About 30% of human breast cancers are human epidermal growth factor receptor 2 （HER2）＋. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation o...About 30% of human breast cancers are human epidermal growth factor receptor 2 （HER2）＋. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2＋ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clini-cal outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the develop-ment of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional com-partimentalization, which allows to combine the specifc target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photo-thermal ablation or in photodynamic therapy have been functionalized in order to match specifcity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2＋ breast cancer and anti-HER2 therapy, in particular deep-ening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2＋ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical prac-tice; however promising results encourage an upcoming translation of this research for the next future.展开更多
The colors presented in ornamental fish determine their acceptability in the market, which is one of the main factors which determine their price. Selecting the fish by only looking at them makes the result analysis b...The colors presented in ornamental fish determine their acceptability in the market, which is one of the main factors which determine their price. Selecting the fish by only looking at them makes the result analysis based in statistics difficult. Thus, it has become necessary to develop a method of quantification for practical use, which will apply minimal stress to the fish while being economically feasible. The proposed method uses a technique which converts the colors of interest to numerical indexes usable in statistical methods of higher precision. The results increase the abilities of fish nutrition researchers aiming to intensify the color characteristics of fish through selective breeding and genetic engineering with the intent of reliably achieving the desired visual characteristics for commercialization.展开更多
AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-a...AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and protein kinase B (AKT) inhibitor XIV. DNA synthesis was measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis. The data were processed to calibrate a mathematical model, based on ordinary differential equations, describing the EGFRmediated signal transduction. RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 mol/L, whereas Capan-1 cells were much more resistant. In both cell lines, MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner, whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib. While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines, BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells. Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR, AKT and ERK in both cell lines with similar kinetics. In BxPC-3 cells, higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed. Independent of the cell line, erlotinib efficiently inhibited phosphorylation of EGFR, AKT and ERK. The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally. CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.展开更多
Glomerular filtration rate （GFR） can be measured （mGFR） after intravenous application of indicators that are eliminated by kidneys or estimated （eGFR） using mathematic equations. We have compared eGFR obtained b...Glomerular filtration rate （GFR） can be measured （mGFR） after intravenous application of indicators that are eliminated by kidneys or estimated （eGFR） using mathematic equations. We have compared eGFR obtained by the chronic kidney diseases epidemiology collaboration （CKD-EPI） and the Modification of diet in renal disease （MDRD） Study equations with GFR measured by technetium-99m diethylene triamine penta-acetic acid （99m^Te-DTPA） renal clearance in different stages of renal diseases in order that obtained results may contribute to more adequate choice of methods for the GFR assessment in relation to the type and stage of kidney disease. The study included a total of 189 participants with diabetes mellitus （DM）, glomerulonephritis （GN）, Balkan endemic nephropathy （BEN） and healthy subjects. 99m^Tc-DTPA clearance （ml/min/1.73 m^2） was calculated from the regression equation based on high correlation between distribution volume of radiopharmaceutical and clearance values obtained by multiple blood samples. For blood sample taken at 3 h and 4 h, clearance was calculated according to the equations： y = -0.0128x^2 ＋ 3.077x - 30.3, and y = -0.00628x^2 ＋ 2.066x - 19.3, where y is clearance, and x is distribution volume. MDRD-GFR （ml/min/l.73 m2） was calculated from equation： 186 × Scr^-1154 × age^-0.203 × 0.742 if female. CKD-EPI-GFR was calculated from equation： 141 × min（Scr/K, 1）^ α ×max（Scr/K, 1）^-1 209 × 0.993age × 1.018 if female, where Scr is serum creatinine, n is 0.7 for females and 0.9 for males, c~ is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/K or 1, and max indicates the maximum of Scr/κ or 1. Irrespective of renal disease, both equations underestimated radionuclide clearance at mGFR 〉 90 ml/min/1.73 m^2 （91.7 ± 18.8 and 88.2 ± 22.0 vs. 121± 19.6, p〈0.0001） and at mGFR 60-89 ml/min/1.73 m^2 （67.1 ±19.9 and 65.8 ± 19.9 vs. 75.8 ± 9.2, p 〈 0.05 and p 〈 0.005）. They were also significantly lower than mGFR in DM patients with GFR 〉_ 90 ml/min/1.73 m^2. In patients with GFR 〉 60 ml/min/1.73 m^2, the median bias of CKD-EPI equation was lower and accuracy （percent of eGFR within 30% of mGFR, P30） was higher than that of MDRD equation. Nevertheless, in DM patients with GFR _〉 90 ml/min the accuracy of the former equation is significantly better than that of MDRD formula. Patients GFR 〈 60 ml/min had the similar bias and accuracy both eGFR equations. As CKD-EPI equation has lesser bias and improved accuracy than MDRD equation in patients with GFR 〉 60 ml/min, we suggest its use for prediction of GFR at higher renal function levels. However, underestimation of renal function by CKD-EPI equation seems not to be quite appropriate in diabetic patients with expected GFR above 90 ml/min because it may miss the patients with glomerular hyperfiltration. Thus, priority may be given to 99m^Tc-DTPA clearance method in the earlier stages of kidney diseases in type 1 diabetes mellitus. At last, in patients with expected GFR 〈 60 ml/min, it is better to monitor disease progression by estimating equations than by 99m^Tc-DTPA renal clearance, due to their simpler implementation.展开更多
文摘About 30% of human breast cancers are human epidermal growth factor receptor 2 （HER2）＋. This particular biological portrait is characterized by the overexpression of HER2 receptor with the subsequent deregulation of downstream pathways, which control cellular survival and proliferation. The most effective treatment for HER2＋ cancer is represented by therapy with HER2-targeted agents. Anti-HER2 therapy dramatically improves clini-cal outcomes, although it shows some limitations in achieving a proper treatment. These drawbacks of HER2-targeted therapy may be overcome with the develop-ment of HER2-targeted drug delivery nanodevices. These nanoparticles possess an internal three-dimensional com-partimentalization, which allows to combine the specifc target recognition with their capability to act as a drug reservoir for the selective delivery of chemotherapics to tumor sites. Moreover, nanoparticles useful in photo-thermal ablation or in photodynamic therapy have been functionalized in order to match specifcity in tumor cell recognition and suitable chemical properties. Here, we summarize the state of the art concerning the HER2＋ breast cancer and anti-HER2 therapy, in particular deep-ening the contribution of the nanomedicine. Description of preclinical studies performed with HER2-targeted nanoparticles for HER2＋ breast cancer therapy will be preceded by an overview on HER2-targeting molecules and nano-conjugation strategies. Further investigation will be necessary to introduce these nano-drugs in clinical prac-tice; however promising results encourage an upcoming translation of this research for the next future.
文摘The colors presented in ornamental fish determine their acceptability in the market, which is one of the main factors which determine their price. Selecting the fish by only looking at them makes the result analysis based in statistics difficult. Thus, it has become necessary to develop a method of quantification for practical use, which will apply minimal stress to the fish while being economically feasible. The proposed method uses a technique which converts the colors of interest to numerical indexes usable in statistical methods of higher precision. The results increase the abilities of fish nutrition researchers aiming to intensify the color characteristics of fish through selective breeding and genetic engineering with the intent of reliably achieving the desired visual characteristics for commercialization.
基金Supported by A grant of the Bundesministerium für Bildung und Forschung through the FORSYS partner program, No.0315255the Helmholtz Society as part of the Systems Biology Network
文摘AIM:To gain insights into the molecular action of erlotinib in pancreatic cancer (PC) cells. METHODS:Two PC cell lines, BxPC-3 and Capan-1, were treated with various concentrations of erlotinib, the specific mitogen-activated protein kinase kinase (MEK) inhibitor U0126, and protein kinase B (AKT) inhibitor XIV. DNA synthesis was measured by 5-bromo-2'-deoxyuridine (BrdU) assays. Expression and phosphorylation of the epidermal growth factor receptor (EGFR) and downstream signaling molecules were quantified by Western blot analysis. The data were processed to calibrate a mathematical model, based on ordinary differential equations, describing the EGFRmediated signal transduction. RESULTS:Erlotinib significantly inhibited BrdU incorporation in BxPC-3 cells at a concentration of 1 mol/L, whereas Capan-1 cells were much more resistant. In both cell lines, MEK inhibitor U0126 and erlotinib attenuated DNA synthesis in a cumulative manner, whereas the AKT pathway-specific inhibitor did not enhance the effects of erlotinib. While basal phosphorylation of EGFR and extracellular signal-regulated kinase (ERK) did not differ much between the two cell lines, BxPC-3 cells displayed a more than five-times higher basal phospho-AKT level than Capan-1 cells. Epidermal growth factor (EGF) at 10 ng/mL induced the phosphorylation of EGFR, AKT and ERK in both cell lines with similar kinetics. In BxPC-3 cells, higher levels of phospho-AKT and phospho-ERK (normalized to the total protein levels) were observed. Independent of the cell line, erlotinib efficiently inhibited phosphorylation of EGFR, AKT and ERK. The mathematical model successfully simulated the experimental findings and provided predictions regarding phosphoprotein levels that could be verified experimentally. CONCLUSION:Our data suggest basal AKT phosphorylation and the degree of EGF-induced activation of AKT and ERK as molecular determinants of erlotinib efficiency in PC cells.
文摘Glomerular filtration rate （GFR） can be measured （mGFR） after intravenous application of indicators that are eliminated by kidneys or estimated （eGFR） using mathematic equations. We have compared eGFR obtained by the chronic kidney diseases epidemiology collaboration （CKD-EPI） and the Modification of diet in renal disease （MDRD） Study equations with GFR measured by technetium-99m diethylene triamine penta-acetic acid （99m^Te-DTPA） renal clearance in different stages of renal diseases in order that obtained results may contribute to more adequate choice of methods for the GFR assessment in relation to the type and stage of kidney disease. The study included a total of 189 participants with diabetes mellitus （DM）, glomerulonephritis （GN）, Balkan endemic nephropathy （BEN） and healthy subjects. 99m^Tc-DTPA clearance （ml/min/1.73 m^2） was calculated from the regression equation based on high correlation between distribution volume of radiopharmaceutical and clearance values obtained by multiple blood samples. For blood sample taken at 3 h and 4 h, clearance was calculated according to the equations： y = -0.0128x^2 ＋ 3.077x - 30.3, and y = -0.00628x^2 ＋ 2.066x - 19.3, where y is clearance, and x is distribution volume. MDRD-GFR （ml/min/l.73 m2） was calculated from equation： 186 × Scr^-1154 × age^-0.203 × 0.742 if female. CKD-EPI-GFR was calculated from equation： 141 × min（Scr/K, 1）^ α ×max（Scr/K, 1）^-1 209 × 0.993age × 1.018 if female, where Scr is serum creatinine, n is 0.7 for females and 0.9 for males, c~ is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/K or 1, and max indicates the maximum of Scr/κ or 1. Irrespective of renal disease, both equations underestimated radionuclide clearance at mGFR 〉 90 ml/min/1.73 m^2 （91.7 ± 18.8 and 88.2 ± 22.0 vs. 121± 19.6, p〈0.0001） and at mGFR 60-89 ml/min/1.73 m^2 （67.1 ±19.9 and 65.8 ± 19.9 vs. 75.8 ± 9.2, p 〈 0.05 and p 〈 0.005）. They were also significantly lower than mGFR in DM patients with GFR 〉_ 90 ml/min/1.73 m^2. In patients with GFR 〉 60 ml/min/1.73 m^2, the median bias of CKD-EPI equation was lower and accuracy （percent of eGFR within 30% of mGFR, P30） was higher than that of MDRD equation. Nevertheless, in DM patients with GFR _〉 90 ml/min the accuracy of the former equation is significantly better than that of MDRD formula. Patients GFR 〈 60 ml/min had the similar bias and accuracy both eGFR equations. As CKD-EPI equation has lesser bias and improved accuracy than MDRD equation in patients with GFR 〉 60 ml/min, we suggest its use for prediction of GFR at higher renal function levels. However, underestimation of renal function by CKD-EPI equation seems not to be quite appropriate in diabetic patients with expected GFR above 90 ml/min because it may miss the patients with glomerular hyperfiltration. Thus, priority may be given to 99m^Tc-DTPA clearance method in the earlier stages of kidney diseases in type 1 diabetes mellitus. At last, in patients with expected GFR 〈 60 ml/min, it is better to monitor disease progression by estimating equations than by 99m^Tc-DTPA renal clearance, due to their simpler implementation.
