The purpose of the present study was to compare the effects of different doses of ultraviolet radiation A1 （UVA1） on human fibroblast proliferation and collagen level in a mouse model of scleroderma, so as to identi...The purpose of the present study was to compare the effects of different doses of ultraviolet radiation A1 （UVA1） on human fibroblast proliferation and collagen level in a mouse model of scleroderma, so as to identify appropriate irradiation doses for clinical treatment of scleroderma. Monolayer from human fibroblasts was cultured in vitro, and a mouse model of scleroderma was established by subcutaneous injection of 100 μL of 400 μg/mL bleomycin into the back of BALB/c mice for 4 weeks. The mouse models and human fibroblasts were divided into UVA1- exposed （100, 60 and 20 J/cm2） and UVA-unexposed groups. At 0, 24 and 48 h after exposure, cell proliferation and levels of hydroxyproline and collagen were detected. UVA1 irradiation was performed 3 times weekly for 10 weeks, and the pathological changes of skin tissues, skin thickness and collagen level were observed after phototherapy. Cell proliferation and the levels of hydroxyproline and collagen were inhibited after phototherapy, and there was a significant difference between the UVAl-exposed cells and UVAl-unexposed cells （P 〈 0.001）. In addition, UVA1 phototherapy improved dermal sclerosis and softened the skin, and there were significant differences between the high-dose UVA1 group and the model group, and the negative group （P 〈 0.05）. It is concluded that UVA1 radiation can reduce cell proliferation, and decrease hydroxyproline and collagen levels in a dose-dependent manner in vitro. High-dose UVA1 phototherapy has marked therapeutic effect on scleroderma in the mouse model. Decreased collagen level may be related to the reduced number and activity of cells, as well as inhibition of collagen synthesis.展开更多
In order to investigate the effects of verapamil on the proliferation of meningiomas cells in vitro and in vivo, the cultured meningiomas cells were cultured with verapamil at different concentrations for 24 h and the...In order to investigate the effects of verapamil on the proliferation of meningiomas cells in vitro and in vivo, the cultured meningiomas cells were cultured with verapamil at different concentrations for 24 h and the inhibitory effects of verapamil on cell proliferation were observed by MTT method. The meningiomas model was established by implanting the newly removed tumor fragments into the nude mice subcutaneously. The nude mice with tumors were divided into two groups： verapamil-treated group and control group. Tumor volumes were measured and after 12 weeks the tumors were taken out and examined histologically. The expression of proliferating cell nuclear antigen （PCNA） in the tumors was detected by using immunohistochemistry. It was found that verapamil could inhibit the growth of cultured meningiomas cells in a concentration-dependant manner. The inhibitory effect could be observed in the concentration of 1 μmol/L verapamil and the most obvious effects appeared in the concentration of 100 μmol/L. Tumor volume in the verapamiltreated group was obviously smaller than that in the control group （211.40±5.50 vs 163.94±3.62, P〈0.01） and the expression of PCNA was also lower （1.52±0.24 vs 2.86±0.53, P〈0.05）. Tumor inhibition rate was about 22.45%. It was suggested that verapamil could inhibit the proliferation and growth of meningiomas cells in vitro and in vivo.展开更多
Background:Melanoma has poor survival rate owing to its aggressiveness and high rates of metastasis and recurrence.Only few effective therapies are available for metastatic melanoma,so,development of novel anti-metast...Background:Melanoma has poor survival rate owing to its aggressiveness and high rates of metastasis and recurrence.Only few effective therapies are available for metastatic melanoma,so,development of novel anti-metastatic drugs is in urgent need.Cordyceps sinensis is a well-known and common Chinese medicine and has been used as anti-cancer adjuvant treatments for many years.In our study,we aim to evaluate the effects of water extracts of Cordyceps sinensis(WECS)in A375 melanoma cells and in zebrafish model of melanoma metastasis.Methods:Initially,we detected the effect of WECS on the viability in A375 melanoma cells by MTT assay and colony formation assay,and then we detected the effect of WECS on adhesion and metastasis by wound healing assay and Transwell chambers assays.Next,we also explored underlying mechanism by Western blot.Notably,in vivo anti-metastasis assays with A375 zebrafish xenograft model also were performed.Results:As expected,our results found that WECS suppressed proliferation,adhesion and metastasis in A375 melanoma cells via regulating AKT/MMP2/MMP9 pathways and cell cycle.Furthermore,we also confirmed anti-metastasis efficacy of WECS with A375 zebrafish xenograft model.Conclusion:Overall,our results indicate that WECS,as a kind of metastasis inhibitor,may be developed as a new therapeutic strategy for metastatic melanoma treatment.展开更多
miR-504 plays a pivotal role in the progression of oral cancer.However,the underlying mechanism remains elusive in vivo.Here,we find that miR-504 is significantly down-regulated in oral cancer patients.We generate miR...miR-504 plays a pivotal role in the progression of oral cancer.However,the underlying mechanism remains elusive in vivo.Here,we find that miR-504 is significantly down-regulated in oral cancer patients.We generate miR-504 knockout mice(miR-504^(-/-))using CRISPR/Cas9 technology to investigate its impact on the malignant progression of oral cancer under exposure to 4-Nitroquinoline N-oxide(4NQO).We show that the deletion of miR-504 does not affect phenotypic characteristics,body weight,reproductive performance,and survival in mice,but results in changes in the blood physiological and biochemical indexes of the mice.Moreover,with 4NQO treatment,miR-504^(-/-)mice exhibit more pronounced pathological changes char-acteristic of oral cancer.RNA sequencing shows that the differentially expressed genes observed in samples from miR-504^(-/-)mice with oral cancer are involved in regulating cell metabolism,cytokine acti-vation,and lipid metabolism-related pathways.Additionally,these differentially expressed genes are significantly enriched in lipid metabolism pathways that influence immune cell infiltration within the tumor microenvironment,thereby accelerating tumor development progression.Collectively,our results suggest that knockout of miR-504 accelerates malignant progression in 4NQO-induced oral cancer by regulating tumor cell proliferation and lipid metabolism,affecting immune cell infiltration.展开更多
In this chapter we have developed a deterministic model of growth of abnormal cell concentration in a human subject at different positions. The diffusion-reaction Equation has been applied to satisfy growth dynamics ....In this chapter we have developed a deterministic model of growth of abnormal cell concentration in a human subject at different positions. The diffusion-reaction Equation has been applied to satisfy growth dynamics .The whole tumor region is divided into layers which, with the growth of tumor form necrotic, quiescent and region of proliferating of tumor cells. Finite element method for one dimension has been employed for solving the Equations. Here we have taken into account the cellular motility along with proliferative growth ,which is particularly required in case of some of the brain tumors, where motility of gliomas cells differ widely in gray and white matter.展开更多
Gliomas, the most aggressive form of brain cancer, are known for their widespread invasion into the tissue near the tumor lesion. Exponential models, which have been widely used in other types of cancers, cannot be us...Gliomas, the most aggressive form of brain cancer, are known for their widespread invasion into the tissue near the tumor lesion. Exponential models, which have been widely used in other types of cancers, cannot be used for the simulation of tumor growth, due to the diffusive behavior of glioma. Diffusive models that have been proposed in the last two decades seem to better approximate the expansion of gliomas. This paper covers the history of glioma diffusive modelling, starting from the simplified initial model in 90s and describing how this have been enriched to take into account heterogenous brain tissue, anisotropic migration of glioma cells and adjustable proliferation rates. Especially, adjustable proliferation rates are very important for modelling therapy plans and personalising therapy to different patients.展开更多
To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with t...To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups： the rats were treated by 0.9 % NS （n=24, control group）, inosine＋vitamin C （n=40, InV group）, Danshen （n=40, DS group） and 5-FU （n=40, 5-FU group）, respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU （P〈0.01）. No significant difference in protective effect was observed between DS group and lnV group （P〉0.05）. Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine＋vitamin C （P〈0.01）. No significant difference in this regard existed between DS group and 5-FU group （P〉0.05）. The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were lower than those in control group and InV group, with the differences being significant （P〈0.01）. No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF （P〉0.05） but ICAM-1 （P〈0.05）. It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.展开更多
文摘The purpose of the present study was to compare the effects of different doses of ultraviolet radiation A1 （UVA1） on human fibroblast proliferation and collagen level in a mouse model of scleroderma, so as to identify appropriate irradiation doses for clinical treatment of scleroderma. Monolayer from human fibroblasts was cultured in vitro, and a mouse model of scleroderma was established by subcutaneous injection of 100 μL of 400 μg/mL bleomycin into the back of BALB/c mice for 4 weeks. The mouse models and human fibroblasts were divided into UVA1- exposed （100, 60 and 20 J/cm2） and UVA-unexposed groups. At 0, 24 and 48 h after exposure, cell proliferation and levels of hydroxyproline and collagen were detected. UVA1 irradiation was performed 3 times weekly for 10 weeks, and the pathological changes of skin tissues, skin thickness and collagen level were observed after phototherapy. Cell proliferation and the levels of hydroxyproline and collagen were inhibited after phototherapy, and there was a significant difference between the UVAl-exposed cells and UVAl-unexposed cells （P 〈 0.001）. In addition, UVA1 phototherapy improved dermal sclerosis and softened the skin, and there were significant differences between the high-dose UVA1 group and the model group, and the negative group （P 〈 0.05）. It is concluded that UVA1 radiation can reduce cell proliferation, and decrease hydroxyproline and collagen levels in a dose-dependent manner in vitro. High-dose UVA1 phototherapy has marked therapeutic effect on scleroderma in the mouse model. Decreased collagen level may be related to the reduced number and activity of cells, as well as inhibition of collagen synthesis.
文摘In order to investigate the effects of verapamil on the proliferation of meningiomas cells in vitro and in vivo, the cultured meningiomas cells were cultured with verapamil at different concentrations for 24 h and the inhibitory effects of verapamil on cell proliferation were observed by MTT method. The meningiomas model was established by implanting the newly removed tumor fragments into the nude mice subcutaneously. The nude mice with tumors were divided into two groups： verapamil-treated group and control group. Tumor volumes were measured and after 12 weeks the tumors were taken out and examined histologically. The expression of proliferating cell nuclear antigen （PCNA） in the tumors was detected by using immunohistochemistry. It was found that verapamil could inhibit the growth of cultured meningiomas cells in a concentration-dependant manner. The inhibitory effect could be observed in the concentration of 1 μmol/L verapamil and the most obvious effects appeared in the concentration of 100 μmol/L. Tumor volume in the verapamiltreated group was obviously smaller than that in the control group （211.40±5.50 vs 163.94±3.62, P〈0.01） and the expression of PCNA was also lower （1.52±0.24 vs 2.86±0.53, P〈0.05）. Tumor inhibition rate was about 22.45%. It was suggested that verapamil could inhibit the proliferation and growth of meningiomas cells in vitro and in vivo.
基金Ministry of Industry and Information Technology(MIIT)(2016051913)Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine(Natural Medicine)Translational Medicine,Institute of Medical Plant Development,Peking Union Medical College and Chinese Academy of Medical Sciences.
文摘Background:Melanoma has poor survival rate owing to its aggressiveness and high rates of metastasis and recurrence.Only few effective therapies are available for metastatic melanoma,so,development of novel anti-metastatic drugs is in urgent need.Cordyceps sinensis is a well-known and common Chinese medicine and has been used as anti-cancer adjuvant treatments for many years.In our study,we aim to evaluate the effects of water extracts of Cordyceps sinensis(WECS)in A375 melanoma cells and in zebrafish model of melanoma metastasis.Methods:Initially,we detected the effect of WECS on the viability in A375 melanoma cells by MTT assay and colony formation assay,and then we detected the effect of WECS on adhesion and metastasis by wound healing assay and Transwell chambers assays.Next,we also explored underlying mechanism by Western blot.Notably,in vivo anti-metastasis assays with A375 zebrafish xenograft model also were performed.Results:As expected,our results found that WECS suppressed proliferation,adhesion and metastasis in A375 melanoma cells via regulating AKT/MMP2/MMP9 pathways and cell cycle.Furthermore,we also confirmed anti-metastasis efficacy of WECS with A375 zebrafish xenograft model.Conclusion:Overall,our results indicate that WECS,as a kind of metastasis inhibitor,may be developed as a new therapeutic strategy for metastatic melanoma treatment.
基金This work was supported by the National Natural Science Foundation of China(31970513 to G.S.)the Central Government's Guide to Local Science and Technology Development Fund(YDZJSX2022A060 to G.S.)+2 种基金the special funds for Science and Technology Innovation Teams of Shanxi Province(202204051002032 to G.S.)the Shanxi Province Higher Education"BillionProject"Science and Technology Guidance Project(BYJLO16 to G.S.)the Natural Science Foundation of Shanxi Province(20210302124093 to J.G.).
文摘miR-504 plays a pivotal role in the progression of oral cancer.However,the underlying mechanism remains elusive in vivo.Here,we find that miR-504 is significantly down-regulated in oral cancer patients.We generate miR-504 knockout mice(miR-504^(-/-))using CRISPR/Cas9 technology to investigate its impact on the malignant progression of oral cancer under exposure to 4-Nitroquinoline N-oxide(4NQO).We show that the deletion of miR-504 does not affect phenotypic characteristics,body weight,reproductive performance,and survival in mice,but results in changes in the blood physiological and biochemical indexes of the mice.Moreover,with 4NQO treatment,miR-504^(-/-)mice exhibit more pronounced pathological changes char-acteristic of oral cancer.RNA sequencing shows that the differentially expressed genes observed in samples from miR-504^(-/-)mice with oral cancer are involved in regulating cell metabolism,cytokine acti-vation,and lipid metabolism-related pathways.Additionally,these differentially expressed genes are significantly enriched in lipid metabolism pathways that influence immune cell infiltration within the tumor microenvironment,thereby accelerating tumor development progression.Collectively,our results suggest that knockout of miR-504 accelerates malignant progression in 4NQO-induced oral cancer by regulating tumor cell proliferation and lipid metabolism,affecting immune cell infiltration.
文摘In this chapter we have developed a deterministic model of growth of abnormal cell concentration in a human subject at different positions. The diffusion-reaction Equation has been applied to satisfy growth dynamics .The whole tumor region is divided into layers which, with the growth of tumor form necrotic, quiescent and region of proliferating of tumor cells. Finite element method for one dimension has been employed for solving the Equations. Here we have taken into account the cellular motility along with proliferative growth ,which is particularly required in case of some of the brain tumors, where motility of gliomas cells differ widely in gray and white matter.
文摘Gliomas, the most aggressive form of brain cancer, are known for their widespread invasion into the tissue near the tumor lesion. Exponential models, which have been widely used in other types of cancers, cannot be used for the simulation of tumor growth, due to the diffusive behavior of glioma. Diffusive models that have been proposed in the last two decades seem to better approximate the expansion of gliomas. This paper covers the history of glioma diffusive modelling, starting from the simplified initial model in 90s and describing how this have been enriched to take into account heterogenous brain tissue, anisotropic migration of glioma cells and adjustable proliferation rates. Especially, adjustable proliferation rates are very important for modelling therapy plans and personalising therapy to different patients.
文摘To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups： the rats were treated by 0.9 % NS （n=24, control group）, inosine＋vitamin C （n=40, InV group）, Danshen （n=40, DS group） and 5-FU （n=40, 5-FU group）, respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU （P〈0.01）. No significant difference in protective effect was observed between DS group and lnV group （P〉0.05）. Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine＋vitamin C （P〈0.01）. No significant difference in this regard existed between DS group and 5-FU group （P〉0.05）. The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were lower than those in control group and InV group, with the differences being significant （P〈0.01）. No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF （P〉0.05） but ICAM-1 （P〈0.05）. It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.
