The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Angelo M De Marzo - One of the best experts on this subject based on the ideXlab platform.

  • decreased nkx3 1 protein expression in focal prostatic atrophy prostatic intraepithelial neoplasia and adenocarcinoma association with gleason score and Chromosome 8p deletion
    Cancer Research, 2006
    Co-Authors: Carlise R Bethel, Dennis A Faith, Xiang Li, Bin Guan, Jessica Hicks, Robert B Jenkins, Charles J Bieberich, Angelo M De Marzo
    Abstract:

    NKX3.1 is a homeobox gene located at Chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 ( C-MYC ) and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on Chromosome 8p are associated with more advanced invasive and aggressive disease. (Cancer Res 2006; 66(22): 10683-90)

  • decreased nkx3 1 protein expression in focal prostatic atrophy prostatic intraepithelial neoplasia and adenocarcinoma association with gleason score and Chromosome 8p deletion
    Cancer Research, 2006
    Co-Authors: Carlise R Bethel, Dennis A Faith, Bin Guan, Jessica Hicks, Robert B Jenkins, Charles J Bieberich, Fusheng Lan, Angelo M De Marzo
    Abstract:

    NKX3.1 is a homeobox gene located at Chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 (C-MYC) and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on Chromosome 8p are associated with more advanced invasive and aggressive disease.

Carlise R Bethel - One of the best experts on this subject based on the ideXlab platform.

  • decreased nkx3 1 protein expression in focal prostatic atrophy prostatic intraepithelial neoplasia and adenocarcinoma association with gleason score and Chromosome 8p deletion
    Cancer Research, 2006
    Co-Authors: Carlise R Bethel, Dennis A Faith, Xiang Li, Bin Guan, Jessica Hicks, Robert B Jenkins, Charles J Bieberich, Angelo M De Marzo
    Abstract:

    NKX3.1 is a homeobox gene located at Chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 ( C-MYC ) and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on Chromosome 8p are associated with more advanced invasive and aggressive disease. (Cancer Res 2006; 66(22): 10683-90)

  • decreased nkx3 1 protein expression in focal prostatic atrophy prostatic intraepithelial neoplasia and adenocarcinoma association with gleason score and Chromosome 8p deletion
    Cancer Research, 2006
    Co-Authors: Carlise R Bethel, Dennis A Faith, Bin Guan, Jessica Hicks, Robert B Jenkins, Charles J Bieberich, Fusheng Lan, Angelo M De Marzo
    Abstract:

    NKX3.1 is a homeobox gene located at Chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 (C-MYC) and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in five of seven cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on Chromosome 8p are associated with more advanced invasive and aggressive disease.

Falk W Lohoff - One of the best experts on this subject based on the ideXlab platform.

  • association between polymorphisms in the vesicular monoamine transporter 1 gene vmat1 slc18a1 on Chromosome 8p and schizophrenia
    Neuropsychobiology, 2008
    Co-Authors: Falk W Lohoff, Andrew E Weller, Paul J Bloch, Russell J Buono, Glenn A Doyle, Thomas N Ferraro, Wade H Berrettini
    Abstract:

    Linkage studies have suggested a susceptibility locus for schizophrenia (SZ) exists on Chromosome 8p21–22. The vesicular monoamine transporter 1 gene (VMAT1), also known as SLC18A1, maps to this SZ su

  • association between variation in the vesicular monoamine transporter 1 gene on Chromosome 8p and anxiety related personality traits
    Neuroscience Letters, 2008
    Co-Authors: Falk W Lohoff, Thomas N Ferraro, Marion Lautenschlager, Johannes Mohr, Thomas Sander, Jurgen Gallinat
    Abstract:

    Vesicular monoamine transporters are involved in the presynaptic packaging of norepinephrine, dopamine and serotonin into storage vesicles. The vesicles release their content upon arrival of an action potential into the synaptic cleft. Dysregulation of monoaminergic neurotransmission has been long postulated to play a relevant role in the etiology of neuropsychiatric disorders. The gene encoding the vesicular monoamine transporter 1 (VMAT1/SLC18A1) maps to Chromosome 8p21, a region where several linkage peaks overlap between schizophrenia, bipolar disorder and anxiety-related personality traits. In this study, we tested the hypothesis that the missence variation Thr136Ile in the VMAT1/SLC18A1 gene is associated with anxiety-related personality traits. We tested a total of 337 unrelated subjects of German descent (167 male, 170 female). All participants were carefully screened for psychiatric disorders. The self-report State-Trait Anxiety Inventory (STAI) was completed by all subjects. Genotypes were obtained for the Thr136Ile (rs1390938) variation in the VMAT1 gene for all subjects. Genotype effects on personality variables were computed with MANOVA including age as a co-variant and gender as independent factor (MANCOVA). Results show that STAI scores were significantly affected by genotype (F=3.108; d.f.=4,331; p=0.015) and age (F=7.233; d.f.=2,331; p=0.001) but not by gender. A gender-by-genotype effect was observed for both the STAI state (p=0.052) and trait score (p=0.035). Dissection of the group by gender and subsequent contrast analysis of the genotype effects performed within the female group showed significant results (STAI state: Thr/Ile vs. Ile/Ile: T=4.408, p=0.0004; STAI trait: Thr/Ile vs. Ile/Ile: T=3.074, p=0.009) but not in the male group. Our findings support the hypothesis that anxiety-related personality traits are associated with variation in the VMAT1/SLC18A1 gene.

Kenneth S Koeneman - One of the best experts on this subject based on the ideXlab platform.

  • decreased nkx3 1 protein expression in focal prostatic atrophy prostatic intraepithelial neoplasia and adenocarcinoma association with gleason score and Chromosome 8p deletion bethel cr faith d li x guan b hicks jl lan f jenkins rb bieberich cj de ma
    Urologic Oncology-seminars and Original Investigations, 2008
    Co-Authors: Kenneth S Koeneman
    Abstract:

    NKX3.1 is a homeobox gene located at Chromosome 8p21.2, and one copy is frequently deleted in prostate carcinoma. Prior studies of NKX3.1 mRNA and protein in human prostate cancer and prostatic intraepithelial neoplasia (PIN) have been conflicting, and expression in focal prostate atrophy lesions has not been investigated. Immunohistochemical staining for NKX3.1 on human tissue microarrays was decreased in most focal atrophy and PIN lesions. In carcinoma, staining was inversely correlated with Gleason grade. Fluorescence in situ hybridization showed that no cases of atrophy had loss or gain of 8p, 8 centromere, or 8q24 (C-MYC), and only 12% of high-grade PIN lesions harbored loss of 8p. By contrast, NKX3.1 staining in carcinoma was correlated with 8p loss and allelic loss was inversely related to Gleason pattern. Quantitative reverse transcription-PCR for NKX3.1 mRNA using microdissected atrophy revealed a concordance with protein in 5 of 7 cases. In carcinoma, mRNA levels were decreased in 6 of 12 cases but mRNA levels correlated with protein levels in only 4 of 12 cases, indicating translational or post-translational control. In summary, NKX3.1 protein is reduced in focal atrophy and PIN but is not related to 8p allelic loss in these lesions. Therefore, whereas genetic disruption of NKX3.1 in mice leads to PIN, nongenetic mechanisms reduce NKX3.1 protein levels early in human prostate carcinogenesis, which may facilitate both proliferation and DNA damage in atrophic and PIN cells. Monoallelic deletions on Chromosome 8p are associated with more advanced invasive and aggressive disease.

Lunxiu Qin - One of the best experts on this subject based on the ideXlab platform.

  • the predictive value of Chromosome 8p deletion for metastasis of hepatocellular carcinoma a summary of works in 10 years
    Frontiers of Medicine in China, 2008
    Co-Authors: Lunxiu Qin, Huliang Jia, Zhaoyou Tang, Xin Yuan Guan, Ning Ren
    Abstract:

    Hepatocellular carcinoma (HCC) represents an extremely poor prognostic cancer, which is mainly due to the high frequency of metastasis/recurrence after surgical operation. Exploring the molecular mechanisms involved in HCC metastasis could be helpful in the prediction and early diagnosis of HCC recurrence and could also provide new therapeutic targets for HCC metastasis. In the recent decade, we analyzed the genomic aberrations of the clinical specimens, as well as the metastatic models and cell lines of human HCC to identify the genetic markers related to HCC metastasis and to verify their clinical values in the prediction and control of metastasis of HCC. Using the comparative genomic hybridization (CGH) technique, we compared the differences of chromosomal aberrations between primary HCC tumors and their matched metastatic lesions, and found that Chromosome 8p deletions might contribute to HCC metastasis. This novel finding was further confirmed by comparison between nude mice models of HCC with different metastatic potentials. By the more sensitive genome-wide microsatellite analysis, 8p deletion was defined to 8p23.3 and 8p11.2, which are two likely regions harboring metastasis-related genes of HCC. Using ‘8p-specific’ microarrays, two novel metastatic suppressors (HTPAP and MRSA) were identified, and were proven to suppress in vitro invasion and in vivo metastasis of HCC. Clinical studies indicate that 8p deletion detected in HCC or circulating plasma DNA of patients is a useful predictor for metastatic recurrence and prognosis, even for patients with early stage HCC. These novel findings are regarded as important advances in the study of the molecular mechanisms of HCC metastasis, which provide not only a holistic view on the molecular cytogenetic bases of HCC metastasis, but also candidate regions for further study to identify metastatic suppressor genes.

  • identification of msra gene on Chromosome 8p as a candidate metastasis suppressor for human hepatitis b virus positive hepatocellular carcinoma
    BMC Cancer, 2007
    Co-Authors: Kefeng Lei, Yanfang Wang, Xiaoqun Zhu, Bingsheng Sun, Huliang Jia, Ning Ren, Huichuan Sun, Lu Wang, Zhaoyou Tang, Lunxiu Qin
    Abstract:

    Background The prognosis of patients with hepatocellular carcinoma (HCC) still remains very dismal, which is mainly due to metastasis. In our previous studies, we found that Chromosome 8p deletions might contribute to metastasis of HCC. In this study, we aimed to identify the candidate metastatic suppressor gene on Chromosome 8p.

  • htpap gene on Chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma
    Oncogene, 2006
    Co-Authors: Huliang Jia, Ning Ren, Huichuan Sun, Zhaoyou Tang, Yilin Wang, Longrong Wang, Yinkun Liu, Lunxiu Qin
    Abstract:

    Our previous studies suggested that Chromosome 8p deletion is associated with metastasis of hepatocellular carcinoma (HCC), in which some novel metastasis suppressor genes might be harbored. The present study aimed to identify the metastatic suppressor gene(s). A cDNA chip was constructed with the expressed sequence tags (ESTs) from Chromosome 8p and used to compare the difference of expression profiling between the MHCC97-H and MHCC97-L cell lines with different metastatic potentials and similar genetic backgrounds. In all, 10 ESTs were significantly downregulated in MHCC97-H cell line with higher metastatic potential. One full-length gene, HTPAP (phosphatidic acid phosphatase type 2 domain containing 1B), was identified at Chromosome 8p12. Sequencing and bioinformatic analyses revealed that HTPAP has 826 bp and encodes a putative protein of 175 amino acids with a transmembrane segment at the NH2 terminus, two protein kinase C phosphorylation site and one tyrosine kinase phosphorylation site. Its expression level in metastatic tumor tissues was much lower than that of primary HCC tissues. Both in vitro and in vivo assays suggested that HTPAP could suppress the invasion and metastasis of HCC. These suggested that HTPAP is a novel metastatic suppressor gene for HCC. The mechanism of the effect of HTPAP on HCC metastasis is not clear yet and deserves further investigation.

  • the prognostic value of circulating plasma dna level and its allelic imbalance on Chromosome 8p in patients with hepatocellular carcinoma
    Journal of Cancer Research and Clinical Oncology, 2006
    Co-Authors: Ning Ren, Lunxiu Qin, Yinkun Liu, Boheng Zhang, Zhaoyou Tang
    Abstract:

    Purpose: We demonstrated that Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma (HCC). This study assesses the value of circulating plasma DNA level and its allelic imbalance (AI) on Chromosome 8p in the prediction of HCC prognosis. Methods: Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. The HCC and adjacent non-tumor liver tissues were obtained from surgical specimens. Plasma DNA was extracted and quantified. Two microsatellite markers on Chromosome 8p, D8S258 and D8S264, were selected and used in the AI analysis. Results: The circulating plasma DNA level was found to closely associate with tumor size (P=0.008) and TNM stage (P=0.040), negatively associate with the 3-year disease-free survival (DFS) (P=0.017) and overall survival (OS) (P=0.001). AI at D8S258 in plasma DNA was significantly correlated with tumor differentiation (P=0.050), TNM stage (P=0.010), and vascular invasion (P=0.023), negatively correlated with the 3-year DFS (P=0.005) and OS (P=0.036). However, AI at D8S264 was only closely associated with 3-year DFS (P=0.014). Combined detection of AI at D8S258 and circulating plasma DNA level was independently associated with DFS (P=0.018) and OS (P=0.002) of patients with HCC. For patients with both AI at D8S258 and a higher level of plasma DNA, the 3-year DFS and 3-year OS rates were decreased remarkably (P=0.014 and 0.044). Conclusion: Combination of circulating plasma DNA level and AI at D8S258 might be an independent predictor for prognosis of HCC patients.

  • Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared
    Journal of Cancer Research and Clinical Oncology, 2001
    Co-Authors: Lunxiu Qin, Yinkun Liu, Xin Yuan Guan, Zhonghao Tang, Xu Dong Zhou, Z Y Lin, F X Sun, Jie Tian, Svetlana Pack, Zhengping Zhuang
    Abstract:

    Recently, we found that Chromosome 8p deletion might be associated with hepatocellular carcinoma (HCC) metastasis by analyzing the differences in chromosomal alterations between primary tumors and their matched metastatic lesions of HCC with comparative genomic hybridization (CGH) (Qin et al. 1999). To further confirm this interesting finding, the genomic changes of two models bearing human HCC with different metastatic potentials (LCI-D20 and LCI-D35), and the new human HCC cell line with high metastatic potential (MHCC97) were analyzed by CGH. Gains on 1q, 6q, 7p, and 8q, and losses on 13p, 14p, 19p, 21, and 22 were detected in both LCI-D20 and LCI-D35 models. However, high copy number amplification of a minimum region at 1q12-q22 and 12q, and deletions on 1p32-pter, 3p21-pter, 8p, 9p, 10q, 14q, and 15p were detected only in the LCI-D20 model. Gains on 1p21-p32, 2p13-p21, 6p12-pter, 9p, 15q, and 16q11-q21, and losses on 2p23-pter, 4q24-qter, 7q31-qter, 12q, 17p, and 18 were detected only in the LCI-D35 model. The chromosomal aberration patterns in the MHCC97 cell line were similar to its parent LCI-D20 model, except that gains on 19q and losses on 4, 5, 10q, and 13q were found only in the cell line. These results provide some indirect clues to the metastasis-related chromosomal aberrations of HCC and further support the finding that 8p deletion is associated with HCC metastasis. 1q12–22 and 12q might harbor a novel oncogene(s) that contributes to the development and progression of HCC. Amplification on 8q and deletions on 4q and 17p may be not necessary for HCC metastasis.