Background: D-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of D-Limonene ...Background: D-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of D-Limonene on a K562-induced model of chronic myeloid leukemia(CML) in C57 BL/6 mice.Method: The tail vein injection model of K562 cells in immunocompromised C57 BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with D-Limonene and evaluated for haematological parameters. We also evaluated the effect of D-Limonene on angiogenesis using the chick chorioallantoic membrane(CAM) assay.Results: In a complete blood count, a significant dose-dependent reduction in white blood cell, neutrophil and lymphocyte counts, but an elevation in red blood cell count and haemoglobin content was observed with D-Limonene treatment compared to the disease control or untreated group. In the CAM assay, D-Limonene produced a significant dose-dependent reduction in number of blood vessels in treatment groups compared to the vehicle-treated group.Conclusion: These studies suggest promising anti-leukemic and anti-angiogenic effects of D-Limonene in the treatment of CML.展开更多
Chorioallantoic membrane(CAM)is responsible for respiratory gas exchange,eggshell calcium transport,embryonic acid-base equilibrium,allantoic ion,and water reabsorption during avian embryonic development.To further un...Chorioallantoic membrane(CAM)is responsible for respiratory gas exchange,eggshell calcium transport,embryonic acid-base equilibrium,allantoic ion,and water reabsorption during avian embryonic development.To further understand the timing of CAM gene expression during chick embryonic development,especially the calcium absorption mechanism,transcriptome quantitative comparative analysis was conducted on chick CAM during the embryonic period(E)of 9,13,17,and 20 days.A total of 6378 differentially expressed genes(DEGs)were identified.Functional enrichment analysis of DEGs showed that CAM DEGs were mainly involved in biological processes such as"ion transport regulation","immune response"and"cell cycle".Time series analysis of the differential genes showed that the functional cells of CAM began to proliferate and differentiate at E9 and the calcium content of egg embryo increased significantly at E13.Simultaneously,the observation of the ultrastructure of the eggshell showed that the interstice of the fiber layer was enlarged at E13,and the mastoid layer was partly exposed.Therefore,it is preliminarily inferred that CAM calcium transport starts at E13,and genes such as TRPV6,S100 A10,and RANKL cooperate to regulate calcium release and transport.展开更多
Cancer of the urological system commonly occurs in the kidney,bladder,and prostate gland.The clear cell subtype of renal cell carcinoma(ccRCC)constitutes the great majority of kidney cancer.Metastatic ccRCC portends a...Cancer of the urological system commonly occurs in the kidney,bladder,and prostate gland.The clear cell subtype of renal cell carcinoma(ccRCC)constitutes the great majority of kidney cancer.Metastatic ccRCC portends a very poor outcome with no effective treatment available.Prostate cancer is the most common cancer in males in the US.Despite recent advances in selective kinase inhibitors and immunotherapies,the rate of developing new treatment from bench to bedside is slow.A time-consuming step is at the animal drug testing stage,in which the mouse model is the gold standard.In the pursuit to streamline the in vivo cancer biology research and drug development,we explored the feasibility of the chicken chorioallantoic membrane(CAM)model to establish xenografts.The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice.We generated CAM xenografts from ccRCC,bladder and prostate cancer,with established cancer cell lines and freshly isolated patient-derived tissues,either as primary tumor cells or small pieces of tumors.The successful CAM engraftment rate from the different tumor sources is 70%or above.Using our previously established metastatic ccRCC mouse model,we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice.Taken together,CAM can serve as a valuable platform to establish new patient-derived xenografts(PDXs)to study tumor biology,thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.展开更多
文摘Background: D-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of D-Limonene on a K562-induced model of chronic myeloid leukemia(CML) in C57 BL/6 mice.Method: The tail vein injection model of K562 cells in immunocompromised C57 BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with D-Limonene and evaluated for haematological parameters. We also evaluated the effect of D-Limonene on angiogenesis using the chick chorioallantoic membrane(CAM) assay.Results: In a complete blood count, a significant dose-dependent reduction in white blood cell, neutrophil and lymphocyte counts, but an elevation in red blood cell count and haemoglobin content was observed with D-Limonene treatment compared to the disease control or untreated group. In the CAM assay, D-Limonene produced a significant dose-dependent reduction in number of blood vessels in treatment groups compared to the vehicle-treated group.Conclusion: These studies suggest promising anti-leukemic and anti-angiogenic effects of D-Limonene in the treatment of CML.
基金financially supported by the Foundation of Guizhou Educational Committee(No.KY[2021]008 and No.KY[2020]014)the National Natural Science Foundation of China(No.31871732)。
文摘Chorioallantoic membrane(CAM)is responsible for respiratory gas exchange,eggshell calcium transport,embryonic acid-base equilibrium,allantoic ion,and water reabsorption during avian embryonic development.To further understand the timing of CAM gene expression during chick embryonic development,especially the calcium absorption mechanism,transcriptome quantitative comparative analysis was conducted on chick CAM during the embryonic period(E)of 9,13,17,and 20 days.A total of 6378 differentially expressed genes(DEGs)were identified.Functional enrichment analysis of DEGs showed that CAM DEGs were mainly involved in biological processes such as"ion transport regulation","immune response"and"cell cycle".Time series analysis of the differential genes showed that the functional cells of CAM began to proliferate and differentiate at E9 and the calcium content of egg embryo increased significantly at E13.Simultaneously,the observation of the ultrastructure of the eggshell showed that the interstice of the fiber layer was enlarged at E13,and the mastoid layer was partly exposed.Therefore,it is preliminarily inferred that CAM calcium transport starts at E13,and genes such as TRPV6,S100 A10,and RANKL cooperate to regulate calcium release and transport.
基金This study was supported by National Cancer Institute/-National Institutes of Health(Grant No.1R21CA216770)UC Tobacco-related Disease Research Program(Grant No.27IR-0016),Department of Defense(Grant No.W81XWH-15-1-0256)Cancer Research Coordinating Committee(Grant No.CRC15-380768)to L.W.UCLA institutional support grant support included:UCLA JCCC grant no.P30CA016042,and UCLA CTSI grant no.UL1TR001881(to L.W.).We thank UCLA Translational Pathology Core Laboratory for the preparation of tumor samples.
文摘Cancer of the urological system commonly occurs in the kidney,bladder,and prostate gland.The clear cell subtype of renal cell carcinoma(ccRCC)constitutes the great majority of kidney cancer.Metastatic ccRCC portends a very poor outcome with no effective treatment available.Prostate cancer is the most common cancer in males in the US.Despite recent advances in selective kinase inhibitors and immunotherapies,the rate of developing new treatment from bench to bedside is slow.A time-consuming step is at the animal drug testing stage,in which the mouse model is the gold standard.In the pursuit to streamline the in vivo cancer biology research and drug development,we explored the feasibility of the chicken chorioallantoic membrane(CAM)model to establish xenografts.The CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised mice.We generated CAM xenografts from ccRCC,bladder and prostate cancer,with established cancer cell lines and freshly isolated patient-derived tissues,either as primary tumor cells or small pieces of tumors.The successful CAM engraftment rate from the different tumor sources is 70%or above.Using our previously established metastatic ccRCC mouse model,we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in mice.Taken together,CAM can serve as a valuable platform to establish new patient-derived xenografts(PDXs)to study tumor biology,thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.
