Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challen...Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.展开更多
Aim:Strong evidence reveals important differences between cancers in the proximal vs.distal colon.Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several importan...Aim:Strong evidence reveals important differences between cancers in the proximal vs.distal colon.Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several important limitations.We explored whether there were regional differences in the location of murine colon cancers and assessed the utility of murine models to explore the biological basis for such differences.Methods:We re-analyzed data from our previous studies to assess the regional distribution of murine colon cancer.In survival surgery experiments,we injected HT-29 human colon cancer cells into the wall of the cecum or distal colon of Nu(NCr)-Foxn1 nu or NOD.Cg-Prkdc scid Il2rg Tim1Wji/SzJ mice and compared the development of primary tumors and metastases.Results:Within 7-17 weeks after intramural cecal injection of HT-29 cells,eight mice failed to develop solid primary tumors or metastases.In contrast,within four weeks after cell injection into the distal colon,13 mice developed metastases-12 mice developed subcutaneous metastases;of these,four developed liver metastases and one developed both liver and lung metastases.One mouse developed liver metastases only.Histological examination confirmed these lesions were adenocarcinomas.Conclusion:Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic xenografts in the distal mouse colon.The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans.This novel model of colon neoplasia has great potential for exploring anatomical differences in colon cancer and testing novel therapeutics.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.51273194,21975246 and 51903233).
文摘Chemotherapeutic and radiation therapy have emerged as two most important treatment strategies to treat cancer in clinical practice;however,to improve anticancer efficacy,combination chemotherapy still remains challenge.Dichloroacetate(DCA)could produce significant cytotoxic effects in certain tumor cells through its distinct mechanism.Radiation therapy with fast neutrons(FNT)has high relative biolgical effectiveness compared to other radiotherapeutics.Herein,we reported the combination chemotherapy with FNT for effective tumor growth inhibition with the assistance of a multilayered nanofiber loading DCA and DCA derivatives.We first synthesized a biodegradable polylysine to condense DCA with negative charge,or to conjugate DCA by condensing synthesis,to obtain Ion-DCA and Co-DCA,respectively.DCA,Ion-DCA or Co-DCA was then loaded into fibers to form multilayer drug-loaded mats.Upon adhesion on the surface of subcutaneous and orthotopic liver tumors,the multilayer drug-loaded mats realized a controllable release of DCA,which reversed the Warburg effect and inhibited cancer cell proliferation.Meantime,irradiation of fast neutrons could seriously damage DNA structure.Combination of the controllable release of DCA and FNT resulted in synergistic cell apoptosis in vitro,and the tumor inhibition in vivo.This study thus provides a new approach to integrate chemotherapy and FNT with the assistance of biocompatible nanofiber for synergistic tumor therapy.
文摘Aim:Strong evidence reveals important differences between cancers in the proximal vs.distal colon.Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several important limitations.We explored whether there were regional differences in the location of murine colon cancers and assessed the utility of murine models to explore the biological basis for such differences.Methods:We re-analyzed data from our previous studies to assess the regional distribution of murine colon cancer.In survival surgery experiments,we injected HT-29 human colon cancer cells into the wall of the cecum or distal colon of Nu(NCr)-Foxn1 nu or NOD.Cg-Prkdc scid Il2rg Tim1Wji/SzJ mice and compared the development of primary tumors and metastases.Results:Within 7-17 weeks after intramural cecal injection of HT-29 cells,eight mice failed to develop solid primary tumors or metastases.In contrast,within four weeks after cell injection into the distal colon,13 mice developed metastases-12 mice developed subcutaneous metastases;of these,four developed liver metastases and one developed both liver and lung metastases.One mouse developed liver metastases only.Histological examination confirmed these lesions were adenocarcinomas.Conclusion:Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic xenografts in the distal mouse colon.The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans.This novel model of colon neoplasia has great potential for exploring anatomical differences in colon cancer and testing novel therapeutics.
