X. Xi, Jing Zhang, Jian Wang, Yuqin Chen, Wenmei Zhang, Xiao-ping Zhang, Jie Du, G. Zhu
Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1−/− mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1−/− macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment.
{"title":"SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation","authors":"X. Xi, Jing Zhang, Jian Wang, Yuqin Chen, Wenmei Zhang, Xiao-ping Zhang, Jie Du, G. Zhu","doi":"10.1155/2019/3013765","DOIUrl":"https://doi.org/10.1155/2019/3013765","url":null,"abstract":"Inflammation plays a pivotal role in the development of pulmonary arterial hypertension (PAH). Meanwhile, serum glucocorticoid-regulated kinase-1 (SGK1) has been considered to be an important factor in the regulation of inflammation in some vascular disease. However, the role of SGK1 in hypoxia-induced inflammation and PAH is still unknown. WT and SGK1−/− mice were exposed to chronic hypoxia to induce PAH. The quantitative PCR and immunohistochemistry were used to determine the expression of SGK1. The right ventricular hypertrophy index (RVHI), RV/BW ratio, right ventricle systolic pressure (RVSP), and percentage of muscularised vessels and medical wall thickness were measured to evaluate PAH development. The infiltration of macrophages and localization of SGK1 on cells were examined by histological analysis. The effects of SGK1 on macrophage function and cytokine expression were assessed by comparing WT and SGK1−/− macrophages in vitro. SGK1 has high expression in hypoxia-induced PAH. Deficiency of SGK1 prevented the development of hypoxia-induced PAH and inhibited macrophage infiltration in the lung. In addition, SGK1 knockout inhibited the expression of proinflammatory cytokines in macrophages. SGK1-induced macrophage activation and proinflammatory response contributes to the development of PAH in hypoxia-treated mice. Thus, SGK1 might be considered a promising target for PAH treatment.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115739468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In patients with non-small-cell lung carcinoma (NSCLC), the analysis of BRAF V600E mutation has become more and more applied since the introduction of many mutation-targeted medications. In this regard, the advantage of immunohistochemistry (IHC) as a reliable diagnostic test substitute to other molecular studies has not been approved yet. Objective. To examine the dependability of using immunohistochemical method utilizing monoclonal VE1 antibody in the detection of BRAF V600 E mutation in patients with non-small-cell lung carcinoma and compare the results there with that of polymerase chain reaction (SSCP-PCR). Materials and Methods. We retrospectively identified 53 patients of whom their histopathological diagnosis was non-small-cell carcinoma of different types. Evaluation of BRAF V600E mutation was assessed using polymerase chain reaction (SSCP-PCR) and IHC using VE1 antibody. This approach was applied to all cases under the study. Results. Among the 53 NSCLC samples, only 5 (9.3%) cases harbored BRAF V600E mutation, 80% were of adenocarcinoma type, and the rest (20%) was of squamous cell carcinoma. IHC analysis for VE1 was positive in 4 out of 5 (80%) BRAF-mutated tumors and negative in all nonmutated BRAF V600 E NSCLC. Conclusion. Our results revealed that VE1 antibody IHC analysis is a promising technique that can be used to detect BRAF V600-mutated NSCLC with relatively high specificity and sensitivity and might become a potential alternative to the current molecular biological methods that are in use for this purpose.
{"title":"Immunohistochemical Study Using Monoclonal VE1 Antibody Can Substitute the Molecular Tests for Apprehension of BRAF V600E Mutation in Patients with Non-small-Cell Lung Carcinoma","authors":"H. Karbel, S. S. Ejam, A. Naji","doi":"10.1155/2019/2315673","DOIUrl":"https://doi.org/10.1155/2019/2315673","url":null,"abstract":"In patients with non-small-cell lung carcinoma (NSCLC), the analysis of BRAF V600E mutation has become more and more applied since the introduction of many mutation-targeted medications. In this regard, the advantage of immunohistochemistry (IHC) as a reliable diagnostic test substitute to other molecular studies has not been approved yet. Objective. To examine the dependability of using immunohistochemical method utilizing monoclonal VE1 antibody in the detection of BRAF V600 E mutation in patients with non-small-cell lung carcinoma and compare the results there with that of polymerase chain reaction (SSCP-PCR). Materials and Methods. We retrospectively identified 53 patients of whom their histopathological diagnosis was non-small-cell carcinoma of different types. Evaluation of BRAF V600E mutation was assessed using polymerase chain reaction (SSCP-PCR) and IHC using VE1 antibody. This approach was applied to all cases under the study. Results. Among the 53 NSCLC samples, only 5 (9.3%) cases harbored BRAF V600E mutation, 80% were of adenocarcinoma type, and the rest (20%) was of squamous cell carcinoma. IHC analysis for VE1 was positive in 4 out of 5 (80%) BRAF-mutated tumors and negative in all nonmutated BRAF V600 E NSCLC. Conclusion. Our results revealed that VE1 antibody IHC analysis is a promising technique that can be used to detect BRAF V600-mutated NSCLC with relatively high specificity and sensitivity and might become a potential alternative to the current molecular biological methods that are in use for this purpose.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"BME-32 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114120773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Ku, Yan Xu, Chunlin Cai, Yili Yang, L. Cui, Wei Yan
Liver metastasis is the most common form of metastatic colorectal cancers during the course of the disease. The global change in protein abundance in liver metastatic colorectal cancers and its role in metastasis establishment have not been comprehensively analyzed. In the present study, fresh-frozen tissue samples including normal colon/localized/liver metastatic CRCs from each recruited patient were analyzed by quantitative proteomics using a multiplexed TMT labeling strategy. Around 5000 protein groups were quantified from all samples. The proteomic profile of localized/metastatic CRCs varied greatly from that of normal colon tissues; differential proteins were mainly from extracellular regions and participate in immune activities, which is crucial for the chronic inflammation signaling pathways in the tumor microenvironment. Further statistical analysis revealed 47 proteins exhibiting statistical significance between localized and metastatic CRCs, of which FILI1P1 and PLG were identified for the first time in proteomic data, which were highly associated with liver metastasis in CRCs.
{"title":"In-Depth Characterization of Mass Spectrometry-Based Proteomic Profiles Revealed Novel Signature Proteins Associated with Liver Metastatic Colorectal Cancers","authors":"Xin Ku, Yan Xu, Chunlin Cai, Yili Yang, L. Cui, Wei Yan","doi":"10.1155/2019/7653230","DOIUrl":"https://doi.org/10.1155/2019/7653230","url":null,"abstract":"Liver metastasis is the most common form of metastatic colorectal cancers during the course of the disease. The global change in protein abundance in liver metastatic colorectal cancers and its role in metastasis establishment have not been comprehensively analyzed. In the present study, fresh-frozen tissue samples including normal colon/localized/liver metastatic CRCs from each recruited patient were analyzed by quantitative proteomics using a multiplexed TMT labeling strategy. Around 5000 protein groups were quantified from all samples. The proteomic profile of localized/metastatic CRCs varied greatly from that of normal colon tissues; differential proteins were mainly from extracellular regions and participate in immune activities, which is crucial for the chronic inflammation signaling pathways in the tumor microenvironment. Further statistical analysis revealed 47 proteins exhibiting statistical significance between localized and metastatic CRCs, of which FILI1P1 and PLG were identified for the first time in proteomic data, which were highly associated with liver metastasis in CRCs.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"263 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132517647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Neagu, C. Constantin, M. Bostan, C. Caruntu, Simona-Rebeca Ignat, S. Dinescu, M. Costache
The epithelial-mesenchymal transition (EMT) is a complex transformation process that induces local and distant progression of many malignant tumours. Due to its complex array of proteins that are dynamically over-/underexpressed during this process, proteomic technologies gained their place in the EMT research in the last years. Proteomics has identified new molecular pathways of this process and brought important insights to develop new therapy targets. Various proteomic tools and multiple combinations were developed in this area. Out of the proteomic technology armentarium, mass spectrometry and array technologies are the most used approaches. The main characteristics of the proteomic technology used in this domain are high throughput and detection of minute concentration in small samples. We present herein, using various proteomic technologies, the identification in cancer cell lines and in tumour tissue EMT-related proteins, proteins that are involved in the activation of different cellular pathways. Proteomics has brought besides standard EMT markers (e.g., cell-cell adhesion proteins and transcription factors) other future potential markers for improving diagnosis, monitoring evolution, and developing new therapy targets. Future will increase the proteomic role in clinical investigation and validation of EMT-related biomarkers.
{"title":"Proteomic Technology “Lens” for Epithelial-Mesenchymal Transition Process Identification in Oncology","authors":"M. Neagu, C. Constantin, M. Bostan, C. Caruntu, Simona-Rebeca Ignat, S. Dinescu, M. Costache","doi":"10.1155/2019/3565970","DOIUrl":"https://doi.org/10.1155/2019/3565970","url":null,"abstract":"The epithelial-mesenchymal transition (EMT) is a complex transformation process that induces local and distant progression of many malignant tumours. Due to its complex array of proteins that are dynamically over-/underexpressed during this process, proteomic technologies gained their place in the EMT research in the last years. Proteomics has identified new molecular pathways of this process and brought important insights to develop new therapy targets. Various proteomic tools and multiple combinations were developed in this area. Out of the proteomic technology armentarium, mass spectrometry and array technologies are the most used approaches. The main characteristics of the proteomic technology used in this domain are high throughput and detection of minute concentration in small samples. We present herein, using various proteomic technologies, the identification in cancer cell lines and in tumour tissue EMT-related proteins, proteins that are involved in the activation of different cellular pathways. Proteomics has brought besides standard EMT markers (e.g., cell-cell adhesion proteins and transcription factors) other future potential markers for improving diagnosis, monitoring evolution, and developing new therapy targets. Future will increase the proteomic role in clinical investigation and validation of EMT-related biomarkers.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123967440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Aly, H. Fetaih, A. Hassanin, M. Abomughaid, A. A. Ismail
Natural oils are traditional medicinal herbs, which have attracted interests for its potential anti-inflammatory and anticancer activities. The present work is aimed at evaluating the protective effect of garlic oil and cinnamon oil on diethylnitrosamine- (DENA-) and 2-acetylaminofluorene- (2-AAF-) induced p53 gene mutation and hepatocarcinogenesis in rats. Forty male albino rats were divided into 4 equal groups: control, hepatocellular carcinoma (HCC), garlic oil-HCC, and cinnamon oil-HCC. The HCC-induced group showed a significant decrease in the body mass and a significant elevation in the liver weight, alpha-fetoprotein (AFP), liver enzymes, hepatic malondialdehyde (MDA), and p53 protein expression levels as well as genetic mutations in intron 5 of p53 gene in the form of Single-Nucleotide Polymorphisms (SNPs) and insertions. In addition, the glutathione (GSH) level and superoxide dismutase (SOD) activities were increased. While HCC rats pretreated with garlic oil or cinnamon oil were significantly reversed, these destructive actions increased GSH and SOD levels. The HCC-induced group showed histopathological features of liver cancer including hypercellularity, nuclear hyperchromasia, mitotic figures, and preneoplastic foci. On the other hand, HCC rats pretreated with garlic oil or cinnamon oil revealed partial reversal of normal liver architecture. The present findings proposed that these natural oils have the ability to improve liver function, significantly reduced the liver toxicity and HCC development. However, further sophisticated studies are recommended before their use as conventional therapeutics for HCC treatment.
{"title":"Protective Effects of Garlic and Cinnamon Oils on Hepatocellular Carcinoma in Albino Rats","authors":"S. Aly, H. Fetaih, A. Hassanin, M. Abomughaid, A. A. Ismail","doi":"10.1155/2019/9895485","DOIUrl":"https://doi.org/10.1155/2019/9895485","url":null,"abstract":"Natural oils are traditional medicinal herbs, which have attracted interests for its potential anti-inflammatory and anticancer activities. The present work is aimed at evaluating the protective effect of garlic oil and cinnamon oil on diethylnitrosamine- (DENA-) and 2-acetylaminofluorene- (2-AAF-) induced p53 gene mutation and hepatocarcinogenesis in rats. Forty male albino rats were divided into 4 equal groups: control, hepatocellular carcinoma (HCC), garlic oil-HCC, and cinnamon oil-HCC. The HCC-induced group showed a significant decrease in the body mass and a significant elevation in the liver weight, alpha-fetoprotein (AFP), liver enzymes, hepatic malondialdehyde (MDA), and p53 protein expression levels as well as genetic mutations in intron 5 of p53 gene in the form of Single-Nucleotide Polymorphisms (SNPs) and insertions. In addition, the glutathione (GSH) level and superoxide dismutase (SOD) activities were increased. While HCC rats pretreated with garlic oil or cinnamon oil were significantly reversed, these destructive actions increased GSH and SOD levels. The HCC-induced group showed histopathological features of liver cancer including hypercellularity, nuclear hyperchromasia, mitotic figures, and preneoplastic foci. On the other hand, HCC rats pretreated with garlic oil or cinnamon oil revealed partial reversal of normal liver architecture. The present findings proposed that these natural oils have the ability to improve liver function, significantly reduced the liver toxicity and HCC development. However, further sophisticated studies are recommended before their use as conventional therapeutics for HCC treatment.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"264 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134209531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huanhuan Zuo, Xiaochen Xie, J. Peng, Lixin Wang, R. Zhu
Recently, there has been an increasing interest in the potential clinical use of several inflammatory indexes, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-immune-inflammation index (SII). This study aimed at assessing whether these markers could be early indicators of pulmonary hypertension (PH) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 185 patients were enrolled in our retrospective study from January 2017 to January 2019. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the clinical significance of these biomarkers to predict PH in patients with AECOPD. According to the diagnostic criterion for PH by Doppler echocardiography, the patients were stratified into two groups. The study group consisted of 101 patients complicated with PH, and the control group had 84 patients. The NLR, PLR, and SII values of the PH group were significantly higher than those of the AECOPD one (p < 0.05). The blood biomarker levels were positively correlated with NT-proBNP levels, while they had no significant correlation with the estimated pulmonary arterial systolic pressure (PASP) other than PLR. NLR, PLR, and SII values were all associated with PH (p < 0.05) in the univariate analysis, but not in the multivariate analysis. The AUC of NLR used for predicting PH was 0.701 and was higher than PLR and SII. Using 4.659 as the cut-off value of NLR, the sensitivity was 81.2%, and the specificity was 59.5%. In conclusion, these simple markers may be useful in the prediction of PH in patients with AECOPD.
{"title":"Predictive Value of Novel Inflammation-Based Biomarkers for Pulmonary Hypertension in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease","authors":"Huanhuan Zuo, Xiaochen Xie, J. Peng, Lixin Wang, R. Zhu","doi":"10.1155/2019/5189165","DOIUrl":"https://doi.org/10.1155/2019/5189165","url":null,"abstract":"Recently, there has been an increasing interest in the potential clinical use of several inflammatory indexes, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-immune-inflammation index (SII). This study aimed at assessing whether these markers could be early indicators of pulmonary hypertension (PH) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 185 patients were enrolled in our retrospective study from January 2017 to January 2019. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the clinical significance of these biomarkers to predict PH in patients with AECOPD. According to the diagnostic criterion for PH by Doppler echocardiography, the patients were stratified into two groups. The study group consisted of 101 patients complicated with PH, and the control group had 84 patients. The NLR, PLR, and SII values of the PH group were significantly higher than those of the AECOPD one (p < 0.05). The blood biomarker levels were positively correlated with NT-proBNP levels, while they had no significant correlation with the estimated pulmonary arterial systolic pressure (PASP) other than PLR. NLR, PLR, and SII values were all associated with PH (p < 0.05) in the univariate analysis, but not in the multivariate analysis. The AUC of NLR used for predicting PH was 0.701 and was higher than PLR and SII. Using 4.659 as the cut-off value of NLR, the sensitivity was 81.2%, and the specificity was 59.5%. In conclusion, these simple markers may be useful in the prediction of PH in patients with AECOPD.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"17 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125620036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Altun, H. Yazici, E. Arslan, K. G. Tulaci, H. Erken
Objective To evaluate the effect of streptozotocin-induced experimental diabetes mellitus on p16, p53, Ki67, and Bcl2 expressions and histopathological changes in the tongue of the rats. Material and Methods Twenty-two adult female Sprague-Dawley rats were used. The rats were randomly divided into 2 groups (n = 14) as control (C) (n = 8) and diabetic (DM) (n = 6). The rats in the DM group were given streptozotocin as a single intraperitoneal dose for induction of diabetes. Histopathological and immunohistochemical evaluations of formalin-fixed and paraffin-embedded tissue sections of the tongue were used. Results Significant differences were observed between the DM group and the control group in terms of epithelial thickness, length of filiform papillae, and width of filiform papillae (p = 0.005, p = 0.001, and p = 0.006, respectively). There was no significant difference between the groups in terms of mononuclear inflammatory cell infiltration, capillary proliferation, and dysplasia (p = 0.204, p = 0.244, and p = 0.204, respectively). As a result of immunohistochemical studies, no significant difference was found between the groups in terms of p53, Ki67, and Bcl-2 expressions (p = 0.588, p = 0.662, and p = 0.686, respectively). A significant difference was found between the groups when p16 expression was evaluated (p = 0.006). Conclusions In our study, streptozotocin-induced experimental diabetes mellitus induced p16 expression but did not show any difference in p53, Bcl-2, and Ki67 levels. It should be considered in the studies that the pathological changes at the early stages of the relationship between DM and oral cancer may be related to p16 expression; however, it may also be linked with p16-related aging process.
{"title":"The Impact of Type II Diabetes on Tongue Dysplasia and p16-Related Aging Process: An Experimental Study","authors":"E. Altun, H. Yazici, E. Arslan, K. G. Tulaci, H. Erken","doi":"10.1155/2019/3563215","DOIUrl":"https://doi.org/10.1155/2019/3563215","url":null,"abstract":"Objective To evaluate the effect of streptozotocin-induced experimental diabetes mellitus on p16, p53, Ki67, and Bcl2 expressions and histopathological changes in the tongue of the rats. Material and Methods Twenty-two adult female Sprague-Dawley rats were used. The rats were randomly divided into 2 groups (n = 14) as control (C) (n = 8) and diabetic (DM) (n = 6). The rats in the DM group were given streptozotocin as a single intraperitoneal dose for induction of diabetes. Histopathological and immunohistochemical evaluations of formalin-fixed and paraffin-embedded tissue sections of the tongue were used. Results Significant differences were observed between the DM group and the control group in terms of epithelial thickness, length of filiform papillae, and width of filiform papillae (p = 0.005, p = 0.001, and p = 0.006, respectively). There was no significant difference between the groups in terms of mononuclear inflammatory cell infiltration, capillary proliferation, and dysplasia (p = 0.204, p = 0.244, and p = 0.204, respectively). As a result of immunohistochemical studies, no significant difference was found between the groups in terms of p53, Ki67, and Bcl-2 expressions (p = 0.588, p = 0.662, and p = 0.686, respectively). A significant difference was found between the groups when p16 expression was evaluated (p = 0.006). Conclusions In our study, streptozotocin-induced experimental diabetes mellitus induced p16 expression but did not show any difference in p53, Bcl-2, and Ki67 levels. It should be considered in the studies that the pathological changes at the early stages of the relationship between DM and oral cancer may be related to p16 expression; however, it may also be linked with p16-related aging process.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"92 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132881042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite enormous advances being made in diagnosis and therapeutic interventions, pancreatic ductal adenocarcinoma (PDAC) is still recognized as one of the most lethal malignancies. Early diagnosis and timely curative surgery can markedly improve the prognosis; hence, there is an unmet necessity to explore efficient biomarkers for patients' benefit. Recently, blood miRNAs (miRNAs) have been reported to be a novel biomarker in human cancers. Part of it is selectively packaged by plasma exosomes released from cells via exocytosis and is highly sensitive to changes in the tumor microenvironment. Furthermore, due to less invasiveness and technical availability, miRNA-based liquid biopsy holds promise for further wide usage. Therefore, this review is aimed at presenting an update on the association between blood miRNAs and the biology of PDAC, then discussing its clinical utilization further.
{"title":"The State of the Art on Blood MicroRNAs in Pancreatic Ductal Adenocarcinoma","authors":"Zhuqing Gao, Wei Jiang, Shutian Zhang, Peng Li","doi":"10.1155/2019/9419072","DOIUrl":"https://doi.org/10.1155/2019/9419072","url":null,"abstract":"Despite enormous advances being made in diagnosis and therapeutic interventions, pancreatic ductal adenocarcinoma (PDAC) is still recognized as one of the most lethal malignancies. Early diagnosis and timely curative surgery can markedly improve the prognosis; hence, there is an unmet necessity to explore efficient biomarkers for patients' benefit. Recently, blood miRNAs (miRNAs) have been reported to be a novel biomarker in human cancers. Part of it is selectively packaged by plasma exosomes released from cells via exocytosis and is highly sensitive to changes in the tumor microenvironment. Furthermore, due to less invasiveness and technical availability, miRNA-based liquid biopsy holds promise for further wide usage. Therefore, this review is aimed at presenting an update on the association between blood miRNAs and the biology of PDAC, then discussing its clinical utilization further.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126109606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction and antiangiogenesis effect of Rg3 on orthotopic HCC in vivo. Methods The murine HCC cells Hep1-6 were implanted in the liver of mouse. With oral feeding of Rg3 (10 mg/kg once a day for 30 days), the quantitative analysis of apoptosis was performed by using pathology and a transmission electron microscope and microvessel density was quantitatively measured by immunohistochemical staining of the CD105 antibody. The mice treated with Rg3 (n = 10) were compared with the control (n = 10) using Kaplan-Meier analysis. Animal weight and tumor weight were measured to determine the toxicity of Rg3 and antitumor effect on an orthotopic HCC tumor model. Results With oral feeding of Rg3 daily in the first 30 days on tumor implantation, Rg3 significantly decreased the orthotopic tumor growth and increased the survival of animals (P < 0.05). Rg3-treated mice showed a longer survival than the control (P < 0.05). Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor apoptotic progress, which then weakened the tumor volume and its capability to produce the vascularized network for further growth of the tumor and remote metastasis. Conclusion Rg3 inhibited the activation of microtumor vessel formation in vivo besides its apoptosis induction. Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen.
{"title":"Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis","authors":"Shen Hu, Yan Zhu, Xiangyang Xia, Xiaobo Xu, Fen Chen, X. Miao, Xinmei Chen","doi":"10.1155/2019/3815786","DOIUrl":"https://doi.org/10.1155/2019/3815786","url":null,"abstract":"Aim Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction and antiangiogenesis effect of Rg3 on orthotopic HCC in vivo. Methods The murine HCC cells Hep1-6 were implanted in the liver of mouse. With oral feeding of Rg3 (10 mg/kg once a day for 30 days), the quantitative analysis of apoptosis was performed by using pathology and a transmission electron microscope and microvessel density was quantitatively measured by immunohistochemical staining of the CD105 antibody. The mice treated with Rg3 (n = 10) were compared with the control (n = 10) using Kaplan-Meier analysis. Animal weight and tumor weight were measured to determine the toxicity of Rg3 and antitumor effect on an orthotopic HCC tumor model. Results With oral feeding of Rg3 daily in the first 30 days on tumor implantation, Rg3 significantly decreased the orthotopic tumor growth and increased the survival of animals (P < 0.05). Rg3-treated mice showed a longer survival than the control (P < 0.05). Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor apoptotic progress, which then weakened the tumor volume and its capability to produce the vascularized network for further growth of the tumor and remote metastasis. Conclusion Rg3 inhibited the activation of microtumor vessel formation in vivo besides its apoptosis induction. Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124190833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhentian Xu, Haiyang Xie, Lin Zhou, Xinhua Chen, Shusen Zheng
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but great majority of patients are already in advanced stage on the first diagnosis and lose the surgery opportunity. Multifarious image-guided interventional therapies, termed as locoregional ablations, are recommended by various HCC guidelines for the clinical practice. Transarterial chemoembolization (TACE) is firstly recommended for intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) B class) HCC but has lower necrosis rates. Radiofrequency ablation (RFA) is effective in treating HCCs smaller than 3 cm in size. Microwave ablation (MWA) can ablate larger tumor within a shorter time. Combination of TACE with RFA or MWA is effective and promising in treating larger HCC lesions but needs more clinical data to confirm its long-term outcome. The combination of TACE and RFA or MWA against hepatocellular carcinoma needs more clinical data for a better strategy. The characters and advantages of TACE, RFA, MWA, and TACE combined with RFA or MWA are reviewed to provide physician a better background on decision.
{"title":"The Combination Strategy of Transarterial Chemoembolization and Radiofrequency Ablation or Microwave Ablation against Hepatocellular Carcinoma","authors":"Zhentian Xu, Haiyang Xie, Lin Zhou, Xinhua Chen, Shusen Zheng","doi":"10.1155/2019/8619096","DOIUrl":"https://doi.org/10.1155/2019/8619096","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hepatectomy and liver transplantation (LT) are regarded as the radical treatment, but great majority of patients are already in advanced stage on the first diagnosis and lose the surgery opportunity. Multifarious image-guided interventional therapies, termed as locoregional ablations, are recommended by various HCC guidelines for the clinical practice. Transarterial chemoembolization (TACE) is firstly recommended for intermediate-stage (Barcelona Clinic Liver Cancer (BCLC) B class) HCC but has lower necrosis rates. Radiofrequency ablation (RFA) is effective in treating HCCs smaller than 3 cm in size. Microwave ablation (MWA) can ablate larger tumor within a shorter time. Combination of TACE with RFA or MWA is effective and promising in treating larger HCC lesions but needs more clinical data to confirm its long-term outcome. The combination of TACE and RFA or MWA against hepatocellular carcinoma needs more clinical data for a better strategy. The characters and advantages of TACE, RFA, MWA, and TACE combined with RFA or MWA are reviewed to provide physician a better background on decision.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"2019 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130128862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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