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
Cancer remains the second leading cause of death worldwide and a major public health and economic issue.To reduce the burden,new approaches are necessary to diagnose the disease at early stages and improve clinical ou...Cancer remains the second leading cause of death worldwide and a major public health and economic issue.To reduce the burden,new approaches are necessary to diagnose the disease at early stages and improve clinical outcomes of cancer patients,for which understanding the molecular mechanisms of carcinogenesis is crucial.Autophagy is a pro-survival pathway that ensures the removal and renewal of cellular macromolecular structures,thus playing a crucial role in the maintenance of cellular homeostasis.Dysregulation of autophagy can favor chemoresistance and survival of dormant cancer cells,thus favoring cancer progression and relapse.Several studies report dysregulated expression of long non-coding RNAs and micro-RNAs acting as tumor suppressors or tumor promoters by targeting genes involved in the autophagy pathway.Here,we focus on the role played by non-coding RNAs-mediated regulation of autophagy in development and progression of cancers in women.Understanding how epigenetics can impact autophagy might open novel therapeutic strategies in the fight against cancers in women.展开更多
Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination....Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.展开更多
Hepatocellular carcinoma(HCC) is the leading primary liver cancer and its clinical outcome is still poor. MicroRNAs(mi RNAs) have demonstrated an interesting potential to regulate gene expression at post-transcription...Hepatocellular carcinoma(HCC) is the leading primary liver cancer and its clinical outcome is still poor. MicroRNAs(mi RNAs) have demonstrated an interesting potential to regulate gene expression at post-transcriptional level. Current findings suggest that mi RNAs deregulation in cancer is caused by genetic and/or epigenetic, transcriptional and post-transcriptional modifications resulting in abnormal expression and hallmarks of malignant transformation: aberrant cell growth, cell death, differentiation, angiogenesis, invasion and metástasis. The important role of mi RNAs in the development and progression of HCC has increased the efforts to understand and develop mechanisms of control overt this single-stranded RNAs. Several studies have analyzed tumoral response to the regulation and control of deregulated mi RNAs with good results in vitro and in vivo, proving that targeting aberrant expression of mi RNAs is a powerful anticancer therapeutic. Identification of up and/or down regulated mi RNAs related to HCC has led to the discovery of new potential application for detection of their presence in the affected organism. Mi RNAs represent a relevant new target for diagnosis, prognosis and treatment in a wide variety of pathologic entities, including HCC. This manuscript intends to summarize current knowledge regarding mi RNAs and their role in HCC development.展开更多
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.
文摘Cancer remains the second leading cause of death worldwide and a major public health and economic issue.To reduce the burden,new approaches are necessary to diagnose the disease at early stages and improve clinical outcomes of cancer patients,for which understanding the molecular mechanisms of carcinogenesis is crucial.Autophagy is a pro-survival pathway that ensures the removal and renewal of cellular macromolecular structures,thus playing a crucial role in the maintenance of cellular homeostasis.Dysregulation of autophagy can favor chemoresistance and survival of dormant cancer cells,thus favoring cancer progression and relapse.Several studies report dysregulated expression of long non-coding RNAs and micro-RNAs acting as tumor suppressors or tumor promoters by targeting genes involved in the autophagy pathway.Here,we focus on the role played by non-coding RNAs-mediated regulation of autophagy in development and progression of cancers in women.Understanding how epigenetics can impact autophagy might open novel therapeutic strategies in the fight against cancers in women.
文摘Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.
文摘Hepatocellular carcinoma(HCC) is the leading primary liver cancer and its clinical outcome is still poor. MicroRNAs(mi RNAs) have demonstrated an interesting potential to regulate gene expression at post-transcriptional level. Current findings suggest that mi RNAs deregulation in cancer is caused by genetic and/or epigenetic, transcriptional and post-transcriptional modifications resulting in abnormal expression and hallmarks of malignant transformation: aberrant cell growth, cell death, differentiation, angiogenesis, invasion and metástasis. The important role of mi RNAs in the development and progression of HCC has increased the efforts to understand and develop mechanisms of control overt this single-stranded RNAs. Several studies have analyzed tumoral response to the regulation and control of deregulated mi RNAs with good results in vitro and in vivo, proving that targeting aberrant expression of mi RNAs is a powerful anticancer therapeutic. Identification of up and/or down regulated mi RNAs related to HCC has led to the discovery of new potential application for detection of their presence in the affected organism. Mi RNAs represent a relevant new target for diagnosis, prognosis and treatment in a wide variety of pathologic entities, including HCC. This manuscript intends to summarize current knowledge regarding mi RNAs and their role in HCC development.
