China’s pharmaceuticals industry is one of the industries making use of foreign funds and running three kinds of foreign-funded enterprises from an early date. In 1980, it signed a contract with the Japanese Pharmace...China’s pharmaceuticals industry is one of the industries making use of foreign funds and running three kinds of foreign-funded enterprises from an early date. In 1980, it signed a contract with the Japanese Pharmaceu-tical Enterprise to establish the China Otsuka Pharmaceuticals Co. Ltd.---the first joint venture in China’s pharma-ceuticals industry. According to incom-展开更多
Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better appro...Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.展开更多
Jujube is one of the most produced dried fruits in China,and it is also a traditional Chinese medicine that enhances immunity and has anti-cancer activity.Jujube fruit is rich in phenolic compounds,but few reports are...Jujube is one of the most produced dried fruits in China,and it is also a traditional Chinese medicine that enhances immunity and has anti-cancer activity.Jujube fruit is rich in phenolic compounds,but few reports are available on its biological activities.To evaluate the biological activities of the phenolic compounds in dried jujube fruit,the composition and content of metabolites in dried jujube fruit were determined by metabolomics,and the antibacterial and anticancer activities of the phenolic compounds were analyzed in dried jujube fruit.The results showed that 463 compounds were identified in dried‘Junzao’fruit,including 102 phenolic compounds.The in vitro activity test showed that the jujube phenolic metabolites had extensive antibacterial effects and caused disruption and nuclear sclerosis of hepatocellular carcinoma(HepG2)cells.Canonical correlation analysis showed that total phenolic content,quercetin-3-rutinose,and procyanidin B1 were the main active antibacterial and anticancer components.The study provides data supporting the application of dried jujube fruit in the development of functional foods,pharmaceuticals and cosmetics.展开更多
Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeabil...Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides.This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling.These luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without lidocaine.Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier integrity.The two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar extent.The data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular mechanism-of-action.Further,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal hypotonicity.In contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.This suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.展开更多
文摘China’s pharmaceuticals industry is one of the industries making use of foreign funds and running three kinds of foreign-funded enterprises from an early date. In 1980, it signed a contract with the Japanese Pharmaceu-tical Enterprise to establish the China Otsuka Pharmaceuticals Co. Ltd.---the first joint venture in China’s pharma-ceuticals industry. According to incom-
文摘Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.
基金supported by The National Key Research and Development Program of China(2018YFD1000607)National Natural Science Foundation of China(32171839 and 32101564)The earmarked fund of Xinjiang Jujube Industrial Technology System(XJCYTX-01).
文摘Jujube is one of the most produced dried fruits in China,and it is also a traditional Chinese medicine that enhances immunity and has anti-cancer activity.Jujube fruit is rich in phenolic compounds,but few reports are available on its biological activities.To evaluate the biological activities of the phenolic compounds in dried jujube fruit,the composition and content of metabolites in dried jujube fruit were determined by metabolomics,and the antibacterial and anticancer activities of the phenolic compounds were analyzed in dried jujube fruit.The results showed that 463 compounds were identified in dried‘Junzao’fruit,including 102 phenolic compounds.The in vitro activity test showed that the jujube phenolic metabolites had extensive antibacterial effects and caused disruption and nuclear sclerosis of hepatocellular carcinoma(HepG2)cells.Canonical correlation analysis showed that total phenolic content,quercetin-3-rutinose,and procyanidin B1 were the main active antibacterial and anticancer components.The study provides data supporting the application of dried jujube fruit in the development of functional foods,pharmaceuticals and cosmetics.
文摘Transcellular permeation enhancers are known to increase the intestinal permeability of enalaprilat,a 349 Da peptide,but not hexarelin(887 Da).The primary aim of this paper was to investigate if paracellular permeability enhancers affected the intestinal permeation of the two peptides.This was investigated using the rat single-pass intestinal perfusion model with concomitant blood sampling.These luminal compositions included two paracellular permeation enhancers,chitosan(5 mg/mL) and ethylenediaminetetraacetate(EDTA,1 and 5 mg/mL),as well as low luminal tonicity(100 mOsm) with or without lidocaine.Effects were evaluated by the change in lumen-to-blood permeability of hexarelin and enalaprilat,and the blood-to-lumen clearance of ^(51)chromium-labeled EDTA(CL_(Cr-EDTA)),a clinical marker for mucosal barrier integrity.The two paracellular permeation enhancers increased the mucosal permeability of both peptide drugs to a similar extent.The data in this study suggests that the potential for paracellular permeability enhancers to increase intestinal absorption of hydrophilic peptides with low molecular mass is greater than for those with transcellular mechanism-of-action.Further,the mucosal blood-to-lumen flux of ^(51)Cr-EDTA was increased by the two paracellular permeation enhancers and by luminal hypotonicity.In contrast,luminal hypotonicity did not affect the lumen-to-blood transport of enalaprilat and hexarelin.This suggests that hypotonicity affects paracellular solute transport primarily in the mucosal crypt region,as this area is protected from luminal contents by a constant water flow from the crypts.
