RESUMO
Epstein-Barr virus (EBV) is a tumor virus that is associated with a variety of neoplasms, including EBV-associated gastric carcinoma (EBVaGC). Recently, EBV was reported to generate various circular RNAs (circRNAs). CircRNAs are important regulators of tumorigenesis by modulating the malignant behaviors of tumor cells. However, to date, the functions of ebv-circRNAs in EBVaGC remain poorly understood. In the present study, we observed high ebv-circRPMS1 expression in EBVaGC and showed that ebv-circRPMS1 promoted the proliferation, migration, and invasion and inhibited the apoptosis of EBVaGC cells. In addition, METTL3 was upregulated in GC cells overexpressing ebv-circRPMS1. Mechanistically, ebv-circRPMS1 bound to Sam68 to facilitate its physical interaction with the METTL3 promotor, resulting in the transactivation of METTL3 and cancer progression. In clinical EBVaGC samples, ebv-circRPMS1 was associated with distant metastasis and a poor prognosis. Based on these findings, ebv-circRPMS1 contributed to EBVaGC progression by recruiting Sam68 to the METTL3 promoter to induce METTL3 expression. ebv-circRPMS1, Sam68, and METTL3 might serve as therapeutic targets for EBVaGC.
Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Carcinoma/patologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Humanos , Metiltransferases/genética , RNA Circular , Neoplasias Gástricas/patologiaRESUMO
EBV-encoded circular RNA LMP2A (ebv-circLMP2A) was found to be expressed in EBV-associated gastric carcinoma (EBVaGC) and associated with distant metastasis and poor prognosis. Angiogenesis is a key step in tumor invasion and metastasis and plays a crucial role in tumor progression. However, it is unclear whether and how ebv-circLMP2A is involved in angiogenesis. In this study, we showed that MVD, HIF1α, and VEGFA expression was increased in EBVaGC mouse xenografts with high expression of ebv-circLMP2A. The expression of ebv-circLMP2A was positively correlated with MVD, HIF1α, and VEGFA expression in clinical samples of EBVaGC. Knockdown of ebv-circLMP2A repressed tube formation and migration of HUVECs and decreased VEGFA and HIF1α expression in cancer cells under hypoxia, while ectopic expression of ebv-circLMP2A reversed these effects. Additionally, knockdown of HIF1α blocked the upregulation of ebv-circLMP2A by hypoxia, and ebv-circLMP2A interacted with KHSRP to enhance KHSRP-mediated decay of VHL mRNA, leading to the accumulation of HIF1α under hypoxia. There was a positive feedback loop between HIF1α and ebv-circLMP2A that promotes angiogenesis under hypoxia. ebv-circLMP2A was essential in regulating tumor angiogenesis in EBVaGC and might provide a valuable therapeutic target for EBVaGC.
Assuntos
Hipóxia Celular/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias Gástricas/genética , Transativadores/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Humanos , Camundongos , Neovascularização Patológica , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio VascularRESUMO
A Zr-based metal-organic polyhedron (MOP) was self-assembled in a porous MOF host, DUT-68, successfully to synthesize MOP-1@DUT-68. The MOP guest (MOP-1) has a diameter of about 20â Å, larger than that of the square windows (pore sizes of â¼14â Å) of DUT-68 but smaller than that of the rhombicuboctahedral cage (27.7â Å), which means that the migration and leaching of MOP-1 could be effectively prohibited if MOP-1 is encapsulated in the MOF's cavities. The proton conductivity of MOP-1@DUT-68 is 1.14×10-3 â S cm-1 (at 80 °C under 98 % relative humidity), which is three orders of magnitude higher than that of DUT-68. Compared with MOP-1âDUT-68, which was synthesized by impregnation, MOP-1@DUT-68 is more prone to form faster proton-conduction pathways and thus provides higher proton conductivity.
RESUMO
Lumbar disc herniation is a common disease in the clinical context and does great harm to either the physical or mental health of patients suffering from this disease. Many guidelines and consensus for the diagnosis and treatment of lumbar disc herniation have been published domestically and internationally. According to the expert consensus, clinicians could adopt tailored and personalized diagnosis and treatment management strategies for lumbar disc herniation patients.
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Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.
Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Animais , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Circular , Neoplasias Gástricas/genética , Proteínas com Motivo TripartidoRESUMO
This project is to study chemical compositions from the stems of Herpetospermum pedunculosum. Twenty-two compounds were isolated from the 70% acetone extract of the stems of H. pedunculosum by column chromatography on Sephadex LH-20, semi-preparative HPLC and preparative TLC. Their structures were elucidated by their physicochemical properties and spectroscopic data as N-benzyltyramine(1), α-spinasterol(2),(2S)-1-O-heptatriacontanoyl glycerol(3), 5,7-dihydroxychromanone(4), methyl 2ß,3ß-dihydroxy-D:C-friedoolean-8-en-29-oate(5), p-hydroxy benzyl alcohol(6), p-hydroxybenzoate(7), p-hydroxy cinnamic acid(8), 1H-indol-3-carboxylic acid(9), rhodiocyanoside B(10), rhodiolgin(11), rhodiosin(12), 9,12,13-trihydroxy-10(E)-octadecenoic acid(13), cylo-(Tyr-Leu)(14), matteflavoside A(15), loliolide(16), 1H-indol-3-carboxaldehyde(17),(+)-dehydrovomifoliol(18), 3-hydroxy-5α,6α-epoxy-ß-ionone(19), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy-1-propen-1-yl)-2-methoxyphenoxy]-1-propanone(20), 7-en-nonadecanoic acid monoglyceride(21), vanillic acid(22). Compound 1 is a new natural product, while compounds 3-15 were isolated from this plant for the first time.
Assuntos
Cucurbitaceae , Cromatografia Líquida de Alta PressãoRESUMO
Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. The noninferiority margin was defined as -0.15. Other outcomes included daily visual analogue scale score, breakthrough pain (BTP) incidence, intrathecal dose change, and patient-controlled analgesia bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased visual analogue scale scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM -3.33% vs ITMO 35.4%, P < 0.01, t test) from the third week. The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM -19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.
Assuntos
Dor do Câncer , Neoplasias , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , China , Método Duplo-Cego , Humanos , Hidromorfona/uso terapêutico , Injeções Espinhais , Morfina/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Método Simples-CegoRESUMO
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously inflammatory infiltration compared with EBV-negative gastric carcinoma. To date, the local immune status in EBVaGC and its relationship with patient prognosis and apoptosis of tumor cells are largely unknown. In this study, we evaluated the density of different types of tumor-infiltrating lymphocytes (TILs) in 53 EBVaGCs and 67 EBV-negative gastric carcinomas and analyzed its relationship with patient outcomes and apoptosis of tumor cells in EBVaGC. The average number of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, CD56+ natural killer cells, Fascin+ dendritic cells (DCs), and FoxP3+ Tregs and the average proportions of Ki-67, interleukin 1ß, granzyme B, interferon γ, and interleukin 10 in TILs were higher in EBVaGC, and CD8+ T cells were the predominant constituent cells of TILs in EBVaGC. Patients with higher numbers of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs survived longer in EBVaGC, and CD8+ T cells and Fascin+ DCs were independent prognostic factors for patient survival. Besides, CD8+ T cells were positively correlated with apoptotic index of tumor cells. However, the apoptosis of tumor cells was lower, and the expression of survivin and NF-κBp65 in tumor cells was up-regulated in EBVaGC. These findings suggested that CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs predict a better prognosis in EBVaGC; CD8+ T cells might through a nonapoptotic pathway eliminate tumor cells, thereby improving the patient prognosis.
Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas/imunologia , Apoptose , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4 , Humanos , Linfócitos do Interstício Tumoral/patologia , Linfócitos do Interstício Tumoral/virologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologia , Taxa de SobrevidaRESUMO
BACKGROUD: Transarterial chemoembolization (TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanil-based patient controlled analgesia (PCA) could improve the pain management in patients receiving TACE for inoperable HCC. METHODS: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients' age, gender and pain scores, and divided the patients into the multimodal group (nâ¯=â¯42) and control group (nâ¯=â¯42). Patients in the multimodal group received 40â¯mg of parecoxib, 30â¯min before TACE, followed by 48â¯h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5â¯mg of dezocine during operation, and 100â¯mg of tramadol or equivalent intravenous opioid according to patient's complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient's satisfaction were all taken into consideration when evaluated. RESULTS: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12â¯h (all Pâ¯<â¯0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group (31.0% vs. 59.5%). Patient's satisfaction in the multimodal group was also significantly higher than that in the control group (95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. CONCLUSION: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.
Assuntos
Analgesia Controlada pelo Paciente , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Dor Pós-Operatória/terapia , Adulto , Idoso , Quimioembolização Terapêutica/efeitos adversos , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Náusea e Vômito Pós-Operatórios/prevenção & controle , Sufentanil/administração & dosagem , Sufentanil/efeitos adversosRESUMO
About 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV), which are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are usually accompanied by massive lymphocytes infiltration, among which CD8+ T cells are predominant. To date, the apoptosis of the infiltrating CD8+ T cells in EBVaGC has not been investigated. In the present study, we assessed the immunophenotype and apoptosis of tumour infiltrating lymphocytes (TILs) in both EBVaGC and EBV-negative gastric carcinoma (EBVnGC). We found that CD8+CCR7+ T lymphocytes were increased in EBVaGC compared to EBVnGC [60.53 ± 28.41/high power fields (HPF) vs 19.63 ± 15.97/HPF; p < 0.001]. Moreover, the apoptosis index of TILs was lower in EBVaGC than that in EBVnGC (1.34 ± 0.90 vs 5.94 ± 3.77; p < 0.001). Given that the CCL21-CCR7 axis is reported to be potentially involved in apoptosis, we examined the expression of CCL21 in both EBVaGC and EBVnGC. We found that CCL21 expression was higher in EBVaGC than in EBVnGC (p < 0.001). We also showed that the expression of CCL21 by EBVaGC cells protected CD8+CCR7+ T lymphocytes from apoptosis. Furthermore, the up-regulation of Bcl-2 contributed to the inhibition of apoptosis in CD8+CCR7+ T cells. Collectively, these findings suggest that expression of CCL21 by EBVaGC cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway. To our best knowledge, this is the first study to investigate the apoptosis of CD8+ T cells in EBVaGC.
Assuntos
Adenocarcinoma , Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL21/biossíntese , Infecções por Vírus Epstein-Barr/complicações , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Gástricas , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Apoptose/imunologia , Linhagem Celular Tumoral , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/virologiaRESUMO
BACKGROUND: Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. METHODS: 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. RESULTS: 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. CONCLUSION: Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. TRIAL REGISTRATION: The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014.
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Analgesia/métodos , Anestésicos Locais/uso terapêutico , Fígado/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Ropivacaina/uso terapêutico , Músculos Abdominais/diagnóstico por imagem , Músculos Abdominais/efeitos dos fármacos , Adulto , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ropivacaina/administração & dosagem , Solução Salina/administração & dosagem , Método Simples-Cego , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5â×â1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.
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Tumor Carcinoide/secundário , Neoplasias Laríngeas/patologia , Laringe/patologia , Neoplasias Cutâneas/secundário , Pele/patologia , Tumor Carcinoide/etiologia , Tumor Carcinoide/terapia , Feminino , Humanos , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/terapiaRESUMO
Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV) and are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are known to be accompanied by massive CD8(+) cytotoxic T cell (CTL) infiltration; however, adoptive cellular immunotherapy based on EBV-specific CD8(+) CTLs has been explored with limited success. Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, we assessed the distribution of Tregs in 45 cases of EBVaGC and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. We showed that Tregs were significantly increased in EBVaGC compared to EBVnGC (15.92 ± 11.45/HPF vs. 8.45 ± 6.16/HPF, p = 0.001). In addition, we explored the accumulation mechanisms of Tregs in EBVaGC by using EBV (+) gastric carcinoma cell lines SNU719 and GT39 as ex vivo models. When peripheral blood mononuclear cells (PBMCs) were co-cultured with EBV (+) gastric carcinoma cell lines, the Treg frequency increased, and they underwent phenotypic and functional changes. The enhanced recruitment by CCL22 produced by EBVaGC cells, the decreased emigration due to CCR7 downregulation on the Treg surface, the higher proliferation rate, and the lower apoptosis rate of Tregs at tumour sites may promote the accumulation of Tregs in EBVaGC.
Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Neoplasias Gástricas/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Apoptose/imunologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Quimiocina CCL22/imunologia , Quimiocina CCL22/metabolismo , Técnicas de Cocultura , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Feminino , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Herpesvirus Humano 4/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imuno-Histoquímica , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores CCR7/imunologia , Receptores CCR7/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/virologia , Linfócitos T Reguladores/metabolismoRESUMO
OBJECTIVE: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 µmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.
Assuntos
Apoptose/fisiologia , Artrite Reumatoide/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Adulto , Western Blotting , Estudos de Casos e Controles , Sobrevivência Celular/fisiologia , Dactinomicina/farmacologia , Feminino , Citometria de Fluxo , Proteínas Hedgehog/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologia , Receptor Smoothened , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Alcaloides de Veratrum/farmacologiaRESUMO
Expressions of OPN and αvß3 are associated with a poor prognosis in many malignancies. However, their relationship in hepatocellular carcinoma remains unclear. We systematically collected hepatocellular carcinoma tissue samples from 305 patients over 3 years, and analyzed the status of OPN and αvß3 in hepatocellular carcinoma and correlate expression with patient disease status and survival outcome. Our study results indicated that OPN and αvß3 are expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent non-tumorous tissue (69.5% vs 18.4%, p<0.01 and 77.4% vs 21.6%, p<0.01, respectively). Both OPN and αvß3 expression levels are associated with poor prognostic factors, including tumor size, capsular invasion, tumor thrombus of the portal vein, metastasis of the lymph node and clinical staging. Patients expressing OPN and αvß3 had significantly shorter survival compared with patients negative for protein expression (p<0.01). Multivariate analysis also showed that both OPN and αvß3 expression are independent prognostic factors for poorer survival in hepatocellular carcinoma. By this study, we conclude that OPN and αvß3 are negative prognostic predictors in patients with hepatocellular carcinoma. The expressions of both OPN and αvß3 are associated with worse survival outcome.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Integrina alfaVbeta3/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Osteopontina/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVES: Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. METHODS: Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. RESULTS: Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p < 0.0001). CONCLUSIONS: Our study revealed increased severity of inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms.
Assuntos
Cistite Intersticial/metabolismo , Fator de Crescimento Neural/metabolismo , Dor/metabolismo , Canais de Cátion TRPV/metabolismo , Doenças da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation.
Assuntos
Lobectomia Temporal Anterior/métodos , Hidratação/métodos , Ventilação Monopulmonar/métodos , Pneumonectomia/métodos , Volume Sistólico/fisiologia , Toracoscopia/métodos , Idoso , Pressão Arterial/fisiologia , Gasometria , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Projetos Piloto , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation. .