respectively). There is no significant difference (P > 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease.
Assuntos
Neoplasias Colorretais/patologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Insulina/metabolismo , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Relação Cintura-Quadril , Adulto JovemRESUMO
Nasopharyngeal carcinoma (NPC) shows the highest invasive and metastatic features among head and neck cancers. Distant metastasis remains the predominant mode of treatment failure in NPC patients. The role of interleukin-6 (IL-6) in NPC progression is not fully understood. In this study, we explored whether IL-6 could promote the migration and invasion activity of NPC cell lines, as well as whether the effect of IL-6 on cell migration and invasion is mediated through regulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Our results revealed that IL-6 and its receptors are broadly expressed in various NPC cell lines including HNE1, HONE1, CNE1, CNE1-LMP1 and 5-8F. Exogenous IL-6 enhanced cell proliferation slightly, but promoted cell migration and invasion significantly in both HNE1 and CNE1-LMP1 cell lines. In addition, an elevation in the expression of MMP-2 and MMP-9 could be induced by IL-6 stimulation. On the contrary, combining treatment with monoclonal anti-human IL-6R antibody (anti-IL-6R mAb) resulted in decreased proliferation, migration and invasion capabilities of NPC cells. Anti-IL-6R mAb also inhibited the expression of MMP-2 and MMP-9 in IL-6-stimulated HNE1 and CNE1-LMP1 cells. In summary, our data suggested that IL-6 mainly promotes the cell migration and invasion of NPC cells. The effect of IL-6 on cell migration and invasion may be mediated through regulation of the expression of MMP-2 and MMP-9. Thus, IL-6 or its related signaling pathways may be a promising target for preventing and inhibiting NPC metastasis.
Assuntos
Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Nasofaríngeas/metabolismo , Invasividade Neoplásica/patologia , Carcinoma , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Transdução de SinaisRESUMO
Curcumin is a natural polyphenol product derived from the rhizome of the Curcuma longa. In vivo and in vitro studies have uncovered many important bioactivities of curcumin, such as antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and anti-microbe properties. Based on these functions, curcumin has been used in clinical trials on various inflammatory diseases and cancers. In the future, it will be necessary to focus attention partly on the clinical application of curcumin in neurodegenerative diseases, cardiovascular diseases and diabetes, because many experiments have clarified the potential value of curcumin in these areas. As a diet-derived agent, curcumin has no severe toxicity except for minor gastrointestinal side effects even up to the dosage of 8 grams for 3 months. However, curcumin has a low systemic bioavailability, so it is imperative to improve the bioavailability of curcumin in its clinical application. Many methods, such as adjuvant drug delivery system and structural modification have been demonstrated to have a potential effect.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Disponibilidade Biológica , Química Farmacêutica , Curcumina/efeitos adversos , Curcumina/análogos & derivados , Curcumina/química , Curcumina/farmacocinética , Portadores de Fármacos , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Angiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avß3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avß3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer. METHODS: USPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avß3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avß3 integrin expression and vessel distribution in A549 tumor xenografts. RESULTS: HUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avß3 integrin expression. CONCLUSIONS: RGD-USPIO could specifically label avß3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.
Assuntos
Dextranos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/uso terapêutico , Neovascularização Patológica/prevenção & controle , Oligopeptídeos/uso terapêutico , Animais , Células Cultivadas , Humanos , Integrina alfaVbeta3/análise , Neoplasias Pulmonares/irrigação sanguínea , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The carboxyl terminus of heat shock cognate 70 interacting protein (CHIP) is an E3 ubiquitin ligase, which can promote ubiquitylation and degradation of many tumor-related proteins. However, the expression of CHIP in human gastric cancer has not been investigated. In this study, the mRNA and protein levels of CHIP expression in 53 cases of gastric cancer and matched normal tissues were determined by quantitative real-time PCR, western blotting and immunohistochemistry. We showed that CHIP was registered from basal to middle portions of normal gastric mucosa. CHIP expression was notably decreased or lost in human gastric cancer samples compared with the matched normal non-cancer samples. The correlations between CHIP downregulation and the clinicopathological characteristics were also evaluated. The expression of CHIP was significantly lower in the gastric cancer samples compared to the matched normal samples at both mRNA and protein levels (P<0.05 and P<0.05, respectively). More importantly, the downregulation of CHIP was correlated with TNM stage (P=0.048) and lymph node metastasis (P=0.010) at the mRNA levels. In addition, the downregulation of CHIP was correlated with lymph node metastasis (P=0.021) and tumor differentiation (P=0.009) at the protein levels. Taken together, at both mRNA and protein levels, the decreased expression of CHIP was correlated with lymph node metastasis. Furthermore, our study suggests that a negative correlation exists between CHIP expression and tumor malignancy in human gastric cancer.