Pub Date : 2002-10-15DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I4.50
A. Natarajan
Structural and numerical chromosomal aberrations have been considered important biological end points in genotoxic studies. Conventional solid staining (such as Giemsa) has been employed to evaluate the frequencies ofinduced chromosomal aberrations following exposure to chemical or physical agents. Recently, molecular cytogenetic techniques that have become available, such as fluorescence in situ hybridization (FISH) using chromosome-specific or chromosomal regions-specific DNA libraries, have increased the resolution of detection of aberrations. The present paper reviews briefly the results obtained from basic and applied studies using the FISH technique.
{"title":"Fluorescence in situ hybridization (FISH) in genetic toxicology.","authors":"A. Natarajan","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I4.50","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V20.I4.50","url":null,"abstract":"Structural and numerical chromosomal aberrations have been considered important biological end points in genotoxic studies. Conventional solid staining (such as Giemsa) has been employed to evaluate the frequencies ofinduced chromosomal aberrations following exposure to chemical or physical agents. Recently, molecular cytogenetic techniques that have become available, such as fluorescence in situ hybridization (FISH) using chromosome-specific or chromosomal regions-specific DNA libraries, have increased the resolution of detection of aberrations. The present paper reviews briefly the results obtained from basic and applied studies using the FISH technique.","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":"293-8"},"PeriodicalIF":0.0,"publicationDate":"2002-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85506668","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 : 2002-06-29DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.90
Bandaru S. Reddy, C. Rao
During recent years, multidisciplinary studies in epidemiology and molecular biology, as well as preclinical studies, have contributed much to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. Clinical trials with NSAIDs have demonstrated that NSAID treatment caused regression of preexisting colon adenomas in patients with familial adenomatous polyposis. Preclinical efficacy studies have provided compelling evidence that several phytochemicals with antiinflammatory properties and NSAIDs act to retard, block, or reverse colon carcinogenesis. Equally exciting are opportunities for effective chemoprevention with selective cyclooxygenase-2 (COX-2) inhibitors including celecoxib and rofecoxib in a variety of preclinical models of colon cancer. Naturally occurring COX-2 inhibitors such as curcumin and certain phytosterols have been proven to be effective as chemopreventive agents against colon carcinogenesis with minimal gastrointestinal toxicity. Multistep process of carcinogenesis has provided substantial insights into the mechanisms by which naturally occurring and synthetic antiinflammatory agents modulate these events leading to suppression of tumorigenesis. Growing knowledge in this area has brought about innovative approaches using a combination of agents with different modes of action as a means of increasing efficacy and minimizing toxicity. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance would be to identify molecular targets that are critical in the growth and survival of the malignant colorectal cell and are modulated by NSAIDs and COX-2 inhibitors.
{"title":"Novel approaches for colon cancer prevention by cyclooxygenase-2 inhibitors.","authors":"Bandaru S. Reddy, C. Rao","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.90","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.90","url":null,"abstract":"During recent years, multidisciplinary studies in epidemiology and molecular biology, as well as preclinical studies, have contributed much to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. Clinical trials with NSAIDs have demonstrated that NSAID treatment caused regression of preexisting colon adenomas in patients with familial adenomatous polyposis. Preclinical efficacy studies have provided compelling evidence that several phytochemicals with antiinflammatory properties and NSAIDs act to retard, block, or reverse colon carcinogenesis. Equally exciting are opportunities for effective chemoprevention with selective cyclooxygenase-2 (COX-2) inhibitors including celecoxib and rofecoxib in a variety of preclinical models of colon cancer. Naturally occurring COX-2 inhibitors such as curcumin and certain phytosterols have been proven to be effective as chemopreventive agents against colon carcinogenesis with minimal gastrointestinal toxicity. Multistep process of carcinogenesis has provided substantial insights into the mechanisms by which naturally occurring and synthetic antiinflammatory agents modulate these events leading to suppression of tumorigenesis. Growing knowledge in this area has brought about innovative approaches using a combination of agents with different modes of action as a means of increasing efficacy and minimizing toxicity. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance would be to identify molecular targets that are critical in the growth and survival of the malignant colorectal cell and are modulated by NSAIDs and COX-2 inhibitors.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"5 1","pages":"155-64"},"PeriodicalIF":0.0,"publicationDate":"2002-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74651781","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.30
Liying Wang, D. Medan, R. Mercer, Xianglin Shi, Chuanshu Huang, V. Castranova, M. Ding, Y. Rojanasakul
Pulmonary exposure to airborne vanadium and vanadium-containing compounds is associated with acute pulmonary inflammation, characterized by a rapid influx of neutrophilic polymorphonuclear leukocytes with a peak response at 6 hours and resolution by 3 days. We hypothesized that neutrophil apoptosis is involved in the resolution of vanadium-induced lung inflammation. To test this hypothesis, mice were exposed to inspired vanadium or saline control and the bronchoalveolar lavage (BAL) cells were examined at various times for apoptosis using terminal deoxyribonucleotidyl transferase-mediated nick end labeling (TUNEL). Control mice showed only resident alveolar macrophages in the BAL with no evidence of apoptosis. In contrast, vanadium-treated mice showed clear apoptosis of BAL cells, which were predominantly neutrophils. The number of apoptotic cells gradually increased and reached a maximal level by 24 hours with subsequent decline. After 24 hours, when the vanadium-induced lung inflammation was in the resolution phase, we observed an increased number of alveolar macrophages in BAL and the engulfment of apoptotic bodies by these macrophages. At 72 hours, the total number of neutrophils in BAL fell to the baseline level, and the number of apoptotic cells was reduced. Clearance of the apoptotic product was demonstrated by the presence of apoptotic bodies in the cytoplasm of alveolar macrophages. We conclude that apoptosis of neutrophils and clearance by alveolar macrophages are important mechanisms in the resolution of vanadium-induced lung inflammation.
{"title":"Role of neutrophil apoptosis in vanadium-induced pulmonary inflammation in mice.","authors":"Liying Wang, D. Medan, R. Mercer, Xianglin Shi, Chuanshu Huang, V. Castranova, M. Ding, Y. Rojanasakul","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.30","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.30","url":null,"abstract":"Pulmonary exposure to airborne vanadium and vanadium-containing compounds is associated with acute pulmonary inflammation, characterized by a rapid influx of neutrophilic polymorphonuclear leukocytes with a peak response at 6 hours and resolution by 3 days. We hypothesized that neutrophil apoptosis is involved in the resolution of vanadium-induced lung inflammation. To test this hypothesis, mice were exposed to inspired vanadium or saline control and the bronchoalveolar lavage (BAL) cells were examined at various times for apoptosis using terminal deoxyribonucleotidyl transferase-mediated nick end labeling (TUNEL). Control mice showed only resident alveolar macrophages in the BAL with no evidence of apoptosis. In contrast, vanadium-treated mice showed clear apoptosis of BAL cells, which were predominantly neutrophils. The number of apoptotic cells gradually increased and reached a maximal level by 24 hours with subsequent decline. After 24 hours, when the vanadium-induced lung inflammation was in the resolution phase, we observed an increased number of alveolar macrophages in BAL and the engulfment of apoptotic bodies by these macrophages. At 72 hours, the total number of neutrophils in BAL fell to the baseline level, and the number of apoptotic cells was reduced. Clearance of the apoptotic product was demonstrated by the presence of apoptotic bodies in the cytoplasm of alveolar macrophages. We conclude that apoptosis of neutrophils and clearance by alveolar macrophages are important mechanisms in the resolution of vanadium-induced lung inflammation.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"28 1","pages":"343-50"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80412907","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.40
Yong Soo Lee, E. Kwon, Da-qing Jin, S. Park, Y. Kang, K. Huh, Jung-Ae Kim
Cyclooxygenases (COX) appear to be involved in the mechanism of apoptosis in various cancer cells. In this study we investigated the role of COX in the capsaicin (Cap)-induced apoptosis in SK-N-SH human neuroblastoma cells. Cap induced decreased cell viability and apoptosis in a dose-dependent manner. Cap also significantly reduced the basal generation of reactive oxygen species (ROS) and lipid peroxidation in a time-dependent fashion. Cap markedly suppressed the expression of COX-1 and COX-2. Pretreatment with NS-398, a selective COX-2 inhibitor, or indomethacin, a nonselective COX inhibitor, significantly enhanced the Cap-induced decreased cell viability and apoptosis. Exogenous application of an oxidant, H2O2, significantly prevented the Cap-induced apoptosis and suppressed the expression of COX isoforms. These results suggest that redox status-dependent regulation of COX expression may mediate apoptosis induced by Cap in human neuroblastoma cells.
{"title":"Redox status-dependent regulation of cyclooxygenases mediates the capsaicin-induced apoptosis in human neuroblastoma cells.","authors":"Yong Soo Lee, E. Kwon, Da-qing Jin, S. Park, Y. Kang, K. Huh, Jung-Ae Kim","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.40","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.40","url":null,"abstract":"Cyclooxygenases (COX) appear to be involved in the mechanism of apoptosis in various cancer cells. In this study we investigated the role of COX in the capsaicin (Cap)-induced apoptosis in SK-N-SH human neuroblastoma cells. Cap induced decreased cell viability and apoptosis in a dose-dependent manner. Cap also significantly reduced the basal generation of reactive oxygen species (ROS) and lipid peroxidation in a time-dependent fashion. Cap markedly suppressed the expression of COX-1 and COX-2. Pretreatment with NS-398, a selective COX-2 inhibitor, or indomethacin, a nonselective COX inhibitor, significantly enhanced the Cap-induced decreased cell viability and apoptosis. Exogenous application of an oxidant, H2O2, significantly prevented the Cap-induced apoptosis and suppressed the expression of COX isoforms. These results suggest that redox status-dependent regulation of COX expression may mediate apoptosis induced by Cap in human neuroblastoma cells.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"52 1","pages":"113-20"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86163782","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.130
E. Moran
It is well known that about 70% of cancer cases are due to environmental, dietary, or lifestyle factors. Accordingly, these cases maybe avoided by appropriate modifications. In addition, active chemoprevention has become a major interventional approach following the epidemiological observation of a beneficial effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in colon cancer prevention. This is chiefly due to the inhibition of the cyclooxygenase (COX) enzymes. The COX enzymatic system includes two isoenzymes, COX-1 and COX-2, that convert arachidonic acid to prostaglandins. COX-1 is constitutively expressed and synthesizes cytoprotective prostaglandins in the gastrointestinal tract. COX-2 is inducible by the oncogenes ras and scr and other cytokines; it is overexpressed in human cancer cells in which it stimulates cellular division and angiogenesis and inhibits apoptosis. NSAIDs restore apoptosis and decrease tumor mitogenesis and angiogenesis. Most cancer cells have been found to exhibit overexpression of COX-2. Epidemiological studies showed a lower risk of developing cancer of the colon, breast, esophagus, and stomach following the ingestion of NSAIDs. The use of NSAIDs in low dose was associated with a statistically significant decrease in the risk of adenomatous polyps and of overt colon cancer. The regressive effects of sulindac on foci of aberrant crypts in the colon (considered to be precursors of adenoma), and on adenocarcinoma of the colon, are of particular interest because this NSAID does not have an inhibitory effect on COX. This may support the view that the antineoplastic effect of NSAIDs may also be due to a mechanism other than COX-2 inhibition. In breast cancer, large cohort studies reported a 40 to 50% reduced risk of developing cancer, a smaller size of the primary tumor, and a reduction in the number of involved axillary lymph nodes. Similar findings have been reported in the esophagus and stomach, but not in gastric cardia adenocarcinoma. The recent development of selective COX-2 inhibitors resulted in better clinical tolerance than that associated with NSAIDs in general, with the absence of gastrointestinal side effects known to occur after the inhibition of COX-1. Encouraging results have been obtained with these new agents in familial adenomatous polyposis, colon, breast, and prostate cancer.
{"title":"Epidemiological and clinical aspects of nonsteroidal anti-inflammatory drugs and cancer risks.","authors":"E. Moran","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.130","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.130","url":null,"abstract":"It is well known that about 70% of cancer cases are due to environmental, dietary, or lifestyle factors. Accordingly, these cases maybe avoided by appropriate modifications. In addition, active chemoprevention has become a major interventional approach following the epidemiological observation of a beneficial effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in colon cancer prevention. This is chiefly due to the inhibition of the cyclooxygenase (COX) enzymes. The COX enzymatic system includes two isoenzymes, COX-1 and COX-2, that convert arachidonic acid to prostaglandins. COX-1 is constitutively expressed and synthesizes cytoprotective prostaglandins in the gastrointestinal tract. COX-2 is inducible by the oncogenes ras and scr and other cytokines; it is overexpressed in human cancer cells in which it stimulates cellular division and angiogenesis and inhibits apoptosis. NSAIDs restore apoptosis and decrease tumor mitogenesis and angiogenesis. Most cancer cells have been found to exhibit overexpression of COX-2. Epidemiological studies showed a lower risk of developing cancer of the colon, breast, esophagus, and stomach following the ingestion of NSAIDs. The use of NSAIDs in low dose was associated with a statistically significant decrease in the risk of adenomatous polyps and of overt colon cancer. The regressive effects of sulindac on foci of aberrant crypts in the colon (considered to be precursors of adenoma), and on adenocarcinoma of the colon, are of particular interest because this NSAID does not have an inhibitory effect on COX. This may support the view that the antineoplastic effect of NSAIDs may also be due to a mechanism other than COX-2 inhibition. In breast cancer, large cohort studies reported a 40 to 50% reduced risk of developing cancer, a smaller size of the primary tumor, and a reduction in the number of involved axillary lymph nodes. Similar findings have been reported in the esophagus and stomach, but not in gastric cardia adenocarcinoma. The recent development of selective COX-2 inhibitors resulted in better clinical tolerance than that associated with NSAIDs in general, with the absence of gastrointestinal side effects known to occur after the inhibition of COX-1. Encouraging results have been obtained with these new agents in familial adenomatous polyposis, colon, breast, and prostate cancer.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"29 1","pages":"193-201"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89395353","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.10
Ludmila Müller, R. Kiessling, R. Rees, G. Pawelec
Evidence that tumors are immunogenic continues to accumulate. Although they frequently do express antigens in a form recognizable by the host immune system, tumors commonly "escape" the immune response. Tumors may therefore progress by evolving variants that can evade immune responses or by developing other strategies to avoid immune control. The purpose of this review is to consider the current status of knowledge concerning these different tumor-escape strategies, in the form of an update of previous publications in this journal.
{"title":"Escape mechanisms in tumor immunity: an update.","authors":"Ludmila Müller, R. Kiessling, R. Rees, G. Pawelec","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.10","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I4.10","url":null,"abstract":"Evidence that tumors are immunogenic continues to accumulate. Although they frequently do express antigens in a form recognizable by the host immune system, tumors commonly \"escape\" the immune response. Tumors may therefore progress by evolving variants that can evade immune responses or by developing other strategies to avoid immune control. The purpose of this review is to consider the current status of knowledge concerning these different tumor-escape strategies, in the form of an update of previous publications in this journal.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"13 1","pages":"277-330"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82076910","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I1.30
K. Kaur, Saroj Arora, Subodh Kumar, A. Nagpal
We determined the antimutagenicity of phenolic fractions of Terminalia arjuna (soluble and insoluble in chloroform) against two direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and sodium azide, and against the S9-dependent mutagen 2-aminofluorene (2AF), in TA98 and TA100 tester strains of Salmonella typhimurium. We found that the phenolic fractions of T. arjuna inhibited revertants induced by the S9-dependent mutagen more remarkably than the direct-acting mutagens. Furthermore, the phenolic fractions showed maximum inhibition of 98% and 101.55%, respectively, in the pre-incubation mode of treatment against the mutations induced by 2AF. Overall, the fractions inhibited the revertants induced by S9-dependent mutagens more effectively than those induced by direct-acting mutagens. The percentage of inhibition was higher in the pre-incubation than with direct acting mutagens. The fraction insoluble in chloroform showed more inhibition than the soluble one, which corresponds to a higher polyphenol content in the insoluble fraction than in the soluble extract.
{"title":"Modulatory effect of phenolic fractions of Terminalia arjuna on the mutagenicity in Ames assay.","authors":"K. Kaur, Saroj Arora, Subodh Kumar, A. Nagpal","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I1.30","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I1.30","url":null,"abstract":"We determined the antimutagenicity of phenolic fractions of Terminalia arjuna (soluble and insoluble in chloroform) against two direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and sodium azide, and against the S9-dependent mutagen 2-aminofluorene (2AF), in TA98 and TA100 tester strains of Salmonella typhimurium. We found that the phenolic fractions of T. arjuna inhibited revertants induced by the S9-dependent mutagen more remarkably than the direct-acting mutagens. Furthermore, the phenolic fractions showed maximum inhibition of 98% and 101.55%, respectively, in the pre-incubation mode of treatment against the mutations induced by 2AF. Overall, the fractions inhibited the revertants induced by S9-dependent mutagens more effectively than those induced by direct-acting mutagens. The percentage of inhibition was higher in the pre-incubation than with direct acting mutagens. The fraction insoluble in chloroform showed more inhibition than the soluble one, which corresponds to a higher polyphenol content in the insoluble fraction than in the soluble extract.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"48 1","pages":"45-56"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80215453","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.110
Takashi Takahashi, K. Kozaki, Y. Yatabe, H. Achiwa, T. Hida
It is well accepted that an increase in the expression of cyclooxygenase-2 (COX-2), a key inducible enzyme involved in the production of prostaglandins and other eicosanoids, may play a significant role in carcinogenesis in addition to its well-known role in inflammatory reactions. Whereas previous studies were largely confined to colorectal tumorigenesis, we have shown that a significantly increased expression of COX-2 may also play a role in the development of lung cancer. COX-2 expression was found to be frequently elevated in lung cancer, especially in adenocarcinoma, and the proportion of lung cancer cells with marked COX-2 expression was much higher in lymph node metastases than in the corresponding primary tumors. It was also shown that early stage adenocarcinoma patients with increased COX-2 expression who were surgically treated had a shorter survival. Our studies, which used high- and low-metastatic human lung cancer cell sublines established in our laboratory, revealed an association between metastatic capabilities and COX-2 expression levels: COX-2-specific inhibitors could inhibit in vitro the invasion of the highly metastatic NCI-H460-LNM35 clone through Matrigel-containing basement membrane components as well as the spontaneous in vivo metastasis in SCID mice. Taken together, these findings suggest that an increase in COX-2 expression maybe associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype.
{"title":"Increased expression of COX-2 in the development of human lung cancers.","authors":"Takashi Takahashi, K. Kozaki, Y. Yatabe, H. Achiwa, T. Hida","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.110","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I2.110","url":null,"abstract":"It is well accepted that an increase in the expression of cyclooxygenase-2 (COX-2), a key inducible enzyme involved in the production of prostaglandins and other eicosanoids, may play a significant role in carcinogenesis in addition to its well-known role in inflammatory reactions. Whereas previous studies were largely confined to colorectal tumorigenesis, we have shown that a significantly increased expression of COX-2 may also play a role in the development of lung cancer. COX-2 expression was found to be frequently elevated in lung cancer, especially in adenocarcinoma, and the proportion of lung cancer cells with marked COX-2 expression was much higher in lymph node metastases than in the corresponding primary tumors. It was also shown that early stage adenocarcinoma patients with increased COX-2 expression who were surgically treated had a shorter survival. Our studies, which used high- and low-metastatic human lung cancer cell sublines established in our laboratory, revealed an association between metastatic capabilities and COX-2 expression levels: COX-2-specific inhibitors could inhibit in vitro the invasion of the highly metastatic NCI-H460-LNM35 clone through Matrigel-containing basement membrane components as well as the spontaneous in vivo metastasis in SCID mice. Taken together, these findings suggest that an increase in COX-2 expression maybe associated with the development of lung cancer and possibly with the acquisition of an invasive and metastatic phenotype.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"0602 1","pages":"177-81"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83024706","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I3.20
Jasbir Singh, Kovleen, H. M. Dani, Rajeshwar Sharmar
Chemical carcinogens are organ selective and not organ specific. Microsomal degranulation elution profiles employing sepharose CL-2B gel filtration for the separation of microsomes from different organs of rats before and after treatment with some known chemical carcinogens have shown for the first time that carcinogens selectively detach maximum ribosomes from rough reticular membranes of their target organs. The detachment of ribosomes from other organs varies, but is comparatively lesser than that in the target organs. A chemical carcinogen might, therefore, be tumorigenic for several organs, possibly depending on the dose reaching a particular organ and its activation to the ultimate form of the carcinogen.
{"title":"Organ selectivity of chemical carcinogens.","authors":"Jasbir Singh, Kovleen, H. M. Dani, Rajeshwar Sharmar","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I3.20","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I3.20","url":null,"abstract":"Chemical carcinogens are organ selective and not organ specific. Microsomal degranulation elution profiles employing sepharose CL-2B gel filtration for the separation of microsomes from different organs of rats before and after treatment with some known chemical carcinogens have shown for the first time that carcinogens selectively detach maximum ribosomes from rough reticular membranes of their target organs. The detachment of ribosomes from other organs varies, but is comparatively lesser than that in the target organs. A chemical carcinogen might, therefore, be tumorigenic for several organs, possibly depending on the dose reaching a particular organ and its activation to the ultimate form of the carcinogen.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"15 1","pages":"213-21"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75353633","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 : 2002-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.V21.I1.50
P. Gajalakshmi, P. Mallick, P. Venkatesan, S. T. Santhiya, A. Ramesh
In a comparative study of sister chromatid exchanges (SCEs) in cultured lymphocytes, we evaluated the genotoxic risk in 104 male spray painters employed in repair workshops in Chennai City, India, and 50 matched healthy, unexposed controls. We found a higher frequency of SCEs among painters (3.74 +/- 0.11, mean +/- SE) than among controls (2.15 +/- 0.08), and among smoking painters (4.03 +/- 0.21) than among nonsmoking painters (3.55 +/- 0.13), with no significant difference in controls (smokers: 2.1 +/- 0.2; nonsmokers: 2.2 +/- 0.1). Alcoholism did not contribute to an increased SCE frequency. Stepwise multiple linear regression analysis on painters showed that duration of service, smoking, and alcoholism significantly affected SCE scores and explained the 14% variation observed.
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