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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(8): 780-786, 2023 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-37574295

RESUMO

Objective: To investigate the risk factors for organoid culture failure in colorectal cancer. Methods: This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples. Results: The median (range) duration of organoid culture was 7 (3-12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant (P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335-0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285-0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154-63.131,P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112-61.882, P=0.039) were identified as independent protective factors. Conclusions: The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.


Assuntos
Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Ascite , Quimiorradioterapia , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Organoides , Prognóstico
3.
Zhonghua Yi Xue Za Zhi ; 100(41): 3230-3234, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33167109

RESUMO

Objective: To evaluate the effect on bleeding volume and postoperative recovery of regional cerebral oxygen saturation (rSO(2)) guides controlled hypotension in elderly patients with hypertension undergoing spinal surgery. Methods: One hundred and twenty elderly patients who underwent spinal surgery in the department of anesthesiology of Qingdao Municipal Hospital and the Affiliated Hospital of Qingdao University from January 2017 to December 2019 were selected and divided into 2 groups according to the random number table method (n=60): rSO(2) guides the controlled hypotension group (group A) and control group (group C). Both groups were performed with endotracheal intubation for general anesthesia, maintain anesthesia with sevoflurane and remifentanil, rSO(2) were monitored throughout the procedure. If necessary, sodium nitroprusside or esmolol were used to control blood pressure. In group A, the goal of controlled hypotension was that rSO(2) decreased ≤ 10% of the basic value or maintained at 64±3 and the moderate operative field bleeding. Group C underwent routine anesthesia management. Intraoperative blood loss and urine output, the incidence of hypothermia after operation, postoperative delirium, chills, nausea and vomiting, the PACU residence time, postoperative drainage volume, eating time, postoperative hospital stay were compared between the two groups. Results: Compared with group C, the blood loss [(589±157) vs (764±213) ml] and urine output [(778±121) vs (1 079±239) ml] of group A were decreased (t=-5.120, -8.712, all P<0.05). The rates of hypothermia after operation (26.7% vs 45.0%), postoperative delirium (18.3% vs 36.7%), chills (10.0% vs 25.0%), nausea and vomiting (21.7% vs 40.0%) of group A were decreased (χ(2)=4.385, 5.057, 4.675, 4.728, all P<0.05) . The PACU residence time [(56±9) vs (63±11) min], postoperative drainage volume [(217±66) vs (289±81) ml], eating time [(17.8±2.8) vs (22.3±4.1) h] and numbers of days in hospital [(7.2±2.7) vs (8.2±2.9) d] were decreased of group A (t=-3.399, -5.334, -7.000, -2.031, all P<0.05). Conclusion: The guidance of controlled hypotension with rSO(2) monitoring can reduce the blood loss and infusion volume during spinal surgery in elderly patients with hypertension, reduce postoperative related complications and enhance recovery after surgery.


Assuntos
Hipertensão , Hipotensão Controlada , Idoso , Humanos , Oxigênio , Período Pós-Operatório , Sevoflurano
4.
Zhonghua Shao Shang Za Zhi ; 33(11): 694-698, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29166712

RESUMO

Objective: To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms. Methods: Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-ß(1) (TGF-ß(1)), and endostatin+ TGF-ß(1) groups according to the random number table, with 3 wells in each group. Cells in blank control group were cultured with DMEM medium for 24 h. Cells in endostatin group were cultured with DMEM medium containing 5 µg/mL endostatin for 24 h. Cells in PDGF-BB group and TGF-ß(1) group were cultured with DMEM medium containing 200 ng/mL PDGF-BB and 10 ng/mL TGF-ß(1) for 24 h, respectively. Cells in endostatin+ PDGF-BB group were pretreated with DMEM medium containing 5 µg/mL endostatin for 48 h and then cultured with DMEM medium containing 200 ng/mL PDGF-BB for 24 h. Cells in endostatin+ TGF-ß(1) group were pretreated with DMEM medium containing 5 µg/mL endostatin for 48 h and then cultured with DMEM medium containing 10 ng/mL TGF-ß(1) for 24 h. The content of type Ⅰ collagen in the cell culture supernatant of three wells in each group was determined by enzyme-linked immunosorbent assay. The protein expression levels of α-smooth muscle actin (α-SMA), PDGF receptor ß (PDGFRß), phosphorylated PDGFRß (p-PDGFRß), and phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) of three wells in each group were detected by Western blotting. Data were processed with one-way analysis of variance and SNK test. Results: (1) Compared with (5.05±0.29) pg/mL in blank control group, content of type Ⅰ collagen in the cell culture supernatant of endostatin group [(4.72±0.37) pg/mL] was close to it (P>0.05), content of type Ⅰ collagen in the cell culture supernatant of PDGF-BB group and TGF-ß(1) group [(8.60±0.57) and (9.20±0.64) pg/mL, respectively] was higher (with P values below 0.05). Content of type Ⅰ collagen in the cell culture supernatant of endostatin+ PDGF-BB group [(5.32±0.17) pg/mL] was lower than that of PDGF-BB group (P<0.05), and content of type Ⅰ collagen in the cell culture supernatant of endostatin+ TGF-ß(1) group [(5.41±0.20) pg/mL] was lower than that of TGF-ß(1) group (P<0.05). (2) Compared with those in blank control group, protein expression levels of α-SMA, PDGFRß, p-PDGFRß, and p-ERK1/2 of cells in endostatin group showed no obvious differences (with P values above 0.05), while those in PDGF-BB and TGF-ß(1) group were significantly higher (with P values below 0.01). Protein expression levels of α-SMA, PDGFRß, p-PDGFRß, and p-ERK1/2 of cells in endostatin+ PDGF-BB group and endostatin+ TGF-ß(1) group were significantly lower than those in PDGF-BB group and TGF-ß(1) group, respectively (with P values below 0.05). Conclusions: Pretreatment of endostatin can inhibit the fibrosis of human skin fibroblast and its transformation into myofibroblast, which may be related to the down-regulation of protein expression of p-PDGFRß, PDGFRß, and p-ERK.


Assuntos
Colágeno Tipo I/metabolismo , Endostatinas/farmacologia , Fibroblastos/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Becaplermina , Células Cultivadas , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Humanos , Fator de Crescimento Derivado de Plaquetas , Proteínas Proto-Oncogênicas c-sis
5.
Sleep Breath ; 21(1): 191-195, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28101753

RESUMO

PURPOSE: Primary insomnia is a persistent and recurrent disorder as well as a risk factor for depression. The aim of this study was to determine whether the zolpidem combined with paroxetine would be effective in the treatment of patients with primary insomnia. METHODS: Ninety patients meeting DSM-IV criteria for primary insomnia were randomly assigned to 8 weeks of treatment with zolpidem combined with paroxetine (the combined treatment group, n = 45) or zolpidem combined with placebo (the control group, n = 45). Patients were assessed with the Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG), and the Treatment Emergent Symptom Scale (TESS). RESULTS: Compared with the control group, the combined treatment group was more significantly improved on wake time after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE), and total PSQI scores, but not the sleep onset latency (SOL). CONCLUSIONS: Eight weeks of the zolpidem combined with paroxetine treatment to patients with primary insomnia is more effective than zolpidem treatment only in sleep maintenance and early morning awakenings.


Assuntos
Paroxetina/efeitos adversos , Paroxetina/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Resultado do Tratamento , Vigília/efeitos dos fármacos , Zolpidem
6.
Clin Exp Dermatol ; 41(8): 858-863, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27759171

RESUMO

BACKGROUND: Zerumbone (ZER) is a phytochemical that appears to regulate cell proliferation and apoptosis. It has been reported to have an anti-tumour effect in various malignant cells; however, the effect and the mechanism of ZER on melanoma cells needs to be clarified. AIM: To explore whether ZER has an effect on human melanoma cells and to identify the mechanisms involved. METHODS: We determined the chemotherapeutic action of ZER on the human malignant melanoma (MM) A375 cell line by CCK-8 immunohistochemistry, Hoechst 33342 staining and flow cytometry analysis. We also investigated the signalling pathways by which ZER induces apoptosis in A375 cells, using western blotting, reverse transcription PCR and caspase-3 activity analysis. RESULTS: ZER induced significant cytotoxic action in A375 cells. Hoechst 33342 staining and flow cytometry apoptosis analysis further demonstrated that ZER induced apoptosis in A375 cells. Treatment with ZER downregulated Bcl-2 gene and protein levels, upregulated Bax and Cytochrome c gene and protein levels, and activated Caspase-3. CONCLUSIONS: ZER might have a chemotherapeutic effect on human melanoma cells through mitochondria-mediated pathways.


Assuntos
Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Melanoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
7.
Sci Rep ; 6: 29471, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27387817

RESUMO

Effect of solid solution treatment (T4) on stress corrosion cracking (SCC) behavior of an as-forged Mg-6.7%Zn-1.3%Y-0.6%Zr (in wt.%) alloy has been investigated using slow strain rate tensile (SSRT) testing in 3.5 wt.% NaCl solution. The results demonstrated that the SCC susceptibility index (ISCC) of as-forged samples was 0.95 and its elongation-to-failure (εf) was only 1.1%. After T4 treatment, the SCC resistance was remarkably improved. The ISCC and εf values of T4 samples were 0.86 and 3.4%, respectively. Fractography and surface observation indicated that the stress corrosion cracking mode for as-forged samples was dominated by transgranular and partially intergranular morphology, whereas the cracking mode for T4 samples was transgranular. In both cases, the main cracking mechanism was associated with hydrogen embrittlement (HE). Through alleviating the corrosion attack of Mg matrix, the influence of HE on the SCC resistance of T4 samples can be greatly suppressed.

8.
Sci Rep ; 6: 23955, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27032532

RESUMO

Through investigating and comparing the fatigue behavior of an as-forged Mg-6.7Zn-1.3Y-0.6Zr (wt.%) alloy before and after solid solution treatment (T4) in laboratory air, the effect of T4 treatment on fatigue crack initiation was disclosed. S-N curves illustrated that the fatigue strength of as-forged samples was 110 MPa, whereas the fatigue strength of T4 samples was only 80 MPa. Observations to fracture surfaces demonstrated that for as-forged samples, fatigue crack initiation sites were covered with a layer of oxide film. However, due to the coarse grain structure and the dissolution of MgZn2 precipitates, the activation and accumulation of {10-12} twins in T4 samples were much easier, resulting in the preferential fatigue crack initiation at cracked twin boundaries (TBs). Surface characterization demonstrated that TB cracking was mainly ascribed to the incompatible plastic deformation in the twinned area and nearby α-Mg matrix.

9.
Eur Rev Med Pharmacol Sci ; 19(23): 4455, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26698236

RESUMO

The article "Olanzapine inhibits the proliferation and induces the differentiation of glioma stem-like cells through modulating the Wnt signaling pathway in vitro" by Q.-H. Guo, H.-J. Yang, S.-D. Wang, published in Eur Rev Med Pharmacol Sci 2013; 19 (13): 2406-2415 has been withdrawn.

10.
Eur Rev Med Pharmacol Sci ; 19(13): 2406-15, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26214776

RESUMO

OBJECTIVE: Olanzapine, a D2/5-HT2 antagonist, is often used as an atypical antipsychotic drug in clinical. Previous research has found its new pharmacological influence on enhancing the differentiation of neural stem cells (NSCs) to oligodendrocyte-like cells (ODLCs). Glioblastomas are associated with poor prognoses owing to the glioma stem-like cells (GSLCs), which have a great many of similarities with adult NSCs. Hence, in this article, we aim to study the effects and associated mechanisms of olanzapine on GSLCs derived from human U87MG glioblastoma cell lines. MATERIALS AND METHODS: The methyl thiazolyl tetrazolium (MTT) colorimetric assay was conducted to investigate the effects of olanzapine on cell viability of GSLCs. Flow cytometric analysis was applied to study the cell cycle dynamics of GSLCs and Cell Counting Kit-8 (CCK-8) was used to further investigate the proliferation of GSLCs after treated with olanzapine or dimethyl sulfoxide (DMSO) for 48 h. Cell differentiation assay was carried out to study the differentiation of GSLCs and then Image-Pro Plus image analysis was used to measure the protrusion length of the differentiated cells. Furthermore, the confocal [Ca2+]c measurement was conducted to observe the influence of olanzapine on the opening function of Ca2+ channel. After the application of olanzapine for 48 h, RT-PCR was conducted to measure mRNA levels of calcium-sensing receptor (CaSR) and stromal interaction molecule 1 (STIM1), and Western blotting analysis was carried out to examine the expression of myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), CaSR protein, STIM1 protein and ß-catenin protein. RESULTS: Our results demonstrated that olanzapine inhibited the proliferation of GSLCs by arresting cell cycle in G0/G1 phase and facilitated the differentiation of such cells to ODLCs. After treated with olanzapine for 48 h, cells were very sensitive to 100 mM K+ stimulation, with increased spontaneous calcium wave. We also found olanzapine increased the protein expression of MBP and GFAP. In addition, the mRNA transcription and protein expression of CaSR and STIM1 were enhanced after treated with olanzapine for 48h, while the protein expression of ß-catenin was suppressed. CONCLUSIONS: Our results suggest that olanzapine modulates the Wnt signaling pathway through activating the Ca2+ pathway and restraining the ß-catenin pathway, leading to the differentiation of GSLCs to ODLCs. It provides exciting prospects that olanzapine might be a new novel chemotherapeutic modality targeting GSLCs for the treatment of glioblastomas.


Assuntos
Benzodiazepinas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioma , Células-Tronco Neoplásicas/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Glioma/patologia , Humanos , Células-Tronco Neoplásicas/patologia , Olanzapina , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Via de Sinalização Wnt/fisiologia
11.
Eur Rev Med Pharmacol Sci ; 19(12): 2293-6, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26166657

RESUMO

OBJECTIVE: To discuss the effect of combined with intercostal nerve block on analgesia for esophageal cacer after operation. PATIENTS AND METHODS: The total of 80 patients with esophageal cancer as the research object in our hospital from June 2012 to June 2013 were randomly grouped as epidural anesthesia (control group) and general anesthesia and intercostal nerve block combined with application (observation group), whose prognoses were compared. RESULTS: We compared the control group at each time point and the observation group at time T1-T4 with T0. Mean arterial pressure (MAP) had significantly lower performance (mean p < 0.05); at T4, central venus pressure (CVP) of the control group improved significantly (mean p < 0.05), MAP value of the observation group at T3, T4 was significantly lowerthan the control group (mean p < 0.05). The degree of pain 24-48 h after operation of the observation group was lower than the control group, and the difference was statistically significant (p < 0.05). CONCLUSIONS: Application of general anesthesia combined with intercostal nerve block analgesia in esophageal surgery can obtain satisfactory postoperative analgesia.


Assuntos
Anestesia Geral/métodos , Bloqueio Nervoso Autônomo/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Nervos Intercostais , Dor Pós-Operatória/tratamento farmacológico , Adulto , Idoso , Analgesia/métodos , Anestesia Epidural/métodos , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Dor Pós-Operatória/diagnóstico
12.
Genet Mol Res ; 13(4): 8450-7, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25366739

RESUMO

To compare fracture healing therapies, the gene expression profiles of rat fracture samples treated with nail and plate fixation were analyzed at 1 day, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after surgery. The gene expression profiles GSE1685, which include 19 samples, were downloaded from the Gene Expression Omnibus database. After preprocessing, the gene expression profiles were subjected to time series analysis using the Short Time-series Expression Miner software, and the significantly differentially expressed gene (DEG) sets were selected. Further, the distributions of those DEG sets on the corresponding chromosomes were identified using the functional classification tool. Finally, the DEGs were subjected to function and pathway enrichment analysis. DEG analysis indicated that the number of DEGs (854 genes) from nail fixation was significantly lower than that of DEGs (1029 genes) from plate fixation. The DEGs were mainly enriched in cell proliferation, cellular localization, and response to wounding functions. Several critical DEGs expressed during the fracture healing process were screened, and 2 common pathways were enriched for the DEGs in the nail fixation and plate fixation. These DEGs and pathways may be potential targets or predictive markers during fracture healing.


Assuntos
Consolidação da Fratura/genética , Fraturas Ósseas/genética , Transcriptoma , Animais , Modelos Animais de Doenças , Fixação Interna de Fraturas , Fraturas Ósseas/metabolismo , Fraturas Ósseas/cirurgia , Ratos , Transdução de Sinais , Fatores de Tempo
13.
Physiol Res ; 61(5): 543-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23240923

RESUMO

We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1(+)Lin(-)CD45(-)(CXCR(+)) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1alpha levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1(+)CXCR(+) cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI.


Assuntos
Movimento Celular/efeitos dos fármacos , Células-Tronco Embrionárias/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Transplante de Células-Tronco/métodos , Estilbenos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Terapia Combinada , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol , Resultado do Tratamento
14.
Oncogene ; 31(50): 5132-43, 2012 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-22310282

RESUMO

Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain of function and loss of function in glioblastoma-derived stem-like neurospheres, whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2-overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression, and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expressing GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro-invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling, and that optimal antitumor responses to EphB2 targeting may require concurrent use of anti-proliferative agents.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Movimento Celular/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Receptor EphB2/metabolismo , Animais , Neoplasias Encefálicas/genética , Adesão Celular/genética , Adesão Celular/fisiologia , Processos de Crescimento Celular/genética , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/genética , Glioblastoma/enzimologia , Glioblastoma/genética , Humanos , Camundongos , Camundongos SCID , Invasividade Neoplásica , Receptor EphB2/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Phys Chem B ; 109(20): 9892-6, 2005 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-16852196

RESUMO

The growth morphology and mechanism of pentacene films on native Si oxide surface have been studied by using high-resolution electron energy loss spectroscopy (HREELS), X-ray diffraction (XRD), and atomic force microscopy (AFM). Despite the good agreement between our own and the reported XRD results, the previous XRD interpretation that the pentacene molecules are tilt-standing on the substrate cannot explain our HREELS data. The HREELS results show that a substantial portion of the first two layers of pentacene molecules are tilted-standing or randomly oriented, whereas the upper-layer molecules are mostly lying flat to the substrate. AFM reveals that the first two layers of molecules form a flat and smooth surface, but the upper layers show a rough terrace structure with a mean-square roughness equal to the average thickness (without counting the first two layers). This relationship is explained by a theoretical model which assumes the pentacene molecules to remain on a particular molecule layer after arrival. The observed film growth morphology may have significant implication on the performance of electronic devices based on pentacene thin films. A plausible explanation was proposed for the discrepancy between the HREELS-indicated and the XRD-derived molecular orientations.

16.
J Phys Chem B ; 109(21): 10871-9, 2005 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-16852323

RESUMO

A systematic study of the etching behavior of one-dimensional (1-D) Si nanowires (SiNWs) in various HF and NH4F etching solutions is reported. The concentration and pH dependences of the etching time (which is inverse to the "stability") of the SiNWs in these solutions were investigated. A V-shaped bimodal etching curve was observed for HF solutions with concentrations of 0.5-40%. Specifically, SiNWs exhibit high stability in both low (0.5%) and high (40%) concentrations of HF solution, with the lowest stability (i.e., fastest etching rate) occurring at 2% (1 M) HF solution. With NH4F, the time needed to totally etch away the SiNWs sample decreases with increasing concentration (from 1-40%). The opposite is true when the pH of the NH4F solution was maintained at 14. These surprising results were rationalized in terms of "passivation" of the SiNW surfaces by HF or related molecules via hydrogen bonding for Si-H-terminated surfaces in HF solutions (with low pH values) and by NH4(+) ions via ionic bonding for Si-O(-)-terminated surfaces in NH4F solutions (with high pH values), respectively. Furthermore, it was found that SiNWs are stable only in relatively narrow pH ranges in these solutions. When SiNWs are etched with HF, the stability range is pH = 1-2 where the surface moieties are Si-H(x) species (x = 1-3). When SiNWs are etched with NH4F, the stability range is pH = 12-14 where the surface moieties are mainly Si-(O-)x species (x = 1-3). These rationales were confirmed by attenuated total reflection Fourier transform infrared spectroscopy measurements, which showed that, while etching SiNWs with HF gave rise to Si-H(x) surface species, no Si-H(x) species were observed when SiNWs were etched with NH4F. The latter finding is at odds with the corresponding results reported for the two-dimensional (2-D) Si wafers where etching with either HF or NH4F produces Si-H(x) species on the surface. This difference suggests either that the etching mechanisms for NH4F versus HF are different for SiNWs or, more likely, that the Si-H(x) surface species produced in NH4F solutions are so unstable that they are hydrolyzed readily at pH > 4. The similarities and differences of the etching behaviors and the resulting surface speciations between the 1-D SiNWs and the 2-D Si wafers suggest that the nanoscale structures as well as the low dimensionality of SiNWs may have contributed to the rapid hydrolysis of the surface Si-H(x) species in NH4F solutions, especially at high pH values.

17.
J Phys Chem B ; 109(46): 21716-24, 2005 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-16853821

RESUMO

A systematic study of the etching behavior, in terms of three-dimensional profiles, of one-dimensional (1-D) silicon nanowires (SiNWs) in NH(4)F-buffered hydrofluoric acid (BHF) solutions of varying concentrations and pH values and the surface speciations of the resulting etched SiNW surfaces, as characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, is reported. It was found that SiNWs are stable only in relatively narrow pH ranges of the BHF solutions. The results are rationalized in terms of a "double passivation" model. When SiNWs are etched in BHF solutions with pH values of 1-3, the surfaces are passivated with hydrogen (inner layer) giving rise to surface moieties such as Si-H(x) species (x = 1-3); at high HF concentrations, the H-terminated Si surfaces are covered with a hydrogen bonding network of HF and related molecules (oligomers, etc.), providing an outer-layer passivation. When SiNWs are etched in BHF solutions with pH values of 11-14 (by adding a strong base such as NaOH), the surfaces are oxygen-terminated with surface moieties such as Si-(O(-))(x)() species (x = 1-3); at high NH(4)F concentrations, the negatively charged Si surfaces are stabilized by NH(4)(+) ions via ionic bonding, again providing outer-layer passivation. In BHF solutions with pH values of 3-11, the surface speciation, consisting of Si-(OH)(x)(O(-))(y) (x + y = 1-3) species, is unstable and etched away rapidly. The surface speciations of SiNWs etched in various BHF solutions were explored via ATR-FTIR spectroscopy. It was found that, while etching SiNWs with HF-rich BHF solutions with pH < 4 gave rise to Si-H(x)() surface species, no surface Si-H(x) species were observed with SiNWs etched in BHF solutions with pH >/= 4 (HF/NH(4)F /= 4 on the other. These two factors, among others, contribute to the rapid hydrolysis of the surface Si-H(x)() species (and the etching of the SiNWs), particularly in BHF solutions with low HF/NH(4)F ratios and high pH values (pH >/= 4).

18.
Inorg Chem ; 42(7): 2398-404, 2003 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-12665376

RESUMO

Attenuated total reflection Fourier transform infrared (FTIR) spectroscopy was used to characterize the surface species on oxide-free silicon nanowires (SiNWs) after etching with aqueous HF solution. The HF-etched SiNW surfaces were found to be hydrogen-terminated; in particular, three types of silicon hydride species, the monohydride (SiH), the dihydride (SiH(2)), and the trihydride (SiH(3)), had been observed. The thermal stability of the hydrogen-passivated surfaces of SiNWs was investigated by measuring the FTIR spectra after annealing at different elevated temperatures. It was found that hydrogen desorption of the trihydrides occurred at approximately 550 K, and that of the dihydrides occurred at approximately 650 K. At or above 750 K, all silicon hydride species began to desorb from the surfaces of the SiNWs. At around 850 K, the SiNW surfaces were free of silicon hydride species. The stabilities and reactivities of HF-etched SiNWs in air and water were also studied. The hydrogen-passivated surfaces of SiNWs showed good stability in air (under ambient conditions) but relatively poor stability in water. The stabilities and reactivities of the SiNWs are also compared with those of silicon wafers.

19.
Phys Rev Lett ; 87(21): 216802, 2001 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-11736362

RESUMO

The electronic eigenstates of a quantum Hall (QH) system are chiral states. Strong inter-Landau-band mixings among these states can occur when the bandwidth is comparable to the spacing of two adjacent Landau bands. We show that mixing of localized states with opposite chirality can delocalize electronic states. Based on numerical results, we propose the existence of a metallic phase between two adjacent QH phases and between a QH phase and the insulating phase. This result is consistent with nonscaling behaviors observed in recent experiments on a quantum Hall liquid-to-insulator transition.

20.
Artigo em Inglês | MEDLINE | ID: mdl-11444678

RESUMO

1. Using anesthetized cats, the authors examined the noradrenergic modulation of the glutamate induced pressor and depressor responses in various brainstem areas, including pontine gigantocellular tegmental field (FTG), dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline) into FTG, DM and RVLM produced an increase in systemic arterial pressure (SAP) and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and HR. 3. Application of norepinephrine (NE) into the pressor areas (0.05 to 5 nmol) did not alter the resting SAP and HR, but significantly attenuated the Glu-induced pressor response with an order of potency: FTG > DM > RVLM. In the depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and HR, but did not affect the Glu-induced depressor responses. 4. The involvement of different adrenoceptor subtypes was further investigated by application of selective adrenoceptor agonists including phenylephrine (alpha1), clonidine (alpha2), and isoproterenol (beta). Responses to these agonists are similar to those elicited by NE, except that only alpha-adrenoceptor agonists could antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations indicate that NE not only inhibits the pressor mechanisms in various brainstem areas but also elicits a direct depressor response in CVLM. These findings also suggest that NE acts more likely a neurotransmitter, rather than a modulator, in the CVLM.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Tronco Encefálico/fisiologia , Ácido Glutâmico/farmacologia , Norepinefrina/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Gatos , Ácido Glutâmico/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Pressorreceptores/fisiologia , Receptores Adrenérgicos/fisiologia
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