Mesothelin,C-ERC/mesothelin is a 40-kD a cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura,peritoneum,and pericardium.Moreover,mesothelin has been shown to be overexpress...Mesothelin,C-ERC/mesothelin is a 40-kD a cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura,peritoneum,and pericardium.Moreover,mesothelin has been shown to be overexpressed in several human cancers,including virtually all mesothelioma and pancreatic cancer approximately 70% of ovarian cancer and extra bile duc cancer,and 50% of lung adenocarcinomas and gastric cancer.The full-length human mesothelin gene encodes the primary product,a 71-k Da precursor protein.The71-kD a mesothelin precursor is cleaved into two products40-k Da C-terminal fragment that remains membranebound via glycosylphosphatidylinositol anchor,and a31-kD a N-terminal fragment,megakaryocyte potentiating factor,which is secreted into the blood.The biologica functions of mesothelin remain largely unknown However,results of recent studies have suggested tha the mesothelin may play a role of cell proliferation and migration.In pancreatic cancer,mesothelin expression was immunohistochemically observed in all cases,bu absent in normal pancreas and in chronic pancreatitis Furthermore,the expression of mesothelin was correlated with an poorer patient outcome in severa human cancers.The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy.The present review discusses the expression and function o mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.展开更多
AIM:To investigate the effect of mesothelin in the remodeling of the endocrine pancreas in neonatal rats.sothelin expression in INS-1 cells was carried out to investigate the effect of mesothelin during cell prolifera...AIM:To investigate the effect of mesothelin in the remodeling of the endocrine pancreas in neonatal rats.sothelin expression in INS-1 cells was carried out to investigate the effect of mesothelin during cell proliferation and cell apoptosis in vitro.Adenovirus-mediated RNA interference was performed to block mesothelin in vivo to directly assess the role of mesothelin in the remodeling of the endocrine pancreas in neonatal rats.RESULTS:Exogenous overexpression of mesothelin promoted cell proliferation,cell colony formation and enhanced cell resistance to apoptosis of INS-1 cells.Down-regulation of mesothelin made no difference in cell proliferation and apoptosis compared with that in the control group.After an injection of adenovirusmesothelin,a significantly increased number of small islets appeared,and the expression of PCNA was decreased on day 7 and day 14 compared with the AdEGFP group.CONCLUSION:Mesothelin was able to promoteβcell proliferation in the remodeling stage of neonatal rats.Mesothelin may have an important role in the remodeling of the endocrine pancreas in neonatal rats.展开更多
Objective: To study the correlation of serum mesothelin and human epididymis secretory protein 4 contents with cellular infiltrative growth in patients with ovarian cancer. Methods:Patients with ovarian cancer who und...Objective: To study the correlation of serum mesothelin and human epididymis secretory protein 4 contents with cellular infiltrative growth in patients with ovarian cancer. Methods:Patients with ovarian cancer who underwent surgical resection in West Coast Medical Center of the Affiliated Hospital of Qingdao University between June 2013 and December 2016 were selected as the ovarian cancer group of the study, and healthy women who received physical examination in China University of Petroleum (East China) Hospital during the same period were selected as the control group of the study. Serum was collected from two groups of subjects to detect serum mesothelin and human epididymis secretory protein 4 contents, and the ovarian cancer lesions and adjacent lesions were collected from ovarian cancer group to detect the expression of proliferation, apoptosis and invasion genes. Results: Serum mesothelin and human epididymis secretory protein 4 contents of ovarian cancer group were significantly higher than those of control group;FUNDC1, LSD1, TNFAIP8, CXCR4, β-catenin, CD44, PELP1, Slug, ZEB1 and Snail mRNA expression in ovarian cancer lesions were significantly higher than those in adjacent lesions and positively correlated with serum mesothelin and human epididymis secretory protein 4 contents while MFN2, PTEN, FN14 and E-cadherin mRNA expression were significantly lower than those in adjacent lesions and negatively correlated with serum mesothelin and human epididymis secretory protein 4 contents. Conclusion: Serum mesothelin and human epididymis secretory protein 4 contents abnormally increase in patients with ovarian cancer and are associated with the infiltrative growth of cancer cells.展开更多
The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic aci...The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic acid complex nanocapsules(HFe-TA)may effectively degrade and release Fe^(2+) ions,Fe^(2+)ions induce the production of·OH,however,the fenton reaction needs amount of H_(2)O_(2)to enhance chemodynamic therapy.Due to their deficiencies,such nanoparticles cannot realize intravenous drug delivery.Here,the mesothelin-targeted membrane(MTM)was constructed to realize accurate delivery nano-system,mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM.Lactate oxidase(Lox)was loaded on HFe-TA to obtain Lox@HFe-TA.Lox@HFe-TA was coated with MTM to develop the MTM nanosystem.Tirapazamine(TPZ)therapy also requires hypoxia circumstance.The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro.We also tested the biological safety of the treatment.In this study,we overcame the EPR defects via the MTM nanosystem,which can realize acute targeted delivery to the tumour site,lactate depletion,promoted reactive oxygen species(ROS)induction,enhanced the effect of TPZ,demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.展开更多
文摘Mesothelin,C-ERC/mesothelin is a 40-kD a cell surface glycoprotein that is normally present on normal mesothelial cells lining the pleura,peritoneum,and pericardium.Moreover,mesothelin has been shown to be overexpressed in several human cancers,including virtually all mesothelioma and pancreatic cancer approximately 70% of ovarian cancer and extra bile duc cancer,and 50% of lung adenocarcinomas and gastric cancer.The full-length human mesothelin gene encodes the primary product,a 71-k Da precursor protein.The71-kD a mesothelin precursor is cleaved into two products40-k Da C-terminal fragment that remains membranebound via glycosylphosphatidylinositol anchor,and a31-kD a N-terminal fragment,megakaryocyte potentiating factor,which is secreted into the blood.The biologica functions of mesothelin remain largely unknown However,results of recent studies have suggested tha the mesothelin may play a role of cell proliferation and migration.In pancreatic cancer,mesothelin expression was immunohistochemically observed in all cases,bu absent in normal pancreas and in chronic pancreatitis Furthermore,the expression of mesothelin was correlated with an poorer patient outcome in severa human cancers.The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy.The present review discusses the expression and function o mesothelin in cancer cells and the utility of mesothelin as a target of cancer therapy.
基金Supported by National Natural Science Foundation of China,No.81070620 and No.81170715Jiangsu Province’s Universities Natural Science Research,No.09KJB320009
文摘AIM:To investigate the effect of mesothelin in the remodeling of the endocrine pancreas in neonatal rats.sothelin expression in INS-1 cells was carried out to investigate the effect of mesothelin during cell proliferation and cell apoptosis in vitro.Adenovirus-mediated RNA interference was performed to block mesothelin in vivo to directly assess the role of mesothelin in the remodeling of the endocrine pancreas in neonatal rats.RESULTS:Exogenous overexpression of mesothelin promoted cell proliferation,cell colony formation and enhanced cell resistance to apoptosis of INS-1 cells.Down-regulation of mesothelin made no difference in cell proliferation and apoptosis compared with that in the control group.After an injection of adenovirusmesothelin,a significantly increased number of small islets appeared,and the expression of PCNA was decreased on day 7 and day 14 compared with the AdEGFP group.CONCLUSION:Mesothelin was able to promoteβcell proliferation in the remodeling stage of neonatal rats.Mesothelin may have an important role in the remodeling of the endocrine pancreas in neonatal rats.
文摘Objective: To study the correlation of serum mesothelin and human epididymis secretory protein 4 contents with cellular infiltrative growth in patients with ovarian cancer. Methods:Patients with ovarian cancer who underwent surgical resection in West Coast Medical Center of the Affiliated Hospital of Qingdao University between June 2013 and December 2016 were selected as the ovarian cancer group of the study, and healthy women who received physical examination in China University of Petroleum (East China) Hospital during the same period were selected as the control group of the study. Serum was collected from two groups of subjects to detect serum mesothelin and human epididymis secretory protein 4 contents, and the ovarian cancer lesions and adjacent lesions were collected from ovarian cancer group to detect the expression of proliferation, apoptosis and invasion genes. Results: Serum mesothelin and human epididymis secretory protein 4 contents of ovarian cancer group were significantly higher than those of control group;FUNDC1, LSD1, TNFAIP8, CXCR4, β-catenin, CD44, PELP1, Slug, ZEB1 and Snail mRNA expression in ovarian cancer lesions were significantly higher than those in adjacent lesions and positively correlated with serum mesothelin and human epididymis secretory protein 4 contents while MFN2, PTEN, FN14 and E-cadherin mRNA expression were significantly lower than those in adjacent lesions and negatively correlated with serum mesothelin and human epididymis secretory protein 4 contents. Conclusion: Serum mesothelin and human epididymis secretory protein 4 contents abnormally increase in patients with ovarian cancer and are associated with the infiltrative growth of cancer cells.
基金the mission book of promotion program of basic and clinical collaborative research of Anhui Medical University(No.2022xkjT028)Anhui Provincial Scientific Research Preparation Plan Project(No.2022AH051171)+6 种基金the Anhui Provincial Natural Science Foundation(No.2208085MH240)Postgraduates of Colleges and Universities in Anhui Province(No.YJS20210308)the National Natural Science Foundation of China(No.81602425)the Anhui Quality Engineering Project(Nos.2020jyxm0898,2020jyxm0910,and 2019kfkc334)the Anhui Medical University Clinical Research Project(No.2020xkj176)the Anhui Health Soft Science Research Project(No.2020WR01003)the Key Research and Development Program of Anhui Province(No.201904a07020045).
文摘The enhanced permeability and retention(EPR)effect alone is not enough for nanoparticles to reach the target.Combination of active and passive targeting may be an effective drug delivery route.Hollow ferric-tannic acid complex nanocapsules(HFe-TA)may effectively degrade and release Fe^(2+) ions,Fe^(2+)ions induce the production of·OH,however,the fenton reaction needs amount of H_(2)O_(2)to enhance chemodynamic therapy.Due to their deficiencies,such nanoparticles cannot realize intravenous drug delivery.Here,the mesothelin-targeted membrane(MTM)was constructed to realize accurate delivery nano-system,mesothelin antibody was expressed on the 293T cell membrane to prepare a MTM.Lactate oxidase(Lox)was loaded on HFe-TA to obtain Lox@HFe-TA.Lox@HFe-TA was coated with MTM to develop the MTM nanosystem.Tirapazamine(TPZ)therapy also requires hypoxia circumstance.The MTM nanosystem combined with TPZ can significantly kill tumour cells and inhibit metastasis in vivo and in vitro.We also tested the biological safety of the treatment.In this study,we overcame the EPR defects via the MTM nanosystem,which can realize acute targeted delivery to the tumour site,lactate depletion,promoted reactive oxygen species(ROS)induction,enhanced the effect of TPZ,demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.
