Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment ...Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.展开更多
AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array compar...AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.展开更多
基金supported by the National Natural Science Foundation of China(82072025,82072026,82102162,and 82303886)the“Leading Goose”Research and Development Program of Zhejiang Province(2023C03062)+1 种基金the National Natural Science Foundation of Zhejiang Province(LY22H160040 and LQ22H180010)the Key Research and Development Project of Lishui City(2022ZDYF12,2022ZDYF20,and 2022ZDYF20).
文摘Background:Radiofrequency ablation(RFA)is an efficient treatment with unlimited potential for liver cancer that can effectively reduce patient mortality.Understanding the biological process related with RFA treatment is important for improving treatment strategy.This study aimed to identify the critical targets for regulating the efficacy of RFA.Methods:The RFA treatment in hepatocellular carcinoma(HCC)tumor models in vivo,was analyzed by RNA sequencing technology.The heat treatment in vitro for HCC tumor cells was also constructed to explore the mechanism after RFA treatment in tumor cells.Nanoparticles with high affinity to tumor cells were applied as a new therapy to interfere with the expression of maternal embryonic leucine zipper kinase(MELK).Results:It was found that RFA treatment upregulated MELK expression,and MELK inhibition promoted RFA efficacy by immunogenic cell death and the antitumor response,including anti-tumoral macrophage polarization and increased CD8+T cell cytotoxicity in HCC.Mechanically,MELK binds to fatty acid-binding protein 5(FABP5),and affects its ubiquitination through the K48R pathway to increase its stability,thereby activating protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling axis to weaken the RFA-mediated antitumor effect.In addition,the synthesis of arginylglycylaspartic acid(RGD)-lipid nanoparticles(LNPs)targeting tumor cell-intrinsic MELK enhanced RFA efficacy in HCC.Conclusions:MELK is a therapeutic target by regulating RFA efficacy in HCC,and targeting MELK via RGD-LNPs provides new insight into improving RFA efficacy in HCC clinical treatment and combating the malignant progression of liver cancer.
基金Supported by Fundacao de AmparoàPesquisa do Estado de Sao Paulo-FAPESP,No.2009/07145-9
文摘AIM To identify common copy number alterations on gastric cancer cell lines.METHODS Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis.RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11RA) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 RA and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.
