Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotro...Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.展开更多
Objective:To investigate the relationship between dynamic contrast-enhanced MRI parameters and tumor angiogenesis in peripheral pulmonary adenocarcinoma.Methods:Thirty-seven patients with pathologic proved pulmonary a...Objective:To investigate the relationship between dynamic contrast-enhanced MRI parameters and tumor angiogenesis in peripheral pulmonary adenocarcinoma.Methods:Thirty-seven patients with pathologic proved pulmonary adenocarcinoma underwent dynamic contrast-enhanced MR Imaging. Microvessel density(MVD) was counted and vascular endothelial growth factor(VEGF) expression was assessed with immunohistochemical method. Dynamic contrast-enhanced MRI-derived parameters, such as peak height(PH), steepest slope(SS), maximum enhancement rate(E max),enhancement rate at 1-6 minutes(E 1-6), were calculated and compared with MVD in pulmonary adenocarcinoma. And the parameters were also compared between VEGF-positive and VEGF-negative pulmonary adenocarcinoma. Results:The microvessel density was 68.31±19.84 in 37 pulmonary adenocarcinoma. The PH, SS, E max, E 1-6 correlated positively with MVD respectively(P<0.001). The strongest relationship was found between SS and MVD(r=0.827,P<0.001). There was a significant difference between MVD of VEGF-positive pulmonary adenocarcinoma (79.47±21.35) and MVD of VEGF-negative pulmonary adenocarcinoma (43.16±17.85)(P<0.001). All the parameters in VEGF-positive pulmonary adenocarcinoma were higher than those in VEGF-negative pulmonary adenocarcinao(P<0.001). Conclusion: Dynamic contrast-enhanced MRI-derived parameters of pulmonary adenocarcinoma correlated positively with MVD. The parameters in VEGF-positive pulmonary adenocarcinoma were higher than those in VEGF-negative pulmonary adenocarcinoma(P<0.001).展开更多
BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tu...BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.展开更多
基金supported by the research start-up and the MWU’s intramural grant(to MF)the Italian MURST-MIUR foundation(to SG and IP)
文摘Neurotrophins play a major role in the regulation of neuronal growth such as neurite sprouting or regeneration in response to nerve injuries. The role of nerve growth factor, neurotrophin-3, and brain-derived neurotrophic factor in maintaining the survival of peripheral neurons remains poorly understood. In regenerative medicine, different modalities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. This study was to investigate the influence of nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor on the growth of neurites using two in vitro models of dorsal root ganglia explants and dorsal root ganglia-derived primary cell dissociated cultures. Quantitative data showed that the total neurite length and tortuosity were differently influenced by trophic factors. Nerve growth factor and, indirectly, brain-derived neurotrophic factor stimulate the tortuous growth of sensory fibers and the formation of cell clusters. Neurotrophin-3, however, enhances neurite growth in terms of length and linearity allowing for a more organized and directed axonal elongation towards a peripheral target compared to the other growth factors. These findings could be of considerable importance for any clinical application of neurotrophic factors in peripheral nerve regeneration. Ethical approval was obtained from the Regione Piemonte Animal Ethics Committee ASLTO1(file # 864/2016-PR) on September 14, 2016.
文摘Objective:To investigate the relationship between dynamic contrast-enhanced MRI parameters and tumor angiogenesis in peripheral pulmonary adenocarcinoma.Methods:Thirty-seven patients with pathologic proved pulmonary adenocarcinoma underwent dynamic contrast-enhanced MR Imaging. Microvessel density(MVD) was counted and vascular endothelial growth factor(VEGF) expression was assessed with immunohistochemical method. Dynamic contrast-enhanced MRI-derived parameters, such as peak height(PH), steepest slope(SS), maximum enhancement rate(E max),enhancement rate at 1-6 minutes(E 1-6), were calculated and compared with MVD in pulmonary adenocarcinoma. And the parameters were also compared between VEGF-positive and VEGF-negative pulmonary adenocarcinoma. Results:The microvessel density was 68.31±19.84 in 37 pulmonary adenocarcinoma. The PH, SS, E max, E 1-6 correlated positively with MVD respectively(P<0.001). The strongest relationship was found between SS and MVD(r=0.827,P<0.001). There was a significant difference between MVD of VEGF-positive pulmonary adenocarcinoma (79.47±21.35) and MVD of VEGF-negative pulmonary adenocarcinoma (43.16±17.85)(P<0.001). All the parameters in VEGF-positive pulmonary adenocarcinoma were higher than those in VEGF-negative pulmonary adenocarcinao(P<0.001). Conclusion: Dynamic contrast-enhanced MRI-derived parameters of pulmonary adenocarcinoma correlated positively with MVD. The parameters in VEGF-positive pulmonary adenocarcinoma were higher than those in VEGF-negative pulmonary adenocarcinoma(P<0.001).
文摘BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.
