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As one of the most lethal malignancies, pancreatic cancer and its therapy remains a big problem all around the world. With the few candidates for surgery and the poor outcome for chemotherapy, the immunotherapy becomes one important direction. Mesothelin, a membrane protein, expresses at low levels in normal tissues, but is re-expressed at a high frequency in pancreatic cancer, which makes mesothelin an ideal target for immunotherapy.This review summarizes the progression of mesothein-targeted immunotherapy for pancreatic cancer.
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As one of the most lethal malignancies, pancreatic cancer and its therapy remains a big prob-lem all around the world. With the few candidates for surgery and the poor outcome for chemotherapy, the im-munotherapy becomes one important direction. Mesothelin, a membrane protein, expresses at low levels in normal tissues, but is re-expressed at a high frequency in pancreatic cancer, which makes mesothelin an ideal target for im-munotherapy.This review summarizes the progression of mesothein-targeted immunotherapy for pancreatic cancer.
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Purpose To analyze the Wnt/β-catenin signaling pathway related TCF/LEF binding sites in human mesothelin gene and to identify the core promoter region of the gene in the ovarian cancer cells. Methods The possible TCF/LEF transcription factor binding sites in the promoter region of human meosothelin gene were analyzed by bioinformatics method. The 1764 bp promoter sequence near the 5'end of the human mesothelin gene were cloned. The fragments was truncated differently at the 5' end and cloned into p GL3-basic report gene vector and transfected into human ovarian cancer cell lines SKOV-3 and 3-AO. The activity of diffetent promoter fragmentis was detected by double luciferase reporter gene system. Results There were multiple potential TCF/LEF binding sites in the promoter region of the human mesothelin gene. Three fragments of mesothelin gene promoter region-1456-+ 308、-164-+ 308、+ 47-+ 308 were cloned and amplified successfully, the p GL3 vector was constructed by sequencing. After transfection of SKOV-3 and 3-AO cells, the double luciferase reporter gene system showed that the-1456-+ 308 fragments and-164-+ 308 framents had high promoting activity in both cell lines, and the activity of + 47-+308 fragments was significantly lower than that of the former two cell lines (P<0.01). Conclusion The-164-+ 47 sequence containing TCF/LEF transcription factor binding site is the core promoter region of mesothelin gene in ovarian cancer, which lays a foundation for further study on the regulation mechanism of mesothelin gene expression in ovarian cancer.
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Objective To investigate the different expression of preoperative serum mesothelin level in colon cancer patients.Methods One hundred and twenty five patients who were first diagnosed with colon cancer (a scase group) and 75 healthy subjects (a scontrol group) were enrolled in the Fourth People's Hospital of Yulin from Mar.2014 to Jun.2016.The serum levels of mesothelin both in the preoperative case group and control group were detected by enzyme linked immunosorbent assay.Diagnostic value of mesothelin in colon cancer was evaluated by receiver operating characteristic curve.The survival data of both goups were analyzed by Kaplan-Meier and Logrank test.Results Serum endothelin level in the control group was significantly lower than those in the case group [(0.91 ± 0.80) pg/ml and (7.63 ± 3.25) pg/ml,repectively,t =17.57,P ＜ 0.001].There were significant differences in the serum level of endothelin varied significantly in case group with tumor size,TNM stage,invasion,lymph node metastasis and distal metastasis (P ＜ 0.05).The best preoperative diagnostic value for serum levels of colon cancer was 2.36 pg/ml,and the best preoperative diagnostic value was 8.62 pg/ml for predicting the progression of colon cancer.One hundred and twenty-five cases of colon cancer were divided into low serum mesothelin group (n =56,the level of mesothelin ≤ 8.62 pg/ml) and high serum mesothelin group (n =69,the level of mesothelin ＞ 8.62 pg/ml).The difference of survival between the two groups was statistically significant (t =36.01,P ＜ 0.001).Conclusion Serum mesothelin may serve as a potential biomarker for the diagnosis of colon cancer and its progression.
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Objective To investigate the different expression of preoperative serum mesothelin level in colon cancer patients.Methods One hundred and twenty five patients who were first diagnosed with colon cancer (a scase group) and 75 healthy subjects (a scontrol group) were enrolled in the Fourth People's Hospital of Yulin from Mar.2014 to Jun.2016.The serum levels of mesothelin both in the preoperative case group and control group were detected by enzyme linked immunosorbent assay.Diagnostic value of mesothelin in colon cancer was evaluated by receiver operating characteristic curve.The survival data of both goups were analyzed by Kaplan-Meier and Logrank test.Results Serum endothelin level in the control group was significantly lower than those in the case group [(0.91 ± 0.80) pg/ml and (7.63 ± 3.25) pg/ml,repectively,t =17.57,P ＜ 0.001].There were significant differences in the serum level of endothelin varied significantly in case group with tumor size,TNM stage,invasion,lymph node metastasis and distal metastasis (P ＜ 0.05).The best preoperative diagnostic value for serum levels of colon cancer was 2.36 pg/ml,and the best preoperative diagnostic value was 8.62 pg/ml for predicting the progression of colon cancer.One hundred and twenty-five cases of colon cancer were divided into low serum mesothelin group (n =56,the level of mesothelin ≤ 8.62 pg/ml) and high serum mesothelin group (n =69,the level of mesothelin ＞ 8.62 pg/ml).The difference of survival between the two groups was statistically significant (t =36.01,P ＜ 0.001).Conclusion Serum mesothelin may serve as a potential biomarker for the diagnosis of colon cancer and its progression.
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BACKGROUND: Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis. METHODS: We evaluated calretinin, WT1, and mesothelin expression by immunohistochemical staining in 117 gastric adenocarcinomas. RESULTS: Mesothelin was positively stained in 30 cases (25.6%). Mesothelin expression was related to increased depth of invasion (p = .002), lymph node metastasis (p = .013), and presence of lymphovascular (p = .015) and perineural invasion (p = .004). Patients with mesothelin expression had significantly worse disease-free survival rate compared with that of nonmesothelin expression group (p = .024). Univariate analysis showed that mesothelin expression is related to short-term survival. None of the 117 gastric adenocarcinomas stained for calretinin or WT1. CONCLUSIONS: Mesothelin expression was associated with poor prognosis. Our results suggest that mesothelin-targeted therapy should be considered as an important therapeutic alternative for gastric adenocarcinoma patients with mesothelin expression.
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Objective To explore the clinical significance of expression of soluble mesothelin relatedprotein(SMRP)and carbo-hydrate antigen (CA125)in the serum and tumor tissues of the patients with ovarian cancer.Methods The preoperative and post-operative levels of SMRP and CA125 in serum and ovarian cancer tissues were detected in 82 patients with ovarian cancer (group A),76 cases of benign ovarian tumor (group B)and 53 healthy women (group C)by using ELISA and the immunohistochemical method respectively.Serum levels of SMRP and CA125 in the ovarian cancer patients were measured after one year by ELISA.The correlation among the various statistical indexes was analyzed.Results The positive expression rates of SMRP and CA125 in the group A were significantly higher than those in the group B(P <0.05);compared with the group B and C,the preoperative serum level of CA125 and SMRP in the group A was significantly increased (P <0.001);the preoperative serum CA 125 level in the group B was higher than that in the group C;compared with the stage Ⅰ and Ⅱ,the serum CA125 and SMRP in the stage Ⅲ and Ⅳ of o-varian cancer were significantly increased(P <0.05 );compared with before operation,the postoperative SMRP and CA125 levels were significantly decreased(P <0.05).After 1 year of discharge from hospital,compared with the basically stable patients,serum CA125 and SMRP levels in the patients with ovarian cancer recurrence were significantly increased(P <0.05).The sensitivity and specificity for diagnosing ovarian cancer,any single detection was inferior to the combination detection of CA125 and SMRP.Conclu-sion The combination detection of CA125 and SMRP has an important value for increasing the sensitivity and specificity of ovarian cancer diagnosis,early diagnosis,illness condition monitoring and effect evaluation.
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Objective To observe the targeted function of a mesothelin antibody modified nanoprobe in human pancreatic cancer BxPC3 cell.Methods The Fe3O4@SiO2 nanoprobe was prepared by St(o)ber method,and then quantum dots (CdTe) and mesothelin antibody was crosslinked to obtain the properties of targeting and fluorescent.Fluorescent nano Fe3O4@SiO2 probes and BxPC3 cells were incubated in vitro for 30 min.Its targeting performance was tested by the CCD imaging system and magnetic separation technology.HepG-2 and K562 cells with low expression of mesothelin were selected as reference cells.Results This preparation method of nanoprobe could produce a uniform and narrow distribution particle with particle size mainly ranging from 120 to 140 nm.The cell adsorption experiments showed that the adsorption efficiency of BxPC3,HepG-2 and K562 by nanoprobe without crosslinking antibody were less than 20％,as a non-specific adsorption; and the adsorption efficiency of BxPC3,HepG-2 and K562 by crosslinking mesothelin antibody nanoprobe were (53.9 ± 1.8) ％,(8.0 ± 2.1) ％ and (8.9 ± 2.3) ％ respectively,and the adsorption capacity with BxPC3 was significantly increased.Conclusions The nanoprobe modified by mesothelin antibody can effectively recognize BxPC3 cells which highly expressing mesothelin.
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Objective To evaluate the values of combined detection of carbohydrate antigen 125(CA125) ,human epididymis gene protein 4(HE4) ,soluble mesothelin related peptides(SMRP) in early diagnosis for ovarian cancer and the high-risk factors of ovari-an cancer .Methods 43 patients with malignant ovarian cancer were served as the malignant group ,54 patients with benign ovarian tumors as the benign group ,45 healthy women as the control group .Roche Cobas 6000 Automatic Electrochemiluminescence Immu-noassay Analyzer and enzyme-linked immunosorbent assay (ELISA) were adopted to detect serum CA125 ,HE4 ,SMRP levels . High-risk factors of ovarian cancer was subject to Logistic regression analysis .Results Serum levels of CA125 ,HE4 and SMRP of patients in malignant group were significantly higher than those in the benign group and the control group (P<0 .01) .The sensitivi-ties of CA125 ,HE4 and SMRP detection alone for ovarian cancer diagnosis were 73 .3% ,82 .8% and 70 .8% ,respectively ,while their specificities were 79 .1% ,87 .4% and 83 .3% ,respectively .The sensitivity and specificity of joint detection of CA 125 ,HE4 , SMRP for ovarian cancer diagnosis were 90 .2% and 79 .3% ,respectively .Logistic regression analysis showed that age at menarche younger than 13 years ,menstrual cycle less than 30 d and irregular menstruation were the high-risk factors of ovarian cancer ,with their odds ratio(OR) of 2 .11[95% confidence interval(CI):1 .09-4 .10 ,1 .91(95% CI:1 .21-3 .10) and 1 .57(95% CI:0 .83-2 .94) .Conclusion CA125 detection combined with HE4 or SMRP can markedly improve the diagnostic sensitivity for ovarian cancer .
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Tumor markers for early diagnosis of cancer is an important auxiliary mean,which for early tumor detection,monitoring and for judging curative effect of treatment regimens play important role.Clinical method for early diagnosis on ovarian cancer is the detection of serum CA125,however,its precision and specificity for early diagnosis are not enough.It has been found that in the development period of the patients with ovarian cancer,SMRP and CA125 is co-expression.This article reviews the value of serum mesothelin on diagnosis of epithelial ovarian cancer to provide reference on early diagnosis and treatment.
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Introduction: Malignant Pleural Mesothelioma (MPM) is a tumor of the mesothelial cells related to asbestos exposure. This malignancy is extremely aggressive, with poor response to different treatment modalities, and it has a mean survival of 8 months since diagnosis. With the introduction of new chemotherapeutic agents and trimodality protocols, five-year survival of 40 percent in initial stages has been reported. Serum detection of Soluble Mesothelin-related Protein (SMRP) could be used for screening of MPM. Using the MESOMARK® test, 53 percent of MPM patients had levels greater than 1,5 nM, while 99 percent of control patients had lower concentrations. The aim of this study is to evaluate the use of this test in Chile and determine its utility for screening ofMPM. Methods: Quantitative blind measurement of serum SMRP by MESOMARK® test. We studied 3 groups: 8 workers exposed to asbestos, 5 patients with diagnosed MPM and 14 age matched workers without known exposure to asbestos. Participants were informed of the study. Results: Mean +/- standard deviation SMRP levels in the control group was 0,53 +/- 0,4 nM, 0,89 +/- 0,46 nM in patients exposed to asbestos and 10,68 +/- 10,28 nM in MPMpatients. Differences between the groups were statistically significant (p = 0,02). In the MPM group, 3 patients were found to have SMRP levels greater than 1,5 nM (17,27 nM; SD 6,95) and 2 patients normal values (0,79 nM; SD 0,32). Using a cut-off value of 1,5 nM, sensitivity of the test was 60 percent and specificity was 100 percent. Conclusions: Detection of SMRP levels allowed to identify patients with MPM, three of whom had very high concentrations. The sensitivity and specificity found is similar to that previously reported. If our results are confirmed in greater studies, SMRP detection could be used for screening of MPM.
Resumen Introducción: El Mesotelioma Maligno (MM) es un tumor de las células mesoteliales relacionado a la exposición a asbesto, altamente agresivo, con pobre respuesta al tratamiento y con una sobrevida promedio de 8 meses después del diagnóstico. Sin embargo, nuevos agentes quimioterapéuticos y protocolos de terapia trimodal han logrado sobrevidas de hasta 40 por ciento en etapas iniciales. La detección en sangre periférica de Péptidos Solubles Relacionados a Mesotelina (SMRP) podría ser útil para el diagnóstico precoz de MM. Utilizando el test MESOMARK® para la determinación de SMRP, 53 por ciento de los pacientes con MM tenían valores mayores a 1,5 nM mientras que 99 por ciento de los controles mostraron valores inferiores. El objetivo del presente trabajo es evaluar la implementación de este test en Chile y determinar su utilidad para el diagnóstico precoz en MM. Métodos: Medición cuantitativa de SMRP en suero humano por test MESOMARK®. Se realizaron mediciones en forma ciega a 8 trabajadores con exposición a asbesto, a 5 pacientes con MMy a 14 voluntarios sin exposición. Todos los participantes fueron informados del estudio. Resultados: El promedio +/- desviación estándar de SMRP en el grupo control fue de 0,53 +/- 0,4 nM, de 0,89 +/- 0,46 nM en los expuestos sin MMy de 10,68 +/- 10,28 nM en el grupo con MM; encontrándose una diferencia estadísticamente significativa entre los valores de estos tres grupos (p = 0,02). En el grupo con MM, 3 pacientes tuvieron concentraciones mucho mayores a 1,5 nM (17,27 nM; DS 6,95) y 2 valores normales (0,79 nM; DS 0,32). Utilizando un valor de 1,5 nM como punto de corte, la sensibilidad fue de 60 por ciento y la especificidad de 100 por ciento. Conclusiones: La medición de SMRP permitió diferenciar a los pacientes con MM, presentando 3 de ellos concentraciones muy elevadas. La sensibilidad y especificidad encontrada es similar con datos previamente reportados. De confirmarse estos resultados en estudios con mayor ...
Subject(s)
Middle Aged , Biomarkers, Tumor/blood , Mesothelioma/diagnosis , Mesothelioma/blood , Pleural Neoplasms/diagnosis , Pleural Neoplasms/blood , GPI-Linked Proteins/blood , Air Pollutants, Occupational , Asbestos/adverse effects , Early Diagnosis , Environmental Exposure , Membrane Glycoproteins/blood , ROC Curve , Sensitivity and Specificity , Time Factors , Mass Screening/methodsABSTRACT
Objective To compare the mesothelin expressions in 3 human pancreatic cancer cell lines between in vitro and in vivo and the developing speed among the subcutaneous tumors implanted with the 3 human pancreatic cancer cell lines in nude mice.Methods The human pancreatic cancer cell lines ( SW1990,BxPC3 and PANC1 ) were cultured and then were implanted subcutaneously into left axillas of nude mice.The volumes of these subcutaneous tumors were recorded every week to estimate their developing speed.The mice implanted with SW1990 and BxPC3 cells were observed for three weeks,while the mice implanted with PANC1 cell were observed for five weeks.The Western blot method was used to measure the expressions of mesothelin in the 3 kinds of cells and subcutaneous tumors,while immunohistochemical staining was applied to determine the expressions of mesothelin in 3 kinds of subcutaneous tumors.Results The sequence of quantities of expressions of mesothelin in these cell lines in vitro were BxPC3 ＞ PANC1 ＞ SW1990,and the sequence of quantities of expressions in vivo were SW1990 ＞ BxPC3 ＞ PANC1.One handrued percent of the tumors grew out successfully,and the sequence of speeds of their growth was SW1990 ＞ BxPC3 ＞ PANC1.Conclusions The mesothelin expressions among 3 kinds of pancreatic cancer cell line are different.The developing speeds of tumors originated from different subcutaneous tumors in nude mice are also different,and there is no association between them.
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Objective:To study the influence of silencing mesothelin(MSLN) gene on the proliferation of ovarian cancer cell line SKOV3 in vitro the growth of human ovarian xenograft in nude mice in vivo.Methods:MSLN-silenced cells (SKOV3-MSLN-shRNA ) and control cells (SKOV3-MSLN-neg) were established after being infected with RNA interference lentivirus and empty vector lentivirus, respectively. SKOV3 cells were used as blank control. Cell proliferation was assayed by clone formation test and cell counting assay. The xenografted model of the three cell lines were established in nude mice. After 2 weeks, the nude mice were sacrificed, and the tumor formation rate, tumor weight, tumor number, and tumor position were recorded. Results:The ability of proliferation of SKOV3-MSLN-shRNA cells was obviously decreased compared with SKOV3-MSLN-neg cells and SKOV3 cells in vitro. The difference was significant (P0.05). The average tumor weight, tumor number, and number of tumor position were all decreased in SKOV3-MSLN-shRNA group compared with the two control groups (P<0.05). Conclusion:Silencing MSLN gene decreased the proliferation of ovarian cancer SKOV3 cells in vitro and inhibited the growth of xenografts of ovarian cancer cells in nude mice.
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Objective To investigate the function of mesothelin by analyzing the location,the expressions and the adhesive ability of mesothelin and CA125 in human epithelial ovarian cancer.Methods Mesothelin and CA125 protein expressions and locations in human epithelial ovarian cancer tissues and cell lines were determined by indirect immunofluorescence double maker and Western blot.Cell adhesive ability was detected by EDTA-induced cell detachment.Results Mesothelin and CA125 were specifically located in cytomembrane of human epithelial ovarian cancer cells.Expressions of mesothelin in the SKOV-3 and 3AO cells were weaker than those in the OVCAR-3.SKOV-3 and 3AO cells adhered less effectively to plastic substance and matrigel than OVCAR-3(P
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Objective:To construct a recombinant lentivirus plasmid of RNA interference targeting (MSLN) gene and to observe its effect on MSLN expression in human ovarian cancer cell line OVCAR-3 and its effect on cell proliferation. Methods: According to the Genbank information of MSLN, four RNA interfering sequences and a negative sequence were designed and inserted into plasmid pRNAT-U6.2/Lenti and 5 kinds of plasmids were packaged: LV-MSLN-negative,LV-MSLN-shRNA1, LV-MSLN-shRNA2, LV-MSLN-shRNA3, and LV-MSLN-shRNA4; and they were used to transfect OVCAR-3 cells. Western blotting and indirect immunofluorescence were then used to investigate the interfering efficiency. The plasmid with high interfering efficiency was packaged. The cell proliferation test and clone-forming test was used to assess the changes in cell proliferation. Results: DNA sequencing showed that the sequences of 5 recombinant lentivirus plasmids were correct. Lentivirus packaging was successfully done. Western blotting analysis confirmed that LV-MSLN-shRNA4 had the highest interfering efficiency (90%). MSLN specifically bound to cytomembrane of OVCAR-3 cells. Expression of MSLN in the interfered cells (OVC-shRNA) was weaker than that in the control cells (OVC-neg,OVC). OVC-shRNA cells([11.2?1.3]?105) grew slowly compared to OVC-neg cells([20.5?2.5]?105) and OVC cells([21.9?2.3]?105) (P