Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies c... more Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT.Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1−/−) were investigated by antisense inhibition and ectopic overexpression studies.Results: The copy number of let-7a3/let-7b miRNA was substantially decreas...
PDF file - 1045K, Figure S1. The comparability of whole exome sequencing for saliva and FFPE AT/R... more PDF file - 1045K, Figure S1. The comparability of whole exome sequencing for saliva and FFPE AT/RT tissue of the adult patient. The sequencing coverage folds for each chromosome of A. saliva genomic DNA and B. AT/RT genomic DNA.
PDF file - 3492K, Figure S3. Sanger DNA-sequencing for AT/RT tissue specific point mutations incl... more PDF file - 3492K, Figure S3. Sanger DNA-sequencing for AT/RT tissue specific point mutations including DBF4 (c.794C>G, p.T265S); PMS1 (c.2524C>A, p.L842I); RASSF4 (c.494A>C, p.H165P); Rap2b (c.240G>C, p.L80I); and Tie2 (c.1249C>A, p.P417T) genes. The upper panel for sequencing of genomic DNA extracted from saliva, the lower panel for AT/RT.
IntroductionMyostatin (MSTN) negatively regulates skeletal muscle development. However, its funct... more IntroductionMyostatin (MSTN) negatively regulates skeletal muscle development. However, its function in reproductive performance and visceral organs has not been thoroughly investigated. Previously, we prepared a MSTN and fibroblast growth factor 5 (FGF5) double-knockout sheep, which was a MSTN and FGF5 dual-gene biallelic homozygous (MF−/−) mutant.MethodsTo understand the role of MSTN and FGF5 in reproductive performance and visceral organs, this study evaluated the ejaculation amount, semen pH, sperm motility, sperm density, acrosome integrity, rate of teratosperm, and seminal plasma biochemical indicators in adult MF−/− rams. We also compared the overall morphology, head, head-neck junction, middle segment and the transection of middle segment of spermatozoa between wildtype (WT) and MF−/− rams.ResultsOur results showed that the seminal plasma biochemical indicators, sperm structure and all sperm indicators were normal, and the fertilization rate also has no significant differenc...
2020 7th International Forum on Electrical Engineering and Automation (IFEEA), 2020
Aiming at the problem that the ejector rod in the die-casting mold fails and loses its load-beari... more Aiming at the problem that the ejector rod in the die-casting mold fails and loses its load-bearing capacity under actual harsh conditions, this paper analyzes the failure of the ejector rod due to buckling instability from the eigenvalue buckling theory, and proposes a combination of theoretical calculation and finite element simulation analysis method. Using Workbench finite element analysis software, a finite element numerical analysis model of the experimental device that simulates the mold conditions was established. Through static simulation analysis, linear buckling analysis and nonlinear buckling analysis of the experimental device, the buckling mode, displacement, stress, strain nephogram and deflection curve of the experimental device under a given load are given. The reliability of the simulation results is proved by the mutual verification between the theoretical calculation results and the simulation results.
The development of reagentless sensors that can detect molecular analytes in biological fluids co... more The development of reagentless sensors that can detect molecular analytes in biological fluids could enable a broad range of applications in personalized health monitoring. However, only a limited set of molecular inputs can currently be detected using reagentless sensors. Here, we report a sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing method is based on the motion of an inverted molecular pendulum that exhibits field-induced transport modulated by the presence of a bound analyte. We measure the sensor's electric field-mediated transport using the electron-transfer kinetics of an attached reporter molecule. Using time-resolved electrochemical measurements that enable unidirectional motion of our sensor, the presence of an analyte bound to our sensor complex can be tracked continuously in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals.
Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and ... more Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immun...
CMV reactivation remains a significant cause of morbidity and mortality due to the extended perio... more CMV reactivation remains a significant cause of morbidity and mortality due to the extended period of immunodeficiency after allogeneic hematopoietic stem cell transplantation (HCT), despite great strides in management of the infection in the past two decades. Reconstitution of cytomegalovirus (CMV)-specific CD8+ T cells is essential to control of CMV infection in CMV-seropositive recipients (R+) after HCT. The CMV serologic status of the recipient before HCT has a strong influence on outcome. Key questions addressed in this study are the impact of donor CMV serostatus on the reconstitution of effective CMV immunity or risk of CMV reactivation and GCV usage in CMV R+ recipients. Betts and colleagues have reported that HIV-specific CD8+ T-cells which simultaneously degranulated and produced IFN-γ, TNF-α, MIP-1β and IL2 were associated with lower viral load and HIV long term non-progressor status. These findings in the context of HIV infection motivated us to investigate whether level...
Somatic cloning has had a significant impact on the life sciences and is important in a variety o... more Somatic cloning has had a significant impact on the life sciences and is important in a variety of processes, including medical research and animal production. However, the application of somatic cloning has been limited due to its low success rate. Therefore, potential epigenetic variations between cloned and donor animals are still unclear. DNA methylation, one of the factors which is responsible for phenotypic differences in animals, is a commonly researched topic in epigenetic studies of mammals. To investigate the epigenetic variations between cloned and donor animals, we selected blood and ear fibroblasts of a donor pig and a cloned pig to perform whole-genome bisulfite sequencing (WGBS). A total of 215 and 707 differential methylation genes (DMGs) were identified in blood and ear fibroblasts, respectively. Functional annotation revealed that DMGs are enriched in many pathways, including T/B or natural killer (NK) cell differentiation, oocyte maturation, embryonic development, and reproductive hormone secretion. Moreover, 22 DMGs in the blood and 75 in the ear were associated with immune responses (e.g., CD244, CDK6, CD5, CD2, CD83, and CDC7). We also found that 18 DMGs in blood and 53 in ear fibroblasts were involved in reproduction. Understanding the expression patterns of DMGs, especially in relation to immune responses and reproduction, will reveal insights that will aid the advancement of future somatic cloning techniques in swine.
Recently, a phenotype of CD8+ T cells was discovered that distinguishes long-term non-progressors... more Recently, a phenotype of CD8+ T cells was discovered that distinguishes long-term non-progressors from rapid progressors in HIV infection. The phenotype consists of a combination of cytokines and the CD107 surface marker, associated with competence for cytotoxicity, all expressed from the same CD8+ T cell. Our published work highlighted a significant difference in frequency of IFN-γ and TNF-α double cytokine expressing T cells, which are more frequently associated with CMV-positive than negative donors of stem cell transplants (HCT). Both clinical and basic studies have shown that TNF-α expression is associated with mature immunity, and its proper regulation is associated with a favorable outcome of HCT. We investigated the quality of T cell immunity targeting the CMV-pp65 antigen in a longitudinal study of HCT recipients up to 1 year post-Tx. HCT recipients with both CMV-positive and negative donors were accrued, and differences were compared between the two cohorts based on single...
2054 Poster Board II-31 The serine proteinases, human neutrophil elastase (HNE) and proteinase 3 ... more 2054 Poster Board II-31 The serine proteinases, human neutrophil elastase (HNE) and proteinase 3 (PR3) are degradative enzymes stored in cytoplasmic azurophilic granules of neutrophils. Both proteins are aberrantly expressed in human myeloid leukemias. Over-expression of PR3 is important in maintaining a leukemia phenotype, while HNE may suppress hematopoietic progenitors. PR3 and HNE contain a conserved nonameric HLA-A*02 restricted T-cell epitope called PR1. The presence of PR1-specific CTL has been correlated with molecular remission in CML. A PR1 nonameric peptide vaccine has been evaluated clinically, with promising results. A limitation of the PR1 peptide vaccine is its restriction to patients with the HLA-A*02 allele. A vaccine comprising a larger portion of the PR3 and/or HNE protein and capable of inducing broader T-cell responses restricted by a wider range of HLA alleles is a potential alternative. We have generated numerous recombinant vaccinia viruses (rVV) expressing f...
The ex vivo expansion of hematopoietic stem cells is significantly inhibited by secreted proteins... more The ex vivo expansion of hematopoietic stem cells is significantly inhibited by secreted proteins that induce negative feedback loops. The ability to effectively monitor these factors is critical for their real-time regulation and control and, by extension, enhancing stem cell expansion. Here, we describe a novel monitoring strategy for the detection of soluble signaling factors in stem cell cultures using a DNA-based sensing mechanism on a chip-based nanostructured microelectrode platform. We combine DNA hybridization engineering with antibody-capturing chemistry in an amplified steric hindrance hybridization assay. This method enables the quantification of important secreted proteins, showcased by the detection of 10 pg·mL level concentrations of three proteins in stem cell culture samples. This approach is the first universal nonsandwich technique that permits pg·mL level quantification of small proteins in stem cell culture media without signal loss.
American Chemical Society after peer review and technical editing by the publisher. To access the... more American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see 10.1021/acsnano.8b07616. How to cite TSpace items Always cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page. This article was made openly accessible by U of T Faculty. Please tell us how this access benefits you. Your story matters.
Carcinosarcoma comprises less than 0.1% primary pancreatic neoplasms and is associated with a poo... more Carcinosarcoma comprises less than 0.1% primary pancreatic neoplasms and is associated with a poor prognosis. The histogenesis remains unknown. We hypothesize that pancreatic carcinosarcoms is a form of an existing carcinoma that undergoes a metaplastic transformation into its sarcomatous component and expresses epithelial to mesenchymal transition markers. In 2 cases of pancreatic carcinosarcoma with osteoclasts-like giant cells, we tested the expression of epithelial to mesenchymal transition markers HMGA2, ZEB1, and E-cadherin and expression of p53 using immunohistochemistry. Both adenocarcinoma and sarcomatous component express p53, HMGA2, and ZEB1, with the sarcomatous area showing much stronger and diffuse staining. E-cadherin expression is retained in carcinocarcinoma, whereas it is aberrant in all sarcoma components. We provide, for the first time, in situ evidence that epithelial to mesenchymal transition is present in pancreatic carcinosarcoma and support the monoclonal origin of these 2 distinct components in this rare malignancy.
Archives of Pathology & Laboratory Medicine, 2017
Context.—Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly ... more Context.—Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas.Objectives.—To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields.Data Sources.—Data sources include literature review, authors' research data, and personal practice experience.Conclusions.—Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neo...
Epilepsy is linked to mutations in KCNQ channels. KCNQ channels including KCNQ2 and KCNQ3 are enr... more Epilepsy is linked to mutations in KCNQ channels. KCNQ channels including KCNQ2 and KCNQ3 are enriched in neurons, regulating action potential generation and modulation. Here, we showed that properties of KCNQ2 channel in rat hippocampal cultured neurons are regulated by ubiquitous calcium sensor calmodulin. We analyzed calmodulin function on the KCNQ2 channel in both HEK293 cells and neurons. We used shRNAs to suppress expression of calmodulin protein. On the other hand, we used cDNA to over-express calmodulin in HEK293 and neuron cells. In wild type and mis-sense mutations of KCNQ2 proteins, calmodulin over-expression enhanced outward K(+) current and decreased neuronal activity. Meanwhile, calmodulin knockdown reduced KCNQ2 current and increased neuronal activity, showing that hippocampal neuronal excitability is regulated by expression level of calmodulin protein. Our data suggest that calmodulin performs a major function in regulating KCNQ2 properties via direct binding to KCNQ...
Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies c... more Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT.Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1−/−) were investigated by antisense inhibition and ectopic overexpression studies.Results: The copy number of let-7a3/let-7b miRNA was substantially decreas...
PDF file - 1045K, Figure S1. The comparability of whole exome sequencing for saliva and FFPE AT/R... more PDF file - 1045K, Figure S1. The comparability of whole exome sequencing for saliva and FFPE AT/RT tissue of the adult patient. The sequencing coverage folds for each chromosome of A. saliva genomic DNA and B. AT/RT genomic DNA.
PDF file - 3492K, Figure S3. Sanger DNA-sequencing for AT/RT tissue specific point mutations incl... more PDF file - 3492K, Figure S3. Sanger DNA-sequencing for AT/RT tissue specific point mutations including DBF4 (c.794C>G, p.T265S); PMS1 (c.2524C>A, p.L842I); RASSF4 (c.494A>C, p.H165P); Rap2b (c.240G>C, p.L80I); and Tie2 (c.1249C>A, p.P417T) genes. The upper panel for sequencing of genomic DNA extracted from saliva, the lower panel for AT/RT.
IntroductionMyostatin (MSTN) negatively regulates skeletal muscle development. However, its funct... more IntroductionMyostatin (MSTN) negatively regulates skeletal muscle development. However, its function in reproductive performance and visceral organs has not been thoroughly investigated. Previously, we prepared a MSTN and fibroblast growth factor 5 (FGF5) double-knockout sheep, which was a MSTN and FGF5 dual-gene biallelic homozygous (MF−/−) mutant.MethodsTo understand the role of MSTN and FGF5 in reproductive performance and visceral organs, this study evaluated the ejaculation amount, semen pH, sperm motility, sperm density, acrosome integrity, rate of teratosperm, and seminal plasma biochemical indicators in adult MF−/− rams. We also compared the overall morphology, head, head-neck junction, middle segment and the transection of middle segment of spermatozoa between wildtype (WT) and MF−/− rams.ResultsOur results showed that the seminal plasma biochemical indicators, sperm structure and all sperm indicators were normal, and the fertilization rate also has no significant differenc...
2020 7th International Forum on Electrical Engineering and Automation (IFEEA), 2020
Aiming at the problem that the ejector rod in the die-casting mold fails and loses its load-beari... more Aiming at the problem that the ejector rod in the die-casting mold fails and loses its load-bearing capacity under actual harsh conditions, this paper analyzes the failure of the ejector rod due to buckling instability from the eigenvalue buckling theory, and proposes a combination of theoretical calculation and finite element simulation analysis method. Using Workbench finite element analysis software, a finite element numerical analysis model of the experimental device that simulates the mold conditions was established. Through static simulation analysis, linear buckling analysis and nonlinear buckling analysis of the experimental device, the buckling mode, displacement, stress, strain nephogram and deflection curve of the experimental device under a given load are given. The reliability of the simulation results is proved by the mutual verification between the theoretical calculation results and the simulation results.
The development of reagentless sensors that can detect molecular analytes in biological fluids co... more The development of reagentless sensors that can detect molecular analytes in biological fluids could enable a broad range of applications in personalized health monitoring. However, only a limited set of molecular inputs can currently be detected using reagentless sensors. Here, we report a sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing method is based on the motion of an inverted molecular pendulum that exhibits field-induced transport modulated by the presence of a bound analyte. We measure the sensor's electric field-mediated transport using the electron-transfer kinetics of an attached reporter molecule. Using time-resolved electrochemical measurements that enable unidirectional motion of our sensor, the presence of an analyte bound to our sensor complex can be tracked continuously in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals.
Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and ... more Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immun...
CMV reactivation remains a significant cause of morbidity and mortality due to the extended perio... more CMV reactivation remains a significant cause of morbidity and mortality due to the extended period of immunodeficiency after allogeneic hematopoietic stem cell transplantation (HCT), despite great strides in management of the infection in the past two decades. Reconstitution of cytomegalovirus (CMV)-specific CD8+ T cells is essential to control of CMV infection in CMV-seropositive recipients (R+) after HCT. The CMV serologic status of the recipient before HCT has a strong influence on outcome. Key questions addressed in this study are the impact of donor CMV serostatus on the reconstitution of effective CMV immunity or risk of CMV reactivation and GCV usage in CMV R+ recipients. Betts and colleagues have reported that HIV-specific CD8+ T-cells which simultaneously degranulated and produced IFN-γ, TNF-α, MIP-1β and IL2 were associated with lower viral load and HIV long term non-progressor status. These findings in the context of HIV infection motivated us to investigate whether level...
Somatic cloning has had a significant impact on the life sciences and is important in a variety o... more Somatic cloning has had a significant impact on the life sciences and is important in a variety of processes, including medical research and animal production. However, the application of somatic cloning has been limited due to its low success rate. Therefore, potential epigenetic variations between cloned and donor animals are still unclear. DNA methylation, one of the factors which is responsible for phenotypic differences in animals, is a commonly researched topic in epigenetic studies of mammals. To investigate the epigenetic variations between cloned and donor animals, we selected blood and ear fibroblasts of a donor pig and a cloned pig to perform whole-genome bisulfite sequencing (WGBS). A total of 215 and 707 differential methylation genes (DMGs) were identified in blood and ear fibroblasts, respectively. Functional annotation revealed that DMGs are enriched in many pathways, including T/B or natural killer (NK) cell differentiation, oocyte maturation, embryonic development, and reproductive hormone secretion. Moreover, 22 DMGs in the blood and 75 in the ear were associated with immune responses (e.g., CD244, CDK6, CD5, CD2, CD83, and CDC7). We also found that 18 DMGs in blood and 53 in ear fibroblasts were involved in reproduction. Understanding the expression patterns of DMGs, especially in relation to immune responses and reproduction, will reveal insights that will aid the advancement of future somatic cloning techniques in swine.
Recently, a phenotype of CD8+ T cells was discovered that distinguishes long-term non-progressors... more Recently, a phenotype of CD8+ T cells was discovered that distinguishes long-term non-progressors from rapid progressors in HIV infection. The phenotype consists of a combination of cytokines and the CD107 surface marker, associated with competence for cytotoxicity, all expressed from the same CD8+ T cell. Our published work highlighted a significant difference in frequency of IFN-γ and TNF-α double cytokine expressing T cells, which are more frequently associated with CMV-positive than negative donors of stem cell transplants (HCT). Both clinical and basic studies have shown that TNF-α expression is associated with mature immunity, and its proper regulation is associated with a favorable outcome of HCT. We investigated the quality of T cell immunity targeting the CMV-pp65 antigen in a longitudinal study of HCT recipients up to 1 year post-Tx. HCT recipients with both CMV-positive and negative donors were accrued, and differences were compared between the two cohorts based on single...
2054 Poster Board II-31 The serine proteinases, human neutrophil elastase (HNE) and proteinase 3 ... more 2054 Poster Board II-31 The serine proteinases, human neutrophil elastase (HNE) and proteinase 3 (PR3) are degradative enzymes stored in cytoplasmic azurophilic granules of neutrophils. Both proteins are aberrantly expressed in human myeloid leukemias. Over-expression of PR3 is important in maintaining a leukemia phenotype, while HNE may suppress hematopoietic progenitors. PR3 and HNE contain a conserved nonameric HLA-A*02 restricted T-cell epitope called PR1. The presence of PR1-specific CTL has been correlated with molecular remission in CML. A PR1 nonameric peptide vaccine has been evaluated clinically, with promising results. A limitation of the PR1 peptide vaccine is its restriction to patients with the HLA-A*02 allele. A vaccine comprising a larger portion of the PR3 and/or HNE protein and capable of inducing broader T-cell responses restricted by a wider range of HLA alleles is a potential alternative. We have generated numerous recombinant vaccinia viruses (rVV) expressing f...
The ex vivo expansion of hematopoietic stem cells is significantly inhibited by secreted proteins... more The ex vivo expansion of hematopoietic stem cells is significantly inhibited by secreted proteins that induce negative feedback loops. The ability to effectively monitor these factors is critical for their real-time regulation and control and, by extension, enhancing stem cell expansion. Here, we describe a novel monitoring strategy for the detection of soluble signaling factors in stem cell cultures using a DNA-based sensing mechanism on a chip-based nanostructured microelectrode platform. We combine DNA hybridization engineering with antibody-capturing chemistry in an amplified steric hindrance hybridization assay. This method enables the quantification of important secreted proteins, showcased by the detection of 10 pg·mL level concentrations of three proteins in stem cell culture samples. This approach is the first universal nonsandwich technique that permits pg·mL level quantification of small proteins in stem cell culture media without signal loss.
American Chemical Society after peer review and technical editing by the publisher. To access the... more American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see 10.1021/acsnano.8b07616. How to cite TSpace items Always cite the published version, so the author(s) will receive recognition through services that track citation counts, e.g. Scopus. If you need to cite the page number of the author manuscript from TSpace because you cannot access the published version, then cite the TSpace version in addition to the published version using the permanent URI (handle) found on the record page. This article was made openly accessible by U of T Faculty. Please tell us how this access benefits you. Your story matters.
Carcinosarcoma comprises less than 0.1% primary pancreatic neoplasms and is associated with a poo... more Carcinosarcoma comprises less than 0.1% primary pancreatic neoplasms and is associated with a poor prognosis. The histogenesis remains unknown. We hypothesize that pancreatic carcinosarcoms is a form of an existing carcinoma that undergoes a metaplastic transformation into its sarcomatous component and expresses epithelial to mesenchymal transition markers. In 2 cases of pancreatic carcinosarcoma with osteoclasts-like giant cells, we tested the expression of epithelial to mesenchymal transition markers HMGA2, ZEB1, and E-cadherin and expression of p53 using immunohistochemistry. Both adenocarcinoma and sarcomatous component express p53, HMGA2, and ZEB1, with the sarcomatous area showing much stronger and diffuse staining. E-cadherin expression is retained in carcinocarcinoma, whereas it is aberrant in all sarcoma components. We provide, for the first time, in situ evidence that epithelial to mesenchymal transition is present in pancreatic carcinosarcoma and support the monoclonal origin of these 2 distinct components in this rare malignancy.
Archives of Pathology & Laboratory Medicine, 2017
Context.—Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly ... more Context.—Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas.Objectives.—To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields.Data Sources.—Data sources include literature review, authors' research data, and personal practice experience.Conclusions.—Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neo...
Epilepsy is linked to mutations in KCNQ channels. KCNQ channels including KCNQ2 and KCNQ3 are enr... more Epilepsy is linked to mutations in KCNQ channels. KCNQ channels including KCNQ2 and KCNQ3 are enriched in neurons, regulating action potential generation and modulation. Here, we showed that properties of KCNQ2 channel in rat hippocampal cultured neurons are regulated by ubiquitous calcium sensor calmodulin. We analyzed calmodulin function on the KCNQ2 channel in both HEK293 cells and neurons. We used shRNAs to suppress expression of calmodulin protein. On the other hand, we used cDNA to over-express calmodulin in HEK293 and neuron cells. In wild type and mis-sense mutations of KCNQ2 proteins, calmodulin over-expression enhanced outward K(+) current and decreased neuronal activity. Meanwhile, calmodulin knockdown reduced KCNQ2 current and increased neuronal activity, showing that hippocampal neuronal excitability is regulated by expression level of calmodulin protein. Our data suggest that calmodulin performs a major function in regulating KCNQ2 properties via direct binding to KCNQ...
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