The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Walter N. Hittelman - One of the best experts on this subject based on the ideXlab platform.
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cervical Chromosome 9 polysomy validation and use as a surrogate endpoint biomarker in a 4 hpr chemoprevention trial
Gynecologic Oncology, 2005Co-Authors: Heung Gon Kim, Walter N. Hittelman, Jose-miguel Yamal, Iouri Boiko, Adriana Linares, Anne-therese Vlastos, Anais Malpica, Neely E Atkinson, Michele FollenAbstract:Abstract Background. Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in Chromosome number, Chromosome translocations, and gene amplifications. This report focuses on establishing Chromosome 9 polysomy as a cervical biomarker of Chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. Methods. We used 37 cervical cone specimens to validate Chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. Results. The Cell Index, the ratio of the number of total Chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, Chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Conclusions. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the Chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.
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Cervical Chromosome 9 polysomy: validation and use as a surrogate endpoint biomarker in a 4-HPR chemoprevention trial.
Gynecologic oncology, 2005Co-Authors: Heung Gon Kim, Jose-miguel Yamal, Iouri Boiko, Adriana Linares, Anne-therese Vlastos, E Neely Atkinson, Anais Malpica, Walter N. HittelmanAbstract:Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in Chromosome number, Chromosome translocations, and gene amplifications. This report focuses on establishing Chromosome 9 polysomy as a cervical biomarker of Chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. We used 37 cervical cone specimens to validate Chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. The Cell Index, the ratio of the number of total Chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, Chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the Chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.
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P53 expression and polysomies of Chromosome 9, 17 in head and neck cancer prognosis.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 1999Co-Authors: Navapun Charuruks, Narin Voravud, Waun Ki Hong, Dong M. Shin, Walter N. HittelmanAbstract:Sixty-nine cases of head and neck squamous cell carcinoma were examined by immunohistochemistry for p53 and Chromosome in situ hybridization for Chromosome 9 and 17 to determine the relationship between p53 expression and polysomies of Chromosome 9 and 17 with the development of a second primary tumor as well as recurrence of primary tumor of head and neck squamous cell carcinoma. We found early expression of p53 in the normal and premaligant lesions adjacent to tumor which was associated with a gradual increase in the fraction of positive nuclei as well as numbers of cancer. We also found statistically significant increments of polysomies of Chromosome 9 and 17 in terms of the polysomy index seen through the histologic changes occurring during multistep tumorigenesis. Our results could not demonstrate statistically significant correlation between p53 expression and PI 9 and 17 in tumorigenesis. Interestingly, however, there was a strong correlation between p53 expression and second primary tumor as well as recurrence of primary tumor. The p53 expressed group had a seven fold increased incidence in developing second primary tumor and a two and a half times increased incidence for recurrence of primary tumor, compared to the non-expressed group. We conclude that p53 expression and polysomies of Chromosome 9 and 17 have an important role in multistep tumorigenesis in HNSCC. There was no significant correlation between p53 expression and polysomies of Chromosome 9 and 17. However, the expression of p53 was statistically significant for association with second primary tumor and recurrence of primary tumor of head and neck squamous cell carcinoma.
David Sidransky - One of the best experts on this subject based on the ideXlab platform.
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localization of tumor suppressor loci on Chromosome 9 in primary human renal cell carcinomas
Cancer Research, 1995Co-Authors: Paul Cairns, Kaori Tokino, Yolanda Eby, David SidranskyAbstract:To investigate the potential loss of tumor suppressor gene loci on Chromosome 9 in human renal cell tumorigenesis we analyzed 42 paired normal and tumor DNAs with 18 polymorphic microsatellite markers spanning this Chromosome. Fourteen of 42 (33%) tumors showed partial or complete deletion of Chromosome 9. Deletion mapping provided evidence for the presence of a suppressor locus on both the short and long arm of Chromosome 9. Homozygous deletion at 9p21–22 in one renal tumor and a selective deletion of distal 9q in another tumor localized the critical regions. The CDKN2/p16 gene was further investigated as a candidate suppressor locus on 9p21–22 by multiplex PCR, Southern analysis, and exon sequencing. We found no additional cases of homozygous deletion nor any rearrangements or point mutations of CDKN2/p16 . This is the first report of 9p loss of heterozygosity, homozygous deletion of 9p21–22 and selective deletion of 9q in primary renal cell carcinomas. Understanding the molecular genetic basis of renal cell progression will require the isolation and characterization of additional tumor suppressor genes on Chromosome 9.
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frequent loss of Chromosome 9 in human primary non small cell lung cancer
Cancer Research, 1994Co-Authors: Adrian Merlo, Edward Gabrielson, Frederic B Askin, David SidranskyAbstract:Abstract We analyzed the pattern of allelic loss on Chromosome 9 in 40 primary human non-small cell lung cancers including 16 squamous cell, 18 adeno-, and 6 large cell carcinomas. Using 24 polymorphic microsatellite markers spanning Chromosome 9, we found that 27 of 40 (67.5%) of these neoplasms displayed loss of heterozygosity (LOH) on Chromosome 9. Most tumors showed LOH for all informative markers on both chromosomal arms, whereas five tumors demonstrated partial LOH on Chromosome 9. In four of these tumors, allelic loss was limited to the 9p arm, whereas in the remaining specimen, LOH extended from 9p21–22 to terminal 9q. These five tumors delineate a minimal area of loss at 9p21–22, which includes a previously defined tumor suppressor gene locus. We have identified a distinct region of loss on Chromosome 9p commonly involved in non-small cell lung cancer tumorigenesis.
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evidence for two bladder cancer suppressor loci on human Chromosome 9
Cancer Research, 1993Co-Authors: J M Ruppert, Kaori Tokino, David SidranskyAbstract:Most carcinomas of the bladder show loss of heterozygosity for markers on human Chromosome 9, which suggests that one or more tumor suppressor genes are located on this Chromosome. Several observations suggest that such alterations are an important early step in tumorigenesis. We analyzed the pattern of allelic loss in 46 primary carcinomas of the bladder using 19 polymorphic markers from Chromosome 9. While most tumors with allelic loss showed loss of heterozygosity for all informative markers that were tested, six tumors demonstrated only partial loss of Chromosome 9. Two tumors with partial loss contained deletions that predominantly involved the q arm, as shown by previous studies. The other four tumors contained deletions that predominantly or exclusively involved the p arm, with a common region of loss between D9S161 (9p21) and the telomere. The results show that there is no single common region of loss on Chromosome 9 and identify two distinct regions of loss that may contain bladder tumor suppressor loci.
Shinichiro Nanko - One of the best experts on this subject based on the ideXlab platform.
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FAMILIAL SCHIZOPHRENIA WITH PERICENTRIC INVERSION OF Chromosome 9: A CASE REPORT
Schizophrenia research, 1998Co-Authors: Kyu Bak Lee, Hiroshi Kunugi, Shinichiro NankoAbstract:We report a case with schizophrenia who had a pericentric inversion of Chromosome 9 (inv. 9) and whose mother has the same illness and karyotype. Although inv. 9 has been considered to be a common chromosomal rearrangement without specific phenotype, recent evidence has shown that there are several different forms of inv. 9 with differential breakpoints. This indicates that phenotypes of inv. 9 may vary depending on the location of breakpoints. Thus our cases may be valuable material to localize breakpoints on Chromosome 9, which may lead to cloning of a susceptibility gene for schizophrenia.
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Pericentric Region of Chromosome 9 is a Possible Candidate Region for Linkage Study of Schizophrenia
Biological Psychiatry, 1993Co-Authors: Shinichiro Nanko, Hiroshi Kunugi, T. Sasaki, Rimmei Fukuda, Tsuneta Kawate, Hajime KazamatsuriAbstract:We have undertaken a systematic G-banding survey to find structural chromosomal abnormalities among patients with schizophrenia. Of 120 patients with DSM-III-R schizophrenia, four (3.3%) had a pericentric inversion of Chromosome 9 and three (2.5%) had a X/XX mosaicism. The frequency of pericentric inversion of Chromosome 9 among patients with schizophrenia was statistically higher than those among newborns and Asian populations. Our results indicate that the pericentric region of Chromosome 9 might be one of the potential regions of interest for linkage analysis of schizophrenia.
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Schizophrenia with pericentric inversion of Chromosome 9: a case report.
The Japanese journal of psychiatry and neurology, 1993Co-Authors: Shinichiro NankoAbstract:: A case of schizophrenia according to the DSM-III-R criteria with pericentric inversion of Chromosome 9 was reported. This case and the review of the literature indicate that the pericentric region of Chromosome 9 might be one of the potential regions of interest for linkage analysis of psychiatric disorders.
Heung Gon Kim - One of the best experts on this subject based on the ideXlab platform.
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cervical Chromosome 9 polysomy validation and use as a surrogate endpoint biomarker in a 4 hpr chemoprevention trial
Gynecologic Oncology, 2005Co-Authors: Heung Gon Kim, Walter N. Hittelman, Jose-miguel Yamal, Iouri Boiko, Adriana Linares, Anne-therese Vlastos, Anais Malpica, Neely E Atkinson, Michele FollenAbstract:Abstract Background. Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in Chromosome number, Chromosome translocations, and gene amplifications. This report focuses on establishing Chromosome 9 polysomy as a cervical biomarker of Chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. Methods. We used 37 cervical cone specimens to validate Chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. Results. The Cell Index, the ratio of the number of total Chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, Chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Conclusions. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the Chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.
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Cervical Chromosome 9 polysomy: validation and use as a surrogate endpoint biomarker in a 4-HPR chemoprevention trial.
Gynecologic oncology, 2005Co-Authors: Heung Gon Kim, Jose-miguel Yamal, Iouri Boiko, Adriana Linares, Anne-therese Vlastos, E Neely Atkinson, Anais Malpica, Walter N. HittelmanAbstract:Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in Chromosome number, Chromosome translocations, and gene amplifications. This report focuses on establishing Chromosome 9 polysomy as a cervical biomarker of Chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. We used 37 cervical cone specimens to validate Chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. The Cell Index, the ratio of the number of total Chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, Chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the Chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.
Michele Follen - One of the best experts on this subject based on the ideXlab platform.
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cervical Chromosome 9 polysomy validation and use as a surrogate endpoint biomarker in a 4 hpr chemoprevention trial
Gynecologic Oncology, 2005Co-Authors: Heung Gon Kim, Walter N. Hittelman, Jose-miguel Yamal, Iouri Boiko, Adriana Linares, Anne-therese Vlastos, Anais Malpica, Neely E Atkinson, Michele FollenAbstract:Abstract Background. Several genetic alterations have been described in cervical cancers including: human papillomavirus (HPV) E6 and E7 oncoproteins, subtle sequence changes, alterations in Chromosome number, Chromosome translocations, and gene amplifications. This report focuses on establishing Chromosome 9 polysomy as a cervical biomarker of Chromosome instability and using it in a chemoprevention trial. Chromosomal instability is a feature of most human cancers and is probably an early event in the process. Methods. We used 37 cervical cone specimens to validate Chromosome 9 polysomy as a biomarker and then tested its modulation in a randomized clinical trial of 4-hydroxyphenylretinamide (4-HPR) in 39 patients with three blinded histopathologic reviews. No confounders were identified. In the present study, immunohistocytochemical analysis of Chromosome 9 polysomy was carried out and quantitatively measured. Results. The Cell Index, the ratio of the number of total Chromosome 9 copies to the total number of ells, increases significantly in archival samples as the cervix changes from normal to CIN to invasive cancer. In the chemoprevention trial, Chromosome 9 polysomy was used as a biomarker and supported the histological analysis showing that 4-HPR impaired the natural regression response. Conclusions. Chromosome 9 polysomy appears to be a marker of genetic instability that can be used in chemoprevention trials as a surrogate endpoint biomarker. In this randomized trial of 4-HPR, the Chromosome 9 polysomy measurements supported the clinical histopathologic reading in a quantitative manner suggesting that 4-HPR at 200 mg/day may have been inhibiting the regression seen in the placebo arm by inducing genetic instability.