AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined re...AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.展开更多
AIM To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival. METHODS This study examined the expression of TFF1, TFF3 and TWI...AIM To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival. METHODS This study examined the expression of TFF1, TFF3 and TWIST1 in a total of 75 tumor samples, 47 matched normal samples (15 cm from the lesion margin), 30 metastatic lymph nodes, and 10 liver metastatic cancer samples from patients with CRC. The relationship was then analyzed between the protein expression and different clinical records. TFF1, TFF3, TWIST1, E-cadherin, vimentin and beta-catenin mRNA and protein expression levels were measured in colon cancer cell lines with different metastatic potentials (HIEC, HT29, SW620, and LoVo cells), and the correlation of the expression levels with epithelial-mesenchymal transition (EMT) was discussed. RESULTS It was found that 66.7% (50/75), 78.7% (59/75) and 54.7% (41/75) of tumor tissue samples exhibited positive staining for TFF1, TFF3 and TWIST1 and so did 27.3% (13/47), 100% (47/47) and 17% (8/47) of adjacent normal colorectal tissues. Compared with adjacent normal tissues, significant differences were found in the expression of all three proteins in different cancerous tissues (P < 0.05). Higher expression of TFF3 and TWIST1 was significantly correlated with lymph node metastasis (P = 0.034, P = 0.000), advanced stage (P = 0.031, P = 0.003), and poorer survival (P = 0.042 for the TFF3 group, P = 0.003 for the TWIST1 group). The expression of TFF3 and TWIST1 in cancer cell lines was higher than that in HIEC (a normal human intestinal epithelial cell line)(P < 0.05), and the expression intensity demonstrated a tendency to rise with increased metastatic potential both at the protein and mRNA levels. However, TFF1 expression demonstrated the opposite tendency. It was also observed that the expression of E-cadherin and beta-catenin tended to decrease while that of vimentin, TWIST1 and Snail tended to rise with the increase in metastatic potential. CONCLUSION The expression of TFF3 and TWIST1 might be associated with the survival of patients with CRC after curative resection and might be pivotal predictors of disease progression. TFF3 may be correlated to the invasiveness of CRC.展开更多
AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-;...AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies.METHODSSerum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSIONSerum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.展开更多
基金Supported by The Thailand Research Fund through the Royal Golden Jubilee PhD program(grant PHD/0121/2547 code 5LKK/47/B1 to Kosriwong K and Limpaiboon T)Khon Kaen University Research Affairs(grant 48-03-1-01-03)the Centre for Research and Development of Medical Diagnostic Laboratories,Faculty of Associated Medical Sciences(No.06-01), Thailand
文摘AIM:To investigate trefoil factor(TFF) gene copy number,mRNA and protein expression as potential biomarkers in cholangiocarcinoma(CCA).METHODS:TFF mRNA levels,gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction(PCR),quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA,precancerous bile duct dysplasia and from disease-free controls.The functional impact of recombinant human(rh) TFF2 peptide treatment on proliferation and epidermal growth factor receptor(EGFR) /mitogenactivated protein kinase(MAPK) signaling was assessed in the CCA cell line,KMBC,by viable cell counting and immunoblotting,respectively.RESULTS:TFF1,TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls,and was unrelated to gene copy number.TFF1 immunoreactivity was strongly increased in both dysplasia and CCA,whereas TFF2 immunoreactivity was increased only in CCA compared to diseasefree controls.By contrast,TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA.Kaplan-Meier analysis found no association of TFF mRNA,protein and copy number with age,gender,histological subtype,and patient survival time.Treatment of KMBC cells with rhTFF2 stimulated proliferation,triggered phosphorylation of EGFR and downstream extracellular signal related kinase(ERK),whereas co-incubation with the EGFR tyrosine kinase inhibitor,PD153035,blocked rhTFF2-dependent proliferation and EGFR/ERK responses.CONCLUSION:TFF mRNA/protein expression is indicative of CCA tumor progression,but not predictive for histological sub-type or survival time.TFF2 is mitogenic in CCA via EGFR/MAPK activation.
基金the Natural Science Fund of the Xinjiang Uygur Autonomous Region,No.2014211C111
文摘AIM To detect the expression of trefoil factors (TFFs) and TWIST1 in colorectal cancer (CRC) and analyze their correlation with metastasis and survival. METHODS This study examined the expression of TFF1, TFF3 and TWIST1 in a total of 75 tumor samples, 47 matched normal samples (15 cm from the lesion margin), 30 metastatic lymph nodes, and 10 liver metastatic cancer samples from patients with CRC. The relationship was then analyzed between the protein expression and different clinical records. TFF1, TFF3, TWIST1, E-cadherin, vimentin and beta-catenin mRNA and protein expression levels were measured in colon cancer cell lines with different metastatic potentials (HIEC, HT29, SW620, and LoVo cells), and the correlation of the expression levels with epithelial-mesenchymal transition (EMT) was discussed. RESULTS It was found that 66.7% (50/75), 78.7% (59/75) and 54.7% (41/75) of tumor tissue samples exhibited positive staining for TFF1, TFF3 and TWIST1 and so did 27.3% (13/47), 100% (47/47) and 17% (8/47) of adjacent normal colorectal tissues. Compared with adjacent normal tissues, significant differences were found in the expression of all three proteins in different cancerous tissues (P < 0.05). Higher expression of TFF3 and TWIST1 was significantly correlated with lymph node metastasis (P = 0.034, P = 0.000), advanced stage (P = 0.031, P = 0.003), and poorer survival (P = 0.042 for the TFF3 group, P = 0.003 for the TWIST1 group). The expression of TFF3 and TWIST1 in cancer cell lines was higher than that in HIEC (a normal human intestinal epithelial cell line)(P < 0.05), and the expression intensity demonstrated a tendency to rise with increased metastatic potential both at the protein and mRNA levels. However, TFF1 expression demonstrated the opposite tendency. It was also observed that the expression of E-cadherin and beta-catenin tended to decrease while that of vimentin, TWIST1 and Snail tended to rise with the increase in metastatic potential. CONCLUSION The expression of TFF3 and TWIST1 might be associated with the survival of patients with CRC after curative resection and might be pivotal predictors of disease progression. TFF3 may be correlated to the invasiveness of CRC.
基金the Poznan University of Medical Sciences Grant,A helping hand(2014)
文摘AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) antibodies.METHODSSerum TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in CD.CONCLUSIONSerum TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.
