Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460
A. A. Mohamed Adil, Lavanya Vallinayagam, K. Chitra, Shazia Jamal, A. Pandurangan, Neesar Ahmed
In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-β in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-β compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.
{"title":"Increased Expression of TGF-β and IFN-γ in Peripheral Blood Mononuclear Cells (PBMCs) Cultured in Conditioned Medium (CM) of K562 Cell Culture.","authors":"A. A. Mohamed Adil, Lavanya Vallinayagam, K. Chitra, Shazia Jamal, A. Pandurangan, Neesar Ahmed","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029460","url":null,"abstract":"In the present study, we investigated the effects of conditioned media (CM) collected from the cancer cell lines (K562, MCF-7, and HeLa) on peripheral blood mononuclear cells (PBMCs) isolated from the healthy human blood. The soluble factors in the CM are probably responsible for the differential mRNA expressions of Foxp3, Helios, Neuropilin- 1 (NRP-1), and glycoprotein A repetitions predominant (GARP), along with IFN-γ and TGF-β in PBMCs cultured with cancer cells CM. The PBMCs cultured with CM of K562 showed increased expression of Foxp3, Helios, NRP-1, GARP, IFN-γ, and TGF-β compared to PBMCs cultured with CM of MCF-7 and HeLa cells. In addition, the intracellular staining on PBMCs cultured with CM from cell lines were also evaluated for CD4, CD25, Foxp3, Helios, and NRP-1 by multicolor flow cytometry. The expression of CD4+CD25+Foxp3+, CD4+Helios+Foxp3+ and CD+NRP-1+Foxp3+ showed retarded cell population compared to control PBMCs. Our data suggest that soluble factors in CM of cancer cells may trigger the immune response in PBMCs resulting in a systematic response. Further research could lead to the identification of specific soluble factors that are involved in trafficking of cells into the immune cascades, which could be a safe and promising strategy for targeting human cancers.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"3 1","pages":"173-183"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84128326","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}
Pub Date : 2019-01-01DOI: 10.1615/JEnvironPatholToxicolOncol.2019028792
Achummantakath Hashim, Haneena Fathima, R. Muhammed, D. R. D. Neevan
Donor blood is usually screened for some risk factors, such as hepatitis, HIV, and malarial parasites, but it is not routinely screened for heavy metals although their adverse effects on the human body have been proved by a number of studies. In this study, an attempt was made to determine the effect of smoking on concentration of cadmium, nickel, and lead in donor blood. A semistructured questionnaire was prepared and given to participants. It showed that 79% (two groups: 65 smokers and 65 nonsmokers) smoked at least one cigarette per day. Collected blood samples were then subjected to atomic absorption spectrometry (AAS). In comparing blood levels between smoking and nonsmoking participants, we noted a high positive correlation between lead and nickel concentrations. There were statistically significant correlations between cadmium, lead, and nickel concentrations in the blood of smokers and nonsmokers. Moreover, because a substantial percentage of blood donors may be smokers and blood donation does not always meet demand, it would be difficult to completely exclude smokers from donating blood. Our findings indicate the need to screen for heavy metals when transfusing blood to the elderly, neonates, and infants, and to avoid transfusion of blood and blood products if levels are in the toxic range.
{"title":"Analysis of Lead, Cadmium, and Nickel in Blood Donors in Relation to Smoking-A Comparative Study.","authors":"Achummantakath Hashim, Haneena Fathima, R. Muhammed, D. R. D. Neevan","doi":"10.1615/JEnvironPatholToxicolOncol.2019028792","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2019028792","url":null,"abstract":"Donor blood is usually screened for some risk factors, such as hepatitis, HIV, and malarial parasites, but it is not routinely screened for heavy metals although their adverse effects on the human body have been proved by a number of studies. In this study, an attempt was made to determine the effect of smoking on concentration of cadmium, nickel, and lead in donor blood. A semistructured questionnaire was prepared and given to participants. It showed that 79% (two groups: 65 smokers and 65 nonsmokers) smoked at least one cigarette per day. Collected blood samples were then subjected to atomic absorption spectrometry (AAS). In comparing blood levels between smoking and nonsmoking participants, we noted a high positive correlation between lead and nickel concentrations. There were statistically significant correlations between cadmium, lead, and nickel concentrations in the blood of smokers and nonsmokers. Moreover, because a substantial percentage of blood donors may be smokers and blood donation does not always meet demand, it would be difficult to completely exclude smokers from donating blood. Our findings indicate the need to screen for heavy metals when transfusing blood to the elderly, neonates, and infants, and to avoid transfusion of blood and blood products if levels are in the toxic range.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"8 1","pages":"165-172"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84084292","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}
Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318
B. Rohini, T. Akther, M. Waseem, Jasim Khan, M. Kashif, S. Hemalatha
In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200 µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.
{"title":"AgNPs from Nigella sativa Control Breast Cancer: An In Vitro Study.","authors":"B. Rohini, T. Akther, M. Waseem, Jasim Khan, M. Kashif, S. Hemalatha","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019027318","url":null,"abstract":"In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200 µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"2060 1","pages":"185-194"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86548679","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}
Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029388
V. P. Samuel, R. Dahiya, Y. Singh, G. Gupta, S. Sah, S. K. Gubbiyappa, D. Chellappan, K. Dua
The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.
{"title":"Metformin: A Salutary Candidate for Colorectal Cancer Treatment in Patients with Diabetes.","authors":"V. P. Samuel, R. Dahiya, Y. Singh, G. Gupta, S. Sah, S. K. Gubbiyappa, D. Chellappan, K. Dua","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029388","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029388","url":null,"abstract":"The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"68 1","pages":"133-141"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85574913","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016652
C. Welz, M. Canis, S. Schwenk-Zieger, S. Becker, Vincent Stucke, F. Ihler, P. Baumeister
The popularity of electronic cigarettes (ECs) is rapidly growing and ECs are claimed to be an uncritically regarded alternative to conventional cigarettes. The mucosal tissue of the upper aerodigestive tract (UADT) is the first contact organ for xenobiotics such as liquids of ECs. The aim of this study is to investigate the bimolecular effects of e-liquids on human pharyngeal tissue cultures to evaluate whether e-liquids and their components present a risk factor for head and neck squamous cell carcinoma. Fresh tissue samples of healthy oropharyngeal mucosa were assembled into mucosal tissue cultures. Two fruit-flavored liquids (FLs), one tobacco-flavored liquid (TL) (all containing nicotine), and the corresponding base mixtures (free of nicotine and flavor) were used in three different dilutions. Cytotoxicity was assessed using the water-soluble tetrazolium-8 assay. DNA fragmentation was quantified using alkaline microgel electrophoresis. All liquids caused a significant reduction in cell viability. FLs especially showed a higher toxicity than TL. DNA fragmentation significantly increased by incubation with FL, whereas treatment with TL did not show serious DNA damage. E-liquids are cytotoxic to oropharyngeal tissue, and some liquids can induce relevant DNA damage. Thus, mutagenicity for mucosa of the UADT and e-liquids as risk factors for head and neck cancer cannot entirely be ruled out. Only the implementation of standards and regulations for liquid production and distribution can ensure a valid scientific investigation and assessment of carcinogenic potential of long-term EC use.
{"title":"Cytotoxic and Genotoxic Effects of Electronic Cigarette Liquids on Human Mucosal Tissue Cultures of the Oropharynx.","authors":"C. Welz, M. Canis, S. Schwenk-Zieger, S. Becker, Vincent Stucke, F. Ihler, P. Baumeister","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016652","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016652","url":null,"abstract":"The popularity of electronic cigarettes (ECs) is rapidly growing and ECs are claimed to be an uncritically regarded alternative to conventional cigarettes. The mucosal tissue of the upper aerodigestive tract (UADT) is the first contact organ for xenobiotics such as liquids of ECs. The aim of this study is to investigate the bimolecular effects of e-liquids on human pharyngeal tissue cultures to evaluate whether e-liquids and their components present a risk factor for head and neck squamous cell carcinoma. Fresh tissue samples of healthy oropharyngeal mucosa were assembled into mucosal tissue cultures. Two fruit-flavored liquids (FLs), one tobacco-flavored liquid (TL) (all containing nicotine), and the corresponding base mixtures (free of nicotine and flavor) were used in three different dilutions. Cytotoxicity was assessed using the water-soluble tetrazolium-8 assay. DNA fragmentation was quantified using alkaline microgel electrophoresis. All liquids caused a significant reduction in cell viability. FLs especially showed a higher toxicity than TL. DNA fragmentation significantly increased by incubation with FL, whereas treatment with TL did not show serious DNA damage. E-liquids are cytotoxic to oropharyngeal tissue, and some liquids can induce relevant DNA damage. Thus, mutagenicity for mucosa of the UADT and e-liquids as risk factors for head and neck cancer cannot entirely be ruled out. Only the implementation of standards and regulations for liquid production and distribution can ensure a valid scientific investigation and assessment of carcinogenic potential of long-term EC use.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"30 1","pages":"343-354"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75217993","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014024
A. Chattopadhyay, J. Ray
Oral submucous fibrosis (OSF) is prevalent mostly in Southeast Asia, particularly in the Indian subcontinent. Chewing betel nuts and betel leaves, with or without tobacco, has been associated with OSF. Betel quid contents including guvacine, arecoline, guvacoline, arecaidine, and chavibetol are considered to play an important part in the occurrence of OSF. Transformation of OSF to squamous cell carcinoma (SCC) is variable, but up to 13% conversion of OSF to SCC has been reported. Various genetic and molecular mechanisms impact the malignant transformation of OSF, causing changes in the cell cycle, DNA, keratinocytes, and keratin; tumor-cell proliferation and survival; angiogenesis; fibrosis through epithelial-mesenchymal transitions (EMTs), and tissue hypoxia. All are reviewed here, including potential biomarkers for malignant transformation of OSF. These interactions are not fully understood, but a critical mass of knowledge is building up to ultimately allow the understanding of all mechanisms involved.
{"title":"Molecular Pathology of Malignant Transformation of Oral Submucous Fibrosis.","authors":"A. Chattopadhyay, J. Ray","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014024","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014024","url":null,"abstract":"Oral submucous fibrosis (OSF) is prevalent mostly in Southeast Asia, particularly in the Indian subcontinent. Chewing betel nuts and betel leaves, with or without tobacco, has been associated with OSF. Betel quid contents including guvacine, arecoline, guvacoline, arecaidine, and chavibetol are considered to play an important part in the occurrence of OSF. Transformation of OSF to squamous cell carcinoma (SCC) is variable, but up to 13% conversion of OSF to SCC has been reported. Various genetic and molecular mechanisms impact the malignant transformation of OSF, causing changes in the cell cycle, DNA, keratinocytes, and keratin; tumor-cell proliferation and survival; angiogenesis; fibrosis through epithelial-mesenchymal transitions (EMTs), and tissue hypoxia. All are reviewed here, including potential biomarkers for malignant transformation of OSF. These interactions are not fully understood, but a critical mass of knowledge is building up to ultimately allow the understanding of all mechanisms involved.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"30 1","pages":"193-205"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74229568","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016387
K. Patra, Samarjit Jana, D. Mandal, S. Bhattacharjee
Accumulating evidence suggests that free radical reactions play a key part in the development of degenerative diseases and that an antioxidant-rich diet is a major defense against these free radical reactions. In this study, we explore comparative antioxidant capacities of extracts of some commonly used in Indian spices (anise, cardamom, Ceylon cinnamon, and clove) along with their purified components (anethole, eucalyptol, cinnamaldehyde, and eugenol, respectively). Eugenol shows the highest 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide scavenging and reducing power activity in terms of weight; however, this was not found when compared in terms of equivalence. Extracts of the other three spices were found to be more potent antioxidants than their corresponding active components. Interestingly, clove extract, despite possessing the highest phenol and flavonoid content, is not the most potent radical scavenger. At low concentrations, both the crude extracts and their purified components (except for anethole and eugenol) have low hemolytic activity, but at higher concentrations purified components are more toxic than their respective crude extract. This study suggests that spices as a whole are more potent antioxidants than their purified active components, perhaps reflecting the synergism among different phytochemicals present in spice extracts.
{"title":"Evaluation of the Antioxidant Activity of Extracts and Active Principles of Commonly Consumed Indian Spices.","authors":"K. Patra, Samarjit Jana, D. Mandal, S. Bhattacharjee","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016387","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016387","url":null,"abstract":"Accumulating evidence suggests that free radical reactions play a key part in the development of degenerative diseases and that an antioxidant-rich diet is a major defense against these free radical reactions. In this study, we explore comparative antioxidant capacities of extracts of some commonly used in Indian spices (anise, cardamom, Ceylon cinnamon, and clove) along with their purified components (anethole, eucalyptol, cinnamaldehyde, and eugenol, respectively). Eugenol shows the highest 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide scavenging and reducing power activity in terms of weight; however, this was not found when compared in terms of equivalence. Extracts of the other three spices were found to be more potent antioxidants than their corresponding active components. Interestingly, clove extract, despite possessing the highest phenol and flavonoid content, is not the most potent radical scavenger. At low concentrations, both the crude extracts and their purified components (except for anethole and eugenol) have low hemolytic activity, but at higher concentrations purified components are more toxic than their respective crude extract. This study suggests that spices as a whole are more potent antioxidants than their purified active components, perhaps reflecting the synergism among different phytochemicals present in spice extracts.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"110 1","pages":"299-315"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90354325","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016099
S. Şenol, A. Aydın, Duygu Kosemetin, D. Ece, I. Akalın, Hasan Abuoğlu, Esra Akdeniz Duran, D. Aydın, Burçak Erkol
Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis. The results demonstrated that ALDH1A and ARID1A may be strong independent prognostic factors associated with overall survival and recurrence-free survival (p < 0.01 and p < 0.05, respectively). Our results demonstrated that ALDH1, CD44, ARID1A, and CAIX in immunoreactive GA tumor cells exhibit different expression profiles compared with control cells and that these differences are associated with patient survival. The molecules with differential expression profiles were associated with some common functions, including hypoxia, epithelial-to-mesenchymal transition, and SW1/SNF-mediated chromatin remodeling. In addition, the loss of ALDH1, ARID1A, and CD44 and the overexpression of CAIX are important for tumor invasion and metastasis; therefore, they may serve as useful prognostic indicators of long-term survival in patients with GA. In conclusion, our study found that abnormal expression of some of the proteins evaluated in GA tumor cells might have an important role in carcinogenesis and tumor progression and thus may influence the prognosis of patients with GA.
{"title":"Gastric Adenocarcinoma Biomarker Expression Profiles and their Prognostic Value.","authors":"S. Şenol, A. Aydın, Duygu Kosemetin, D. Ece, I. Akalın, Hasan Abuoğlu, Esra Akdeniz Duran, D. Aydın, Burçak Erkol","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016099","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016099","url":null,"abstract":"Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis. The results demonstrated that ALDH1A and ARID1A may be strong independent prognostic factors associated with overall survival and recurrence-free survival (p < 0.01 and p < 0.05, respectively). Our results demonstrated that ALDH1, CD44, ARID1A, and CAIX in immunoreactive GA tumor cells exhibit different expression profiles compared with control cells and that these differences are associated with patient survival. The molecules with differential expression profiles were associated with some common functions, including hypoxia, epithelial-to-mesenchymal transition, and SW1/SNF-mediated chromatin remodeling. In addition, the loss of ALDH1, ARID1A, and CD44 and the overexpression of CAIX are important for tumor invasion and metastasis; therefore, they may serve as useful prognostic indicators of long-term survival in patients with GA. In conclusion, our study found that abnormal expression of some of the proteins evaluated in GA tumor cells might have an important role in carcinogenesis and tumor progression and thus may influence the prognosis of patients with GA.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"21 1","pages":"207-222"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80268146","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016640
R. Veena, T. Ajith, K. Janardhanan, F. Antonawich
Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.
一些研究已经开始加强辐射的抗肿瘤作用，并改善其不良影响，如减少血细胞计数和引起正常细胞的DNA损伤。在不减少血细胞计数或破坏正常细胞DNA的情况下，增强放射抗肿瘤活性的化合物可以作为放射治疗的辅助物而广泛使用。我们评估了一组特定的矿物质、维生素和氨基酸(Poly-MVA) (2 mL/kg, per os)，在有和没有辐射的情况下，对移植到实体瘤模型中的道尔顿淋巴瘤腹水(DLA)和埃利希腹水癌(EAC)细胞系的抗肿瘤作用。用60Co进行全身γ辐射暴露(2 Gy)。事先给予多聚mva可增强放射的抗肿瘤作用。此外，在4 Gy辐照后立即给予Poly-MVA，每天1次，连续2周，可保护外周血中的DNA损伤。它还可以防止辐射引起的血小板计数减少。Poly-MVA中钯-α-硫辛酸配合物独特的电子和氧化还原性质似乎是产生这种效果的原因。结果表明，Poly-MVA的抗肿瘤增强和正常细胞保护作用值得进一步研究其潜在的临床应用。
{"title":"Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.","authors":"R. Veena, T. Ajith, K. Janardhanan, F. Antonawich","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016640","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016640","url":null,"abstract":"Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"795 1","pages":"333-342"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89011693","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}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016320
C. Ozbayer, I. Degirmenci, Derya Ustuner, Guntulu Ak, F. Saydam, E. Çolak, H. Gunes, M. Metintaş
Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010). The rs318039 gene variant of miR1274 that targets DNMT3b was found to be associated with LC subtypes. When allele distributions were compared, the numbers of individuals with the C-allele were significantly lower in the NSCLC and SCLC groups. No significant associations were found for the rs72563729 variant of the miR200b gene that targets DNMT3a or for the rs145416750 variant of the miR513c gene that targets TRDMT1. The other 33 variants were found to be ancestral genotypes. Consequently, rs188912830 and rs318039 variations were associated with LC subtypes. Importantly, this study is the first to indicate the functional characterisation of miRSNPs of genes that target DNA methylation.
{"title":"miRSNPs of miR1274 and miR3202 Genes that Target MeCP2 and DNMT3b Are Associated with Lung Cancer Risk: A Study Conducted on MassARRAY Genotyping.","authors":"C. Ozbayer, I. Degirmenci, Derya Ustuner, Guntulu Ak, F. Saydam, E. Çolak, H. Gunes, M. Metintaş","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016320","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016320","url":null,"abstract":"Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010). The rs318039 gene variant of miR1274 that targets DNMT3b was found to be associated with LC subtypes. When allele distributions were compared, the numbers of individuals with the C-allele were significantly lower in the NSCLC and SCLC groups. No significant associations were found for the rs72563729 variant of the miR200b gene that targets DNMT3a or for the rs145416750 variant of the miR513c gene that targets TRDMT1. The other 33 variants were found to be ancestral genotypes. Consequently, rs188912830 and rs318039 variations were associated with LC subtypes. Importantly, this study is the first to indicate the functional characterisation of miRSNPs of genes that target DNA methylation.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"341 1","pages":"223-236"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79743135","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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