Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment reg...Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.展开更多
Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in a...Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in antiviral therapy is seldom reported.Here,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/mL.Furthermore,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs.Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice.Importantly,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory factors.In conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.展开更多
文摘Background:Osteosarcoma is the most common malignant primary bone tumor.The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy.Moreover,current treatment regimens bear a significant risk of serious side effects.Thus,there is an unmet clinical need for effective therapies with improved safety profiles.Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.Methods:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day zero.Animals were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal administration.Results:After 35 days,mice were euthanized,and the tumors were harvested for analysis.Eighteen mice were excluded from the analysis due to complications.Body weight was significantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this group.Intraperitoneal tumor weight was significantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the control.No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine.There were no significant differences in microvessel density or mitotic rate between treatment groups.Reduced body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is preferable.Conclusions:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited.Moreover,its toxic profile grants further evaluation.Given these observations,further research is necessary to refine the use of taurolidine in osteosarcoma treatment.
基金supported by the Chinese National Natural Science Foundation of China(grant number:31970502)the National Key Research and Development Program of China(2021YFC2301701,2020ZX10001-016-003 and ZX10304402-003-006).
文摘Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of microorganisms.However,its application in antiviral therapy is seldom reported.Here,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/mL.Furthermore,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice lungs.Administration of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected mice.Importantly,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory factors.In conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.
