Pub Date : 2001-04-01DOI: 10.1097/00125480-200111000-00014
A. Vlahou, P. Schellhammer, Savvas E Mendrinos, K. Patel, F. Kondylis, L. Gong, S. Nasim, George L. Wright
Development of noninvasive methods for the diagnosis of transitional cell carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (surface enhanced laser desorption/ionization time of flight mass spectrometry) has recently been developed to facilitate protein profiling of biological mixtures. This report describes an exploratory study of this technology as a TCC diagnostic tool. Ninety-four urine samples from patients with TCC, patients with other urogenital diseases, and healthy donors were analyzed. Multiple protein changes were reproducibly detected in the TCC group, including five potential novel TCC biomarkers and seven protein clusters (mass range, 3.3 to 133 kd). One of the TCC biomarkers (3.4 kd) was also detected in bladder cancer cells procured from bladder barbotage and was identified as defensin. The TCC detection rates provided by the individual markers ranged from 43 to 70% and specificities from 70 to 86%. Combination of the protein biomarkers and clusters, increased significantly the sensitivity for detecting TCC to 87% with a specificity of 66%. Interestingly, this combinatorial approach provided sensitivity of 78% for detecting low-grade TCC compared to only 33% of voided urine or bladder-washing cytology. Collectively these results support the potential of this proteomic approach for the development of a highly sensitive urinary TCC diagnostic test.
{"title":"Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine.","authors":"A. Vlahou, P. Schellhammer, Savvas E Mendrinos, K. Patel, F. Kondylis, L. Gong, S. Nasim, George L. Wright","doi":"10.1097/00125480-200111000-00014","DOIUrl":"https://doi.org/10.1097/00125480-200111000-00014","url":null,"abstract":"Development of noninvasive methods for the diagnosis of transitional cell carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (surface enhanced laser desorption/ionization time of flight mass spectrometry) has recently been developed to facilitate protein profiling of biological mixtures. This report describes an exploratory study of this technology as a TCC diagnostic tool. Ninety-four urine samples from patients with TCC, patients with other urogenital diseases, and healthy donors were analyzed. Multiple protein changes were reproducibly detected in the TCC group, including five potential novel TCC biomarkers and seven protein clusters (mass range, 3.3 to 133 kd). One of the TCC biomarkers (3.4 kd) was also detected in bladder cancer cells procured from bladder barbotage and was identified as defensin. The TCC detection rates provided by the individual markers ranged from 43 to 70% and specificities from 70 to 86%. Combination of the protein biomarkers and clusters, increased significantly the sensitivity for detecting TCC to 87% with a specificity of 66%. Interestingly, this combinatorial approach provided sensitivity of 78% for detecting low-grade TCC compared to only 33% of voided urine or bladder-washing cytology. Collectively these results support the potential of this proteomic approach for the development of a highly sensitive urinary TCC diagnostic test.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"77 4","pages":"1491-502"},"PeriodicalIF":0.0,"publicationDate":"2001-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72484591","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 : 2000-08-01DOI: 10.1016/S0168-8278(01)81711-6
M. Bustos, B. Sangro, P. Alzuguren, A. Gil, J. Ruiz, N. Beraza, C. Qian, A. García-Pardo, J. Prieto
{"title":"Liver damage using suicide genes. A model for oval cell activation.","authors":"M. Bustos, B. Sangro, P. Alzuguren, A. Gil, J. Ruiz, N. Beraza, C. Qian, A. García-Pardo, J. Prieto","doi":"10.1016/S0168-8278(01)81711-6","DOIUrl":"https://doi.org/10.1016/S0168-8278(01)81711-6","url":null,"abstract":"","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"98 1","pages":"549-59"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86084549","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 : 2000-08-01DOI: 10.1378/CHEST.120.1_SUPPL.S34
T. Betsuyaku, Y. Fukuda, W. Parks, J. Shipley, R. Senior
Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin the two groups of mice were indistinguishable in terms of pulmonary histology and total lung collagen and elastin. However, the lungs of gelatinase B-deficient mice showed minimal alveolar bronchiolization, whereas bronchiolization was prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified immunohistochemically in terminal bronchiolar cells and bronchiolized cells 7 and 14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA was increased at the same times. Many bronchiolized cells displayed Clara cell features by electron microscopy. Some bronchiolized cells stained with antibody to helix transcription factor 4, a factor associated with the ciliated cell phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin irrespective of gelatinase B. However, gelatinase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.
{"title":"Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.","authors":"T. Betsuyaku, Y. Fukuda, W. Parks, J. Shipley, R. Senior","doi":"10.1378/CHEST.120.1_SUPPL.S34","DOIUrl":"https://doi.org/10.1378/CHEST.120.1_SUPPL.S34","url":null,"abstract":"Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin the two groups of mice were indistinguishable in terms of pulmonary histology and total lung collagen and elastin. However, the lungs of gelatinase B-deficient mice showed minimal alveolar bronchiolization, whereas bronchiolization was prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified immunohistochemically in terminal bronchiolar cells and bronchiolized cells 7 and 14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA was increased at the same times. Many bronchiolized cells displayed Clara cell features by electron microscopy. Some bronchiolized cells stained with antibody to helix transcription factor 4, a factor associated with the ciliated cell phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin irrespective of gelatinase B. However, gelatinase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"181 1","pages":"525-35"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75385206","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 : 2000-07-01DOI: 10.1016/S0021-9150(00)80289-0
H. Dietrich, Y. Hu, Y. Zou, U. Huemer, B. Metzler, C. Li, M. Mayr, Q. Xu
{"title":"Rapid development of vein graft atheroma in ApoE-deficient mice.","authors":"H. Dietrich, Y. Hu, Y. Zou, U. Huemer, B. Metzler, C. Li, M. Mayr, Q. Xu","doi":"10.1016/S0021-9150(00)80289-0","DOIUrl":"https://doi.org/10.1016/S0021-9150(00)80289-0","url":null,"abstract":"","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"427 1","pages":"659-69"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77507297","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 : 1999-05-01DOI: 10.1097/00005072-199905000-00191
D. Dickson, W. Liu, J. Hardy, M. Farrer, N. Mehta, R. Uitti, M. Mark, T. Zimmerman, L. Golbe, J. Sage, A. Sima, C. D'amato, R. Albin, S. Gilman, S. Yen
Glial cytoplasmic inclusions (GCI) are the hallmark of multiple system atrophy (MSA), a rare movement disorder frequently associated with autonomic dysfunction. In this study of 21 cases of MSA, GCI were consistently immunoreactive for alpha-synuclein and double-immunostained for ubiquitin and oligodendroglial markers, but not glial fibrillary acidic protein. No statistically significant difference was found in the density of GCI in various brain regions in the two forms of MSA, striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA). Postmortem brain samples from 9 cases of MSA were fractionated according to solubility in buffer, Triton-X 100, sodium dodecyl sulfate (SDS), and formic acid, and alpha-synuclein immunoreactivity was measured in Western blots. Total alpha-synuclein immunoreactivity was increased in MSA compared to controls, with no statistically significant difference between SND and OPCA. Most of the increase was due to alpha-synuclein in SDS fractions. In controls this fraction had little or no immunoreactivity. In 7 cases and 4 controls correlations were investigated between quantitative neuropathology and biochemical properties of alpha-synuclein. Surprisingly, the amount of SDS-soluble alpha-synuclein correlated poorly with the number of GCI in adjacent sections. Furthermore, areas with few or no GCI unexpectedly had abundant SDS-soluble alpha-synuclein. These findings provide evidence that modifications of alpha-synuclein in MSA may be more widespread than obvious histopathology. Moreover, these alterations may constitute a biochemical signature for the synucleinopathies.
{"title":"Widespread alterations of alpha-synuclein in multiple system atrophy.","authors":"D. Dickson, W. Liu, J. Hardy, M. Farrer, N. Mehta, R. Uitti, M. Mark, T. Zimmerman, L. Golbe, J. Sage, A. Sima, C. D'amato, R. Albin, S. Gilman, S. Yen","doi":"10.1097/00005072-199905000-00191","DOIUrl":"https://doi.org/10.1097/00005072-199905000-00191","url":null,"abstract":"Glial cytoplasmic inclusions (GCI) are the hallmark of multiple system atrophy (MSA), a rare movement disorder frequently associated with autonomic dysfunction. In this study of 21 cases of MSA, GCI were consistently immunoreactive for alpha-synuclein and double-immunostained for ubiquitin and oligodendroglial markers, but not glial fibrillary acidic protein. No statistically significant difference was found in the density of GCI in various brain regions in the two forms of MSA, striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA). Postmortem brain samples from 9 cases of MSA were fractionated according to solubility in buffer, Triton-X 100, sodium dodecyl sulfate (SDS), and formic acid, and alpha-synuclein immunoreactivity was measured in Western blots. Total alpha-synuclein immunoreactivity was increased in MSA compared to controls, with no statistically significant difference between SND and OPCA. Most of the increase was due to alpha-synuclein in SDS fractions. In controls this fraction had little or no immunoreactivity. In 7 cases and 4 controls correlations were investigated between quantitative neuropathology and biochemical properties of alpha-synuclein. Surprisingly, the amount of SDS-soluble alpha-synuclein correlated poorly with the number of GCI in adjacent sections. Furthermore, areas with few or no GCI unexpectedly had abundant SDS-soluble alpha-synuclein. These findings provide evidence that modifications of alpha-synuclein in MSA may be more widespread than obvious histopathology. Moreover, these alterations may constitute a biochemical signature for the synucleinopathies.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"47 1","pages":"1241-51"},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89922406","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 : 1999-05-01DOI: 10.1016/S0021-9150(99)80552-8
M. Gimbrone
{"title":"Vascular endothelium, hemodynamic forces, and atherogenesis.","authors":"M. Gimbrone","doi":"10.1016/S0021-9150(99)80552-8","DOIUrl":"https://doi.org/10.1016/S0021-9150(99)80552-8","url":null,"abstract":"","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"19 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"1999-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90676985","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 : 1999-04-01DOI: 10.1097/00005392-199904010-00470
J. J. Pizzo, A. Borkowski, S. Jacobs, N. Kyprianou
The cyclin-dependent kinase inhibitor p27(Kip1) is a powerful molecular determinant of cell cycle progression. Loss of expression of p27(Kip1) has been shown to be predictive of disease progression in several human malignancies. In this study we investigated the expression of two key cell cycle regulators, p27(Kip1) and cyclin E, in the progression of transitional cell carcinoma of the bladder. An immunohistochemical analysis was conducted in a series of 50 bladder tumor specimens, including 3 metastatic lymph nodes, and 7 normal bladder specimens, using specific antibodies against the two regulators of the cell cycle, p27(Kip1) and cyclin E. The degree of immunoreactivity was correlated with the pathological tumor grade, stage, and patient survival. A uniformly intense immunoreactivity for p27(Kip1) and cyclin E was observed in epithelial cells of normal bladder tissue. Malignant bladder tissue demonstrated a heterogeneous pattern of significantly reduced p27(Kip1) and cyclin E immunoreactivity, compared with normal urothelium (P < 0.01). In addition, there was progressive loss of expression of both cell cycle proteins with increasing tumor grade and pathological stage. Expression of p27(Kip1) was significantly lower in the poorly differentiated tumors (grades III) compared to well and moderately differentiated (grades I and II) tumors (P = 0.004). Moreover, the expression of cyclin E was lower in grade III tumors compared to grade I and II lesions, although this difference failed to reach statistical significance. Most significantly, Kaplan-Meier plots of patient survival show increased mortality risk associated with low levels of p27(Kip1) (P = 0.001) and cyclin E (P = 0.002) expression. This is the first evidence that loss of expression of p27(Kip1) and cyclin E in human bladder transitional cell carcinoma cells correlates with advancing histological aggressiveness and poor patient survival. These results have clinical importance, because they support a role for p27(Kip1) and cyclin E as novel predictive markers of the biological potential of bladder tumors that will enable identification of those tumors most likely to progress to muscle invasive disease and of patient survival.
{"title":"Loss of cell cycle regulators p27(Kip1) and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival.","authors":"J. J. Pizzo, A. Borkowski, S. Jacobs, N. Kyprianou","doi":"10.1097/00005392-199904010-00470","DOIUrl":"https://doi.org/10.1097/00005392-199904010-00470","url":null,"abstract":"The cyclin-dependent kinase inhibitor p27(Kip1) is a powerful molecular determinant of cell cycle progression. Loss of expression of p27(Kip1) has been shown to be predictive of disease progression in several human malignancies. In this study we investigated the expression of two key cell cycle regulators, p27(Kip1) and cyclin E, in the progression of transitional cell carcinoma of the bladder. An immunohistochemical analysis was conducted in a series of 50 bladder tumor specimens, including 3 metastatic lymph nodes, and 7 normal bladder specimens, using specific antibodies against the two regulators of the cell cycle, p27(Kip1) and cyclin E. The degree of immunoreactivity was correlated with the pathological tumor grade, stage, and patient survival. A uniformly intense immunoreactivity for p27(Kip1) and cyclin E was observed in epithelial cells of normal bladder tissue. Malignant bladder tissue demonstrated a heterogeneous pattern of significantly reduced p27(Kip1) and cyclin E immunoreactivity, compared with normal urothelium (P < 0.01). In addition, there was progressive loss of expression of both cell cycle proteins with increasing tumor grade and pathological stage. Expression of p27(Kip1) was significantly lower in the poorly differentiated tumors (grades III) compared to well and moderately differentiated (grades I and II) tumors (P = 0.004). Moreover, the expression of cyclin E was lower in grade III tumors compared to grade I and II lesions, although this difference failed to reach statistical significance. Most significantly, Kaplan-Meier plots of patient survival show increased mortality risk associated with low levels of p27(Kip1) (P = 0.001) and cyclin E (P = 0.002) expression. This is the first evidence that loss of expression of p27(Kip1) and cyclin E in human bladder transitional cell carcinoma cells correlates with advancing histological aggressiveness and poor patient survival. These results have clinical importance, because they support a role for p27(Kip1) and cyclin E as novel predictive markers of the biological potential of bladder tumors that will enable identification of those tumors most likely to progress to muscle invasive disease and of patient survival.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"18 1","pages":"1129-36"},"PeriodicalIF":0.0,"publicationDate":"1999-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73979237","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 : 1999-03-01DOI: 10.1097/00005392-199904010-00469
V. Aaltonen, P. Boström, K. Söderström, O. Hirvonen, J. Tuukkanen, M. Nurmi, M. Laato, J. Peltonen
The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines, RT4, 5637, and T24 (representing grades 1 to 3, respectively). Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as estimated by immunohistochemistry, the decrease being more pronounced in high-grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade 3 TCC. Immunohistochemistry and Western blotting demonstrated that TCC cell lines expressed NF1 protein at different levels, expression being almost undetectable in T24 (grade 3) cells. Northern blotting for cell lines demonstrated reduced NF1 mRNA levels in grade 3 TCC cells. Reverse transcription polymerase chain reaction for cell lines and selected grade 2 and grade 3 tissue samples demonstrated NF1 type II mRNA isoform predominance in all samples studied. Our results show that both NF1 mRNA and protein levels are decreased in high-grade TCC, suggesting that alterations of NF1 gene expression may be involved in bladder TCC carcinogenesis.
{"title":"Urinary bladder transitional cell carcinogenesis is associated with down-regulation of NF1 tumor suppressor gene in vivo and in vitro.","authors":"V. Aaltonen, P. Boström, K. Söderström, O. Hirvonen, J. Tuukkanen, M. Nurmi, M. Laato, J. Peltonen","doi":"10.1097/00005392-199904010-00469","DOIUrl":"https://doi.org/10.1097/00005392-199904010-00469","url":null,"abstract":"The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines, RT4, 5637, and T24 (representing grades 1 to 3, respectively). Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as estimated by immunohistochemistry, the decrease being more pronounced in high-grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade 3 TCC. Immunohistochemistry and Western blotting demonstrated that TCC cell lines expressed NF1 protein at different levels, expression being almost undetectable in T24 (grade 3) cells. Northern blotting for cell lines demonstrated reduced NF1 mRNA levels in grade 3 TCC cells. Reverse transcription polymerase chain reaction for cell lines and selected grade 2 and grade 3 tissue samples demonstrated NF1 type II mRNA isoform predominance in all samples studied. Our results show that both NF1 mRNA and protein levels are decreased in high-grade TCC, suggesting that alterations of NF1 gene expression may be involved in bladder TCC carcinogenesis.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"28 1","pages":"755-65"},"PeriodicalIF":0.0,"publicationDate":"1999-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82179661","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 : 1999-01-01DOI: 10.1093/gmo/9781561592630.article.j391300
Fausto
{"title":"Russell ross","authors":"Fausto","doi":"10.1093/gmo/9781561592630.article.j391300","DOIUrl":"https://doi.org/10.1093/gmo/9781561592630.article.j391300","url":null,"abstract":"","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"19 1","pages":"1309-10"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84501881","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 : 1998-10-01DOI: 10.1097/00008469-199908000-00034
C. Oliveira, R. Seruca, M. Seixas, M. Sobrinho-Simões
Gastric carcinomas with DNA replication errors (RER phenotype) display a particular clinicopathologic profile and carry a putative favorable prognosis. The RER phenotype has been identified as microsatellite instability in noncoding regions, as well as in repeat sequences within exons of several "target genes": TGFbeta RII, IGFII R, and BAX. In an attempt to find out whether the RER status is a significant prognostic factor in gastric carcinoma in a multivariate analysis and whether the clinicopathological features of the RER+ tumors are associated with mutations in the "target genes," we evaluated a series of 152 cases of sporadic gastric carcinoma. Five or six microsatellite loci and/or BAT 26, a poly(A) tract, were analyzed in each case using polymerase chain reaction and electrophoresis. Thirty-five cases (23.0%) were RER+. The RER phenotype was closely associated with a low pTNM stage and carried a significantly better prognosis. The repeat sequences of the target genes were screened for mutations in 28 RER+ and 13 RER-tumors. Mutations in TGFbeta RII occurred in 67.9% of the RER+ tumors and were significantly associated with the glandular histotype. IGFII R and BAX mutations occurred, respectively, in 25.0% and 32.1% of the cases; there was a trend toward an association between mutations in these genes and decreased nodal metastization and wall invasiveness, respectively. We conclude that the RER status is a significant prognostic indicator in gastric carcinoma and that such prognostic influence may be mediated by mutations in TGFbeta RII, IGFII R, and BAX genes.
{"title":"The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different \"target genes\": a study of the TGFbeta RII, IGFII R, and BAX genes.","authors":"C. Oliveira, R. Seruca, M. Seixas, M. Sobrinho-Simões","doi":"10.1097/00008469-199908000-00034","DOIUrl":"https://doi.org/10.1097/00008469-199908000-00034","url":null,"abstract":"Gastric carcinomas with DNA replication errors (RER phenotype) display a particular clinicopathologic profile and carry a putative favorable prognosis. The RER phenotype has been identified as microsatellite instability in noncoding regions, as well as in repeat sequences within exons of several \"target genes\": TGFbeta RII, IGFII R, and BAX. In an attempt to find out whether the RER status is a significant prognostic factor in gastric carcinoma in a multivariate analysis and whether the clinicopathological features of the RER+ tumors are associated with mutations in the \"target genes,\" we evaluated a series of 152 cases of sporadic gastric carcinoma. Five or six microsatellite loci and/or BAT 26, a poly(A) tract, were analyzed in each case using polymerase chain reaction and electrophoresis. Thirty-five cases (23.0%) were RER+. The RER phenotype was closely associated with a low pTNM stage and carried a significantly better prognosis. The repeat sequences of the target genes were screened for mutations in 28 RER+ and 13 RER-tumors. Mutations in TGFbeta RII occurred in 67.9% of the RER+ tumors and were significantly associated with the glandular histotype. IGFII R and BAX mutations occurred, respectively, in 25.0% and 32.1% of the cases; there was a trend toward an association between mutations in these genes and decreased nodal metastization and wall invasiveness, respectively. We conclude that the RER status is a significant prognostic indicator in gastric carcinoma and that such prognostic influence may be mediated by mutations in TGFbeta RII, IGFII R, and BAX genes.","PeriodicalId":77408,"journal":{"name":"The American journal of cardiovascular pathology","volume":"4 1","pages":"1211-9"},"PeriodicalIF":0.0,"publicationDate":"1998-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74328153","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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