BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散...随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散及斜率尽可能低,从而使色散管理成本降到最低的新型单模光纤.我们设计和计算了这种新型的光纤的结构并对其性能参数进行了分析和讨论.展开更多
The objective of this study is to improve the performance of semi-empirical radar backscatter models, which are mainly used in microwave remote sensing (Oh 1992, Oh 2004 and Dubois). The study is based on satellite an...The objective of this study is to improve the performance of semi-empirical radar backscatter models, which are mainly used in microwave remote sensing (Oh 1992, Oh 2004 and Dubois). The study is based on satellite and ground data collected on bare soil surfaces during the Multispectral Crop Monitoring experimental campaign of the CESBIO laboratory in 2010 over an agricultural region in southwestern France. The dataset covers a wide range of soil (viewing top soil moisture, surface roughness and texture) and satellite (at different frequencies: X-, C- and L-bands, and different incidence angles: 24.3° to 53.3°) configurations. The proposed methodology consists in identifying and correcting the residues of the models, depending on the surface properties (roughness, moisture, texture) and/or sensor characteristics (frequency, incidence angle). Finally, one model has been retained for each frequency domain. Results show that the enhancements of the models significantly increase the simulation performances. The coefficient of correlation increases of 23% in mean and the simulation errors (RMSE) are reduced to below 2 dB (at the X and C-bands) and to 1 dB at the L-band, compared to the initial models. At the X- and C-bands, the best performances of the modified models are provided by Dubois, whereas Oh 2004 is more suitable for the L-band (r is equal to 0.69, 0.65 and 0.85). Moreover, the modified models of Oh 1992 and 2004 and Dubois, developed in this study, offer a wider domain of validity than the initial formalism and increase the capabilities of retrieving the backscattering signal in view of applications of such approaches to stronglycontrasted agricultural surface states.展开更多
BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual c...BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β).Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway.In this study,we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of HCC.METHODS:Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3,Smad4,pSmad3C (S423/425),pSmad3L (T179),pSmad3L (S204),and pSmad3L (S213).Disease-specific death was defined as 1) tumor occupying more than 80% of the liver,2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation,3) obstructive jaundice due to tumor,4) distant metastases,or 5) variceal hemorrhage with PVTT proximal to the first bifurcation.At the time of analysis,tumor recurrence was detected in 184 (67.6%) patients,and 96 (35.3%) had died of HCC.RESULTS:Nuclear and cytoplasmic localization of Smad3,and nuclear localization of Smad4 were observed in 18.0%,9.9%,and 9.2% of HCCs,respectively.The rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation:pSmad3C (S423/425) 8.1%,pSmad3L (T179) 2.6%,pSmad3L (S204) 2.2%,and pSmad3L (S213) 10.3%.Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free survival.pSmad3L (S213) (P=0.006),intrahepatic metastasis,multicentric occurrence,and liver cirrhosis were independent predictors of shorter recurrence- free survival.Cytoplasmic Smad3 (P=0.006),larger tumor size,and intrahepatic metastasis were independent predictors of shorter disease-specific survival.Only pSmad3L (S213) did not show an unfavorable influence on recurrence-free survival (P=0.331) on univariate analysis.CONCLUSIONS:pSmad3C (S423/425),pSmad3L (S213),and Smad3 may be predictors of prognosis in HCC patients after curative hepatectomy.pSmad3C (S423/425) and pSmad3L (S213) may be used as immunohistochemical biomarkers to identify patients with a high risk of recurrence.展开更多
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘随着光通信技术的发展,各种现有的单模光纤已不能满足宽带光传输密集波分复用(DWDM)系统传输的要求,S C L三波段传输新型单模光纤是在1460～1625nm的波长范围内具有足够大的色散以抑制四波混频效应、交叉相位调制等非线性效应,又使色散及斜率尽可能低,从而使色散管理成本降到最低的新型单模光纤.我们设计和计算了这种新型的光纤的结构并对其性能参数进行了分析和讨论.
文摘The objective of this study is to improve the performance of semi-empirical radar backscatter models, which are mainly used in microwave remote sensing (Oh 1992, Oh 2004 and Dubois). The study is based on satellite and ground data collected on bare soil surfaces during the Multispectral Crop Monitoring experimental campaign of the CESBIO laboratory in 2010 over an agricultural region in southwestern France. The dataset covers a wide range of soil (viewing top soil moisture, surface roughness and texture) and satellite (at different frequencies: X-, C- and L-bands, and different incidence angles: 24.3° to 53.3°) configurations. The proposed methodology consists in identifying and correcting the residues of the models, depending on the surface properties (roughness, moisture, texture) and/or sensor characteristics (frequency, incidence angle). Finally, one model has been retained for each frequency domain. Results show that the enhancements of the models significantly increase the simulation performances. The coefficient of correlation increases of 23% in mean and the simulation errors (RMSE) are reduced to below 2 dB (at the X and C-bands) and to 1 dB at the L-band, compared to the initial models. At the X- and C-bands, the best performances of the modified models are provided by Dubois, whereas Oh 2004 is more suitable for the L-band (r is equal to 0.69, 0.65 and 0.85). Moreover, the modified models of Oh 1992 and 2004 and Dubois, developed in this study, offer a wider domain of validity than the initial formalism and increase the capabilities of retrieving the backscattering signal in view of applications of such approaches to stronglycontrasted agricultural surface states.
文摘BACKGROUND:Progression of hepatocellular carcinoma (HCC) often leads to vascular invasion and intrahepatic metastasis,which correlate with recurrence after surgical treatment and poor prognosis.HCC may be an unusual cancer affected by continuous inflammation that can lead to consistent upregulation of transforming growth factor-β (TGF-β).Chronic inflammation shifts hepatocytic TGF-β signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway.In this study,we investigated the functional roles of Smad3 and its phosphoisoforms in the progression of HCC.METHODS:Tumor tissue microarrays of samples from 272 HCC patients who underwent curative surgical resection were used to detect the expression of Smad3,Smad4,pSmad3C (S423/425),pSmad3L (T179),pSmad3L (S204),and pSmad3L (S213).Disease-specific death was defined as 1) tumor occupying more than 80% of the liver,2) portal venous tumor thrombus (PVTT) proximal to the second bifurcation,3) obstructive jaundice due to tumor,4) distant metastases,or 5) variceal hemorrhage with PVTT proximal to the first bifurcation.At the time of analysis,tumor recurrence was detected in 184 (67.6%) patients,and 96 (35.3%) had died of HCC.RESULTS:Nuclear and cytoplasmic localization of Smad3,and nuclear localization of Smad4 were observed in 18.0%,9.9%,and 9.2% of HCCs,respectively.The rates of Smad3 phosphoisoform-immunoreactive HCC varied according to the location of phosphorylation:pSmad3C (S423/425) 8.1%,pSmad3L (T179) 2.6%,pSmad3L (S204) 2.2%,and pSmad3L (S213) 10.3%.Multivariate analyses revealed that pSmad3C (S423/425) (P=0.022) was an independent predictor of longer recurrence-free survival.pSmad3L (S213) (P=0.006),intrahepatic metastasis,multicentric occurrence,and liver cirrhosis were independent predictors of shorter recurrence- free survival.Cytoplasmic Smad3 (P=0.006),larger tumor size,and intrahepatic metastasis were independent predictors of shorter disease-specific survival.Only pSmad3L (S213) did not show an unfavorable influence on recurrence-free survival (P=0.331) on univariate analysis.CONCLUSIONS:pSmad3C (S423/425),pSmad3L (S213),and Smad3 may be predictors of prognosis in HCC patients after curative hepatectomy.pSmad3C (S423/425) and pSmad3L (S213) may be used as immunohistochemical biomarkers to identify patients with a high risk of recurrence.
