Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, progn...Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.展开更多
BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important r...BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.展开更多
BACKGROUND Papillary thyroid cancer(PTC)often recurs following surgical excision,necessitating reliable long-term screening techniques after initial management.Ultrasound scans have a poor predictive value and biopsy ...BACKGROUND Papillary thyroid cancer(PTC)often recurs following surgical excision,necessitating reliable long-term screening techniques after initial management.Ultrasound scans have a poor predictive value and biopsy and genetic testing have a low sensitivity.Biomarker detection,including thyroglobulin,has reduced accuracy as residual thyroid tissue remains following surgery.Serum/tissue microRNA detection offers a promising alternative to screen for thyroid malignancy.Based on our previous systematic review,miR-146,miR-221 and miR-222 appear most strongly associated with PTC.AIM To perform a systematic review and meta-analysis,evaluating the use of circulating miR-146,miRNA-221 and miR-222 in PTC diagnosis and staging.METHODS A systematic literature search of MEDLINE,Scopus and the EMBASE library was performed.Human participants of any age,sex or geographical distribution were considered.Original studies assessing the diagnostic and prognostic accuracy of circulating serum miRNAs in histologically-confirmed PTC were included.Proportion and regression meta-analyses(logit-transformed)were conducted.PRISMA guidelines were followed throughout the process.RESULTS Among the 1530 studies screened,6 met the inclusion criteria,reporting non-overlapping populations.For the diagnosis of PTC vs benign nodules(BN),the pooled sensitivity of miR-146 was 80.7%(95%CI:65.2%-90.4%),specificity was 66.9%(95%CI:55.5%-76.6%),and false positive rate was 33.1%(95%CI:23.4%-44.5%).Pooled sensitivity,specificity and false positive rate of miR-222 for diagnosis of PTC vs BN was 64.3%(95%CI:50.3%-76.2%),88.8%(95%CI:82.4%-93%)and 11.2%(95%CI:7%-17.6%)respectively.Pooled sensitivity,specificity and false positive rate of miR-221 in this population demonstrated reduced accuracy.Pooled sensitivity and specificity of PTC vs healthy controls for total serum miRNAs were 82%(95%CI:77%-86%)and 84%(95%CI:76%-90%)respectively.The summary area under receiver operating characteristic curve value for the same analysis was 0.89(95%CI:0.86-0.92).CONCLUSION miRNA-146 and miRNA-222 were most sensitive,validating their efficacy in PTC diagnosis.Larger studies are needed for confident population generalisability.Use of two-MRNA types in conjunction needs to be assessed.展开更多
目的探讨冠心病患者血清miRNA-144表达水平与冠状动脉粥样硬化严重程度的相关性。方法选取冠心病患者67例(冠心病组)和同期来医院体检中心进行体检无冠心病体检者30例(对照组),收集基本临床和血生化资料,使用PCR法检测两组样本的血清中m...目的探讨冠心病患者血清miRNA-144表达水平与冠状动脉粥样硬化严重程度的相关性。方法选取冠心病患者67例(冠心病组)和同期来医院体检中心进行体检无冠心病体检者30例(对照组),收集基本临床和血生化资料,使用PCR法检测两组样本的血清中miRNA-144的表达水平,使用Gensini评分法评价冠状动脉病变严重程度,进行单因素和多因素分析。结果冠心病组患者体内血清miRNA-144的表达水平较对照组显著升高(P<0.01),其中急性心肌梗死亚组患者的miRNA-144的表达较对照组变化量最明显。Gensini评分与miRNA-144的表达量呈明显的正相关(r=0.69,P<0.01),受试者工作特征曲线(receiver operating curve,ROC)分析结果显示曲线下面积(area under curve,AUC)为0.9888(P<0.01),灵敏度和特异度分别为98%和98%。结论冠心病患者血清中miRNA-144表达水平升高,且其表达水平与冠状动脉粥样硬化严重程度呈正相关。展开更多
Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a...Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.展开更多
AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polyme...AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.展开更多
文摘Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.
基金Science and Technology Development Foundation(STDF),Project NO.3457(TC/4/Health/2010/hep-1.6)
文摘BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10^(-3) mm^2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10^(-3) mm^2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10^(-3) mm^2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.
文摘BACKGROUND Papillary thyroid cancer(PTC)often recurs following surgical excision,necessitating reliable long-term screening techniques after initial management.Ultrasound scans have a poor predictive value and biopsy and genetic testing have a low sensitivity.Biomarker detection,including thyroglobulin,has reduced accuracy as residual thyroid tissue remains following surgery.Serum/tissue microRNA detection offers a promising alternative to screen for thyroid malignancy.Based on our previous systematic review,miR-146,miR-221 and miR-222 appear most strongly associated with PTC.AIM To perform a systematic review and meta-analysis,evaluating the use of circulating miR-146,miRNA-221 and miR-222 in PTC diagnosis and staging.METHODS A systematic literature search of MEDLINE,Scopus and the EMBASE library was performed.Human participants of any age,sex or geographical distribution were considered.Original studies assessing the diagnostic and prognostic accuracy of circulating serum miRNAs in histologically-confirmed PTC were included.Proportion and regression meta-analyses(logit-transformed)were conducted.PRISMA guidelines were followed throughout the process.RESULTS Among the 1530 studies screened,6 met the inclusion criteria,reporting non-overlapping populations.For the diagnosis of PTC vs benign nodules(BN),the pooled sensitivity of miR-146 was 80.7%(95%CI:65.2%-90.4%),specificity was 66.9%(95%CI:55.5%-76.6%),and false positive rate was 33.1%(95%CI:23.4%-44.5%).Pooled sensitivity,specificity and false positive rate of miR-222 for diagnosis of PTC vs BN was 64.3%(95%CI:50.3%-76.2%),88.8%(95%CI:82.4%-93%)and 11.2%(95%CI:7%-17.6%)respectively.Pooled sensitivity,specificity and false positive rate of miR-221 in this population demonstrated reduced accuracy.Pooled sensitivity and specificity of PTC vs healthy controls for total serum miRNAs were 82%(95%CI:77%-86%)and 84%(95%CI:76%-90%)respectively.The summary area under receiver operating characteristic curve value for the same analysis was 0.89(95%CI:0.86-0.92).CONCLUSION miRNA-146 and miRNA-222 were most sensitive,validating their efficacy in PTC diagnosis.Larger studies are needed for confident population generalisability.Use of two-MRNA types in conjunction needs to be assessed.
文摘目的探讨冠心病患者血清miRNA-144表达水平与冠状动脉粥样硬化严重程度的相关性。方法选取冠心病患者67例(冠心病组)和同期来医院体检中心进行体检无冠心病体检者30例(对照组),收集基本临床和血生化资料,使用PCR法检测两组样本的血清中miRNA-144的表达水平,使用Gensini评分法评价冠状动脉病变严重程度,进行单因素和多因素分析。结果冠心病组患者体内血清miRNA-144的表达水平较对照组显著升高(P<0.01),其中急性心肌梗死亚组患者的miRNA-144的表达较对照组变化量最明显。Gensini评分与miRNA-144的表达量呈明显的正相关(r=0.69,P<0.01),受试者工作特征曲线(receiver operating curve,ROC)分析结果显示曲线下面积(area under curve,AUC)为0.9888(P<0.01),灵敏度和特异度分别为98%和98%。结论冠心病患者血清中miRNA-144表达水平升高,且其表达水平与冠状动脉粥样硬化严重程度呈正相关。
基金Supported by Studies of the authors Mayr C,Pichler M,Neureiter D and Kiesslich T in the research field of this review were supported by research grants of the Jubilaumsfonds derosterreichischen Nationalbank,No.12677 and No.14842the research fund of the Paracelsus Medical University Salzburg,No.08/07/037,No.A-12/02/006-KIE and No.R-16/03/083-MAY
文摘Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.
基金Supported by The University of Mainz Project Grant
文摘AIM： To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis.METHODS： The impact of miR-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（RT-PCR） after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo.RESULTS： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by miR-196a in a dose-dependent andgene-specific manner. High levels of miR-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of miR-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, miR-196a increased thedevelopment of lung metastases in mice after tail veininjection.
