The Experts below are selected from a list of 36 Experts worldwide ranked by ideXlab platform
William B. Coleman - One of the best experts on this subject based on the ideXlab platform.
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Molecular discrimination of multiple primary versus metastatic cancers of the lung and head and neck
Cancer Research, 2007Co-Authors: Robyn R. Mercer, Natalie C. Lucas, Dani Zander, Gregory J. Tsongalis, William B. ColemanAbstract:140 Exposure of the epithelium of the aerodigestive and respiratory tracts to cigarette smoke results in cancers of the lung and head and neck (H/N) region. Patients with cancers of the H/N are at a high risk of developing subsequent Tumors in the lungs, often characterized as metastatic lesions, even though they present as a solitary mass in the majority of cases. The distinction between a metastatic lesion and new primary Tumor is difficult when the Tumors are of the same histologic type. Thus, molecular methods are needed to discriminate Tumor lineage and relatedness (metastasis versus multiple primary Tumors). The goal of our study was to refine a method to analyze multiple Tumors that does not rely on collection of normal tissue and can be performed with minimal Tumor sample. Genomic DNA was collected from 5 patients that presented with squamous cell carcinoma in both the lung and H/N (2-3 Tumors per patient) and analyzed using a PCR-based approach to assay for allelic loss. Allelic loss of a single marker in Tumor 1 plus allelic loss of a separate marker residing on a different chromosome in Tumor 2 was defined as a mutually exclusive allelic loss (MEAL). Analysis of a subset of Tumors revealed that intra-Tumor heterogeneity resulted in approximately 5% allelic variation (1 out of 20 markers). Therefore, Tumor pairs that contained two or more MEALs were categorized as highly probable independent primary Tumors. We concluded that 3 of the 5 patients had multiple primary Tumors. Clinically, 2 of these 3 cases would have been classified as metastases due to the short interval between Tumor onset (26 and 19 months). The third patient presented with a lung Tumor, followed 3.5 years by two simultaneous, distinct Tumors of the Pharynx. Tumor relatedness would have been questioned clinically for the H/N Tumors, although molecular analysis clearly classified all three Tumors as multiple primary lesions. The results of this study demonstrate that molecular methods can distinguish multiple primary squamous cell carcinomas involving the lung and H/N regions. This method is rapid, sensitive, does not rely on normal tissue for analysis, and is amenable to the analysis of DNA from archived Tumor specimens. R.R.M. is supported by a training grant from the National Institutes of Environmental Health Sciences, T32 ES017017. This research is supported by a grant from the National Institutes of Health, CA 78343.
Wolfgang Zacharias - One of the best experts on this subject based on the ideXlab platform.
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Upregulation of cystatin M during the progression of oropharyngeal squamous cell carcinoma from primary Tumor to metastasis.
Oral oncology, 2003Co-Authors: Nadarajah Vigneswaran, Wolfgang ZachariasAbstract:Abstract To identify metastasis-associated molecules in oropharyngeal squamous cell carcinomas (OSCC), we recently compared mRNA expression profiles of cell lines derived from primary and metastatic lesions of OSCC using microarray technology. Cystatin M, an endogenous cathepsin B inhibitor, was expressed 40-fold higher in the metastatic versus the primary Tumor cell line. To show that different cystatin expression levels affect the cell lines’ sensitivities to TNF-induced apoptosis by differentially regulating cathepsin B activity. The 686Tu and 686Ln cell lines were established from a 49-year-old male patient with an OSCC involving the posterior tongue and oro-Pharynx (Tumor stage T 3 N 3B ). RT-PCR, Western blots, immunohistochemistry, and in situ hybridization all confirmed increased cystatin M expression in 686Ln compared to 686Tu cells, and in the parent archival Tumors. TNF-α induced apoptosis was easily detected in 686Tu, but only marginally in 686Ln cells. Thus, we propose that elevated cystatin M expression aids metastasis by blocking intrinsic cathepsin B activity and rescuing Tumor cells from TNF-induced apoptosis.
Robyn R. Mercer - One of the best experts on this subject based on the ideXlab platform.
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Molecular discrimination of multiple primary versus metastatic cancers of the lung and head and neck
Cancer Research, 2007Co-Authors: Robyn R. Mercer, Natalie C. Lucas, Dani Zander, Gregory J. Tsongalis, William B. ColemanAbstract:140 Exposure of the epithelium of the aerodigestive and respiratory tracts to cigarette smoke results in cancers of the lung and head and neck (H/N) region. Patients with cancers of the H/N are at a high risk of developing subsequent Tumors in the lungs, often characterized as metastatic lesions, even though they present as a solitary mass in the majority of cases. The distinction between a metastatic lesion and new primary Tumor is difficult when the Tumors are of the same histologic type. Thus, molecular methods are needed to discriminate Tumor lineage and relatedness (metastasis versus multiple primary Tumors). The goal of our study was to refine a method to analyze multiple Tumors that does not rely on collection of normal tissue and can be performed with minimal Tumor sample. Genomic DNA was collected from 5 patients that presented with squamous cell carcinoma in both the lung and H/N (2-3 Tumors per patient) and analyzed using a PCR-based approach to assay for allelic loss. Allelic loss of a single marker in Tumor 1 plus allelic loss of a separate marker residing on a different chromosome in Tumor 2 was defined as a mutually exclusive allelic loss (MEAL). Analysis of a subset of Tumors revealed that intra-Tumor heterogeneity resulted in approximately 5% allelic variation (1 out of 20 markers). Therefore, Tumor pairs that contained two or more MEALs were categorized as highly probable independent primary Tumors. We concluded that 3 of the 5 patients had multiple primary Tumors. Clinically, 2 of these 3 cases would have been classified as metastases due to the short interval between Tumor onset (26 and 19 months). The third patient presented with a lung Tumor, followed 3.5 years by two simultaneous, distinct Tumors of the Pharynx. Tumor relatedness would have been questioned clinically for the H/N Tumors, although molecular analysis clearly classified all three Tumors as multiple primary lesions. The results of this study demonstrate that molecular methods can distinguish multiple primary squamous cell carcinomas involving the lung and H/N regions. This method is rapid, sensitive, does not rely on normal tissue for analysis, and is amenable to the analysis of DNA from archived Tumor specimens. R.R.M. is supported by a training grant from the National Institutes of Environmental Health Sciences, T32 ES017017. This research is supported by a grant from the National Institutes of Health, CA 78343.
Nadarajah Vigneswaran - One of the best experts on this subject based on the ideXlab platform.
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Upregulation of cystatin M during the progression of oropharyngeal squamous cell carcinoma from primary Tumor to metastasis.
Oral oncology, 2003Co-Authors: Nadarajah Vigneswaran, Wolfgang ZachariasAbstract:Abstract To identify metastasis-associated molecules in oropharyngeal squamous cell carcinomas (OSCC), we recently compared mRNA expression profiles of cell lines derived from primary and metastatic lesions of OSCC using microarray technology. Cystatin M, an endogenous cathepsin B inhibitor, was expressed 40-fold higher in the metastatic versus the primary Tumor cell line. To show that different cystatin expression levels affect the cell lines’ sensitivities to TNF-induced apoptosis by differentially regulating cathepsin B activity. The 686Tu and 686Ln cell lines were established from a 49-year-old male patient with an OSCC involving the posterior tongue and oro-Pharynx (Tumor stage T 3 N 3B ). RT-PCR, Western blots, immunohistochemistry, and in situ hybridization all confirmed increased cystatin M expression in 686Ln compared to 686Tu cells, and in the parent archival Tumors. TNF-α induced apoptosis was easily detected in 686Tu, but only marginally in 686Ln cells. Thus, we propose that elevated cystatin M expression aids metastasis by blocking intrinsic cathepsin B activity and rescuing Tumor cells from TNF-induced apoptosis.
Gregory J. Tsongalis - One of the best experts on this subject based on the ideXlab platform.
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Molecular discrimination of multiple primary versus metastatic cancers of the lung and head and neck
Cancer Research, 2007Co-Authors: Robyn R. Mercer, Natalie C. Lucas, Dani Zander, Gregory J. Tsongalis, William B. ColemanAbstract:140 Exposure of the epithelium of the aerodigestive and respiratory tracts to cigarette smoke results in cancers of the lung and head and neck (H/N) region. Patients with cancers of the H/N are at a high risk of developing subsequent Tumors in the lungs, often characterized as metastatic lesions, even though they present as a solitary mass in the majority of cases. The distinction between a metastatic lesion and new primary Tumor is difficult when the Tumors are of the same histologic type. Thus, molecular methods are needed to discriminate Tumor lineage and relatedness (metastasis versus multiple primary Tumors). The goal of our study was to refine a method to analyze multiple Tumors that does not rely on collection of normal tissue and can be performed with minimal Tumor sample. Genomic DNA was collected from 5 patients that presented with squamous cell carcinoma in both the lung and H/N (2-3 Tumors per patient) and analyzed using a PCR-based approach to assay for allelic loss. Allelic loss of a single marker in Tumor 1 plus allelic loss of a separate marker residing on a different chromosome in Tumor 2 was defined as a mutually exclusive allelic loss (MEAL). Analysis of a subset of Tumors revealed that intra-Tumor heterogeneity resulted in approximately 5% allelic variation (1 out of 20 markers). Therefore, Tumor pairs that contained two or more MEALs were categorized as highly probable independent primary Tumors. We concluded that 3 of the 5 patients had multiple primary Tumors. Clinically, 2 of these 3 cases would have been classified as metastases due to the short interval between Tumor onset (26 and 19 months). The third patient presented with a lung Tumor, followed 3.5 years by two simultaneous, distinct Tumors of the Pharynx. Tumor relatedness would have been questioned clinically for the H/N Tumors, although molecular analysis clearly classified all three Tumors as multiple primary lesions. The results of this study demonstrate that molecular methods can distinguish multiple primary squamous cell carcinomas involving the lung and H/N regions. This method is rapid, sensitive, does not rely on normal tissue for analysis, and is amenable to the analysis of DNA from archived Tumor specimens. R.R.M. is supported by a training grant from the National Institutes of Environmental Health Sciences, T32 ES017017. This research is supported by a grant from the National Institutes of Health, CA 78343.