Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far fro...Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.展开更多
In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be po...In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be potent p53-MDM2 inhibitors.Further optimization and structure-activity relationship studies were described in the present work.The result revealed that benzyl group on position N1 of imidazole and bromine on C4-phenyl of pyrrolidone showed higher inhibitory activities.In vitro antiproliferative assay demonstrated the potent p53-MDM2 inhibitor 5c with 4-fold selectivity for U2 OS and Saos-2 cells.These data indicated that 4,5-dihydropyrrolo[3,4-c]pyrazol-6（1H）-one moiety is a valuable scaffold for further development of p53-MDM2 inhibitors.展开更多
The objective of this review is the determination of tyramine in 13 nonalcoholic beers (Maoshaieer) of Tehran market and survey of it’s probably interaction with monoamine oxidase inhibitor drugs (MAOIs) has been inv...The objective of this review is the determination of tyramine in 13 nonalcoholic beers (Maoshaieer) of Tehran market and survey of it’s probably interaction with monoamine oxidase inhibitor drugs (MAOIs) has been investigated. Tyramine was at the highest levels in Baltika (111.34 ± 8.19 μg/ml) and at the lowest level in Bitmalt (8.01 ± 2.09 μg/ml). Comparing different flavors of malt drinks, the highest tyramine content was shown for classic or normal flavor (average 72.99 ± 30.87 μg/ml), while the lowest value belonged to cantaloupe flavored drinks (average 10.55 ± 1.29 μg/ml). In our study, it is seen that there is a significant difference between import and Iranian non-alcoholic beers, the import ones has more tyramine than Iranians. A number of 10 kinds of 13 samples interact whit MAOIs in one serving (250 ml) usage 18.50 mg. The highest tyramine content of Iranian ones is 17.74 mg/250ml and for import ones is 27.83 mg/250ml.展开更多
基金supported by Grants from the Italian Association for Cancer Research(IG14532 and 12182 to RG)the Fondazione CARIPLO(No.2011-0614 to MC)
文摘Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.
基金supported in part by the National Natural Science Foundation of China (Nos. 81373331 and 81502978)the Bio-Pharmaceutical Project of Science and Technology of Shanghai (No. 14431902300)Youth grant of Second Military Medical University (No. 2014QN08)
文摘In the past decade,the p53-MDM2 protein-protein interaction by small molecules has been confirmed as a successful strategy for cancer therapy.In our previous work,pyrrolo[3,4-c]pyrazol-6（1H）-ones were found to be potent p53-MDM2 inhibitors.Further optimization and structure-activity relationship studies were described in the present work.The result revealed that benzyl group on position N1 of imidazole and bromine on C4-phenyl of pyrrolidone showed higher inhibitory activities.In vitro antiproliferative assay demonstrated the potent p53-MDM2 inhibitor 5c with 4-fold selectivity for U2 OS and Saos-2 cells.These data indicated that 4,5-dihydropyrrolo[3,4-c]pyrazol-6（1H）-one moiety is a valuable scaffold for further development of p53-MDM2 inhibitors.
文摘The objective of this review is the determination of tyramine in 13 nonalcoholic beers (Maoshaieer) of Tehran market and survey of it’s probably interaction with monoamine oxidase inhibitor drugs (MAOIs) has been investigated. Tyramine was at the highest levels in Baltika (111.34 ± 8.19 μg/ml) and at the lowest level in Bitmalt (8.01 ± 2.09 μg/ml). Comparing different flavors of malt drinks, the highest tyramine content was shown for classic or normal flavor (average 72.99 ± 30.87 μg/ml), while the lowest value belonged to cantaloupe flavored drinks (average 10.55 ± 1.29 μg/ml). In our study, it is seen that there is a significant difference between import and Iranian non-alcoholic beers, the import ones has more tyramine than Iranians. A number of 10 kinds of 13 samples interact whit MAOIs in one serving (250 ml) usage 18.50 mg. The highest tyramine content of Iranian ones is 17.74 mg/250ml and for import ones is 27.83 mg/250ml.
