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
脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤...脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。展开更多
The intracellular Fatty Acid Binding Proteins （FABPs） are a well-conserved family which functions as lipid chaperones. Recent findings also reveal that they are crucial mediators of lipid metabolism, cell growth and...The intracellular Fatty Acid Binding Proteins （FABPs） are a well-conserved family which functions as lipid chaperones. Recent findings also reveal that they are crucial mediators of lipid metabolism, cell growth and differentiation, cellular signaling and gene transcription. Ongoing studies are identifying the mechanistic complexity and vast biological diversity of different isoforms of FABPs. This paper introduced the biological function of FABP5 in inflammatory, metabolic diseases and milk fat synthesis.展开更多
目的探讨脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)在宫颈癌组织的表达及其与临床预后的关系.方法行广泛性子宫切除术和系统性腹膜后淋巴结切除术的早期宫颈癌组织蜡块共206例(淋巴结转移阳性41例,阴性165例),另选取相匹配...目的探讨脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)在宫颈癌组织的表达及其与临床预后的关系.方法行广泛性子宫切除术和系统性腹膜后淋巴结切除术的早期宫颈癌组织蜡块共206例(淋巴结转移阳性41例,阴性165例),另选取相匹配年龄的40例因子宫肌瘤行全子宫切除的正常宫颈组织作为空白对照组.采用免疫组化法检测FABP5在206例早期宫颈癌组织标本及正常宫颈组织中的表达;分析FABP5与宫颈癌患者临床、病理参数之间的相关性;采用多变量COX比例风险模型评估FABP5在宫颈癌预后中的价值.结果FABP5高表达主要集中在细胞核和细胞浆中;宫颈癌组织中FABP5的表达较正常宫颈组织显著升高(P<0.05);且在淋巴结转移阳性组较阴性组表达显著升高(P<0.05).而在正常宫颈组织中,FABP5仅在宫颈上皮层低表达;FABP5与FIGO分期(P<0.001)、肿瘤大小(P=0.011)、淋巴结转移(P<0.001)和淋巴脉管浸润(P<0.001)显著相关.多变量COX比例风险模型分析结果显示年龄、盆腔淋巴结转移、肿瘤大小和FABP5为宫颈癌的独立预后因素.生存分析显示FABP5高表达与不良预后显著相关(P<0.05).结论FABP5在宫颈癌中高表达,且可作为宫颈癌不良预后的预测指标.展开更多
Bladder cancer （BC） is the second most common malignancy of the human genitourinary tract,and is characterized by a high recurrence rate and expensive treatment） There is still no ideal biomarker for diagnosing or ...Bladder cancer （BC） is the second most common malignancy of the human genitourinary tract,and is characterized by a high recurrence rate and expensive treatment） There is still no ideal biomarker for diagnosing or monitoring human BC.In the present study,we used proteomics analysis,including two-dimensional fluorescence difference gel electrophoresis （2D DIGE） and matrix-assisted laser desorption ionization time of flight/time of flight mass spectrometry （MALDI-TOF/TOF MS）,to identify new potential protein markers of BC.展开更多
In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal tr...In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state.The detailed route of this signal transduction pathway can be described as follows:when FABP5 expression is increased as the increasing malignancy,excessive amounts of fatty acids from intra-and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ).The phosphorylated or biologically activated PPARγthen modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis.Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice,a seven-fold reduction of tumour incidence,and a 100%reduction of metastasis rate.Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both in vitro and in nude mouse.These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.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.
文摘脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。
文摘The intracellular Fatty Acid Binding Proteins （FABPs） are a well-conserved family which functions as lipid chaperones. Recent findings also reveal that they are crucial mediators of lipid metabolism, cell growth and differentiation, cellular signaling and gene transcription. Ongoing studies are identifying the mechanistic complexity and vast biological diversity of different isoforms of FABPs. This paper introduced the biological function of FABP5 in inflammatory, metabolic diseases and milk fat synthesis.
文摘目的探讨脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)在宫颈癌组织的表达及其与临床预后的关系.方法行广泛性子宫切除术和系统性腹膜后淋巴结切除术的早期宫颈癌组织蜡块共206例(淋巴结转移阳性41例,阴性165例),另选取相匹配年龄的40例因子宫肌瘤行全子宫切除的正常宫颈组织作为空白对照组.采用免疫组化法检测FABP5在206例早期宫颈癌组织标本及正常宫颈组织中的表达;分析FABP5与宫颈癌患者临床、病理参数之间的相关性;采用多变量COX比例风险模型评估FABP5在宫颈癌预后中的价值.结果FABP5高表达主要集中在细胞核和细胞浆中;宫颈癌组织中FABP5的表达较正常宫颈组织显著升高(P<0.05);且在淋巴结转移阳性组较阴性组表达显著升高(P<0.05).而在正常宫颈组织中,FABP5仅在宫颈上皮层低表达;FABP5与FIGO分期(P<0.001)、肿瘤大小(P=0.011)、淋巴结转移(P<0.001)和淋巴脉管浸润(P<0.001)显著相关.多变量COX比例风险模型分析结果显示年龄、盆腔淋巴结转移、肿瘤大小和FABP5为宫颈癌的独立预后因素.生存分析显示FABP5高表达与不良预后显著相关(P<0.05).结论FABP5在宫颈癌中高表达,且可作为宫颈癌不良预后的预测指标.
文摘Bladder cancer （BC） is the second most common malignancy of the human genitourinary tract,and is characterized by a high recurrence rate and expensive treatment） There is still no ideal biomarker for diagnosing or monitoring human BC.In the present study,we used proteomics analysis,including two-dimensional fluorescence difference gel electrophoresis （2D DIGE） and matrix-assisted laser desorption ionization time of flight/time of flight mass spectrometry （MALDI-TOF/TOF MS）,to identify new potential protein markers of BC.
文摘In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state.The detailed route of this signal transduction pathway can be described as follows:when FABP5 expression is increased as the increasing malignancy,excessive amounts of fatty acids from intra-and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ).The phosphorylated or biologically activated PPARγthen modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis.Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice,a seven-fold reduction of tumour incidence,and a 100%reduction of metastasis rate.Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both in vitro and in nude mouse.These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.
