Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several di...Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor (VEGFR)-inhibitor axitinib.展开更多
Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for L...Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.展开更多
Objective To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation.Methods Twenty rats were exposed to h...Objective To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation.Methods Twenty rats were exposed to hypoxic conditions for 3 weeks. Ten rats were used as normoxic controls. We administered Tet pulmonary targeting microspheres to 10 hypoxic rats and Tet aqueous solution to 10 hypoxic rats and the 10 control rats. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. Results Rats exposed to hypoxia developed pulmonary hypertension. The decrease in mPAP in rats treated with Tet pulmonary targeting microspheres was significantly greater than that in rats receiving Tet aqueous solution (P【0.05), and the effects were longer with Tet pulmonary targeting microspheres. Moreover, Tet pulmonary targeting microspheres, unlike Tet aqueous solution, did not decrease mSBP.Conclusion Tet pulmonary targeting microspheres were more effective than Tet aqueous solution in treating hypoxic pulmonary hypertension and acted selectively on the pulmonary circulation.展开更多
Traditional Chinese medicine(TCM) holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantag...Traditional Chinese medicine(TCM) holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, "network target", which is different from the Western medicine's "onetarget" concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM's potential in current medical systems.展开更多
Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel.It is commonly used as an expectorant and supplementary anti-cancer drug.β-Glucosidase is an enzyme that hydrolyzes t...Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel.It is commonly used as an expectorant and supplementary anti-cancer drug.β-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose.Upon their interaction,β-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid,which inhibits cytochrome C oxidase,the terminal enzyme in the mitochondrial respiration chain,and suspends adenosine triphosphate synthesis,resulting in cell death.Hydrocyanic acid is a cell-cycle-stage-nonspecific agent that kills cancer cells.Thus,β-glucosidase can be coupled with a tumor-specific monoclonal antibody.β-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a kil ing effect.β-Glucosidase is injected intravenously and recognizes cancer-cel-surface antigens with the help of an antibody.The prodrug amarogentin is infused after β-glucosidase has reached the target position.Coupling of cell membrane peptides with β-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein.The Chinese medicine amarogentin and β-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed.展开更多
基金the Heinrich and Alma Vogelsang Foundation for financial support in the form of a graduation scholarship
文摘Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor (VEGFR)-inhibitor axitinib.
基金J. Chad Brenner received funding from NIH (Grants No. U01DE025184 and P30: CA046592 S1)Andrew C. Birkeland and Rebecca Hoesli received support from University of Michigan Otolaryngology Resident Research (Grant No. T32DC005356)Megan L. Ludwig was supported by NIH (Grant No. T-32-GM007315)
文摘Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.
文摘Objective To assess the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and evaluate its selective action on pulmonary circulation.Methods Twenty rats were exposed to hypoxic conditions for 3 weeks. Ten rats were used as normoxic controls. We administered Tet pulmonary targeting microspheres to 10 hypoxic rats and Tet aqueous solution to 10 hypoxic rats and the 10 control rats. Mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, and mean systemic blood pressure (mSBP) was measured by left femoral catheterization. Results Rats exposed to hypoxia developed pulmonary hypertension. The decrease in mPAP in rats treated with Tet pulmonary targeting microspheres was significantly greater than that in rats receiving Tet aqueous solution (P【0.05), and the effects were longer with Tet pulmonary targeting microspheres. Moreover, Tet pulmonary targeting microspheres, unlike Tet aqueous solution, did not decrease mSBP.Conclusion Tet pulmonary targeting microspheres were more effective than Tet aqueous solution in treating hypoxic pulmonary hypertension and acted selectively on the pulmonary circulation.
基金Supported by the National Natural Science Foundation of China(No.81225025 and 91229201)
文摘Traditional Chinese medicine(TCM) holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, "network target", which is different from the Western medicine's "onetarget" concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM's potential in current medical systems.
文摘Amarogentin is an efficacious Chinese herbal medicine and a component of the bitter apricot kernel.It is commonly used as an expectorant and supplementary anti-cancer drug.β-Glucosidase is an enzyme that hydrolyzes the glycosidic bond between aryl and saccharide groups to release glucose.Upon their interaction,β-glucosidase catalyzes amarogentin to produce considerable amounts of hydrocyanic acid,which inhibits cytochrome C oxidase,the terminal enzyme in the mitochondrial respiration chain,and suspends adenosine triphosphate synthesis,resulting in cell death.Hydrocyanic acid is a cell-cycle-stage-nonspecific agent that kills cancer cells.Thus,β-glucosidase can be coupled with a tumor-specific monoclonal antibody.β-Glucosidase can combine with cancer-cell-surface antigens and specifically convert amarogentin to an active drug that acts on cancer cells and the surrounding antibodies to achieve a kil ing effect.β-Glucosidase is injected intravenously and recognizes cancer-cel-surface antigens with the help of an antibody.The prodrug amarogentin is infused after β-glucosidase has reached the target position.Coupling of cell membrane peptides with β-glucosidase allows the enzyme to penetrate capillary endothelial cells and clear extracellular deep solid tumors to kill the cells therein.The Chinese medicine amarogentin and β-glucosidase will become an important treatment for various tumors when an appropriate monoclonal antibody is developed.