Xiu-Ping Liu

Fudan University, Shanghai, Shanghai Shi, China

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Publications (19)60.82 Total impact

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    ABSTRACT: Hypoxia, a common phenomenon during the development of malignant solid tumors including breast cancer, serves to propagate a cascade of molecular pathways triggered by hypoxia-inducible factor-1α (HIF-1α). Carbonic anhydrase IX (CA IX), one of the target genes of HIF-1α, has been reported to be involved in progression of malignant tumors. The objective of this study was to investigate the expression of HIF-1α and CA IX in hypoxia, involvement of CA IX in the regulation of migration and invasion/metastasis and its prognostic significance in breast cancer. We used cobalt chloride (CoCl2) as a hypoxia-mimetic agent and found that the expression of HIF-1α protein, CA IX mRNA and protein, is effectively upregulated, except for HIF-1α mRNA. Data showed that the elevated CA IX expression is closely related to in vitro cell migration and invasion, and the underlying mechanism of this process may be associated with epithelial-mesenchymal transition (EMT). The study of clinical tissue samples also demonstrated that CA IX is an independent prognostic marker that may serve as a useful clinical biomarker for predicting tumor progression and the invasion/metastasis of breast cancer. These results provide further insight into the role of CA IX in tumor progression and put forward further strong evidence as well as new consideration for CA IX target therapy.
    No preview · Article · Nov 2015 · International Journal of Oncology
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    ABSTRACT: Aims: Cytoplasmic polyadenylation element binding proteins (CPEBs) are RNA-binding proteins that regulate translation by inducing cytoplasmic polyadenylation. CPEB4 has been reported in association with tumor growth, vascularization, and invasion in several cancers. To date, the expression of CPEB4 with clinical prognosis of breast cancer was never reported before. We aim to investigate the expression of CPEB4 and its prognostic significance in invasive ductal breast carcinoma. Methods: Immunohistochemical staining of CPEB4 and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor was performed in 107 invasive ductal carcinoma (IDC) samples, and prognostic significance was evaluated. Results: High expression of CPEB4 was observed in 48.6% of IDC samples. Elevated CPEB4 expression was possibly related to increased histological grading (P=0.037) and N stage (P<0.001). Patients with high expression of CPEB4 showed shorter overall survival (P=0.001). High CPEB4 expression was an independent prognostic factor for overall survival (P=0.022, hazard ratio =4.344, 95% confidence interval =1.235-15.283). Conclusion: High CPEB4 expression is associated with increased histological grading and N stage, and it can serve as an independent prognostic factor in IDC.
    No preview · Article · Nov 2015 · OncoTargets and Therapy
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    ABSTRACT: Breast cancers bear overexpression of neurokinin-1 (NK-1). The aim of this study was to investigate the relationship between NK-1 and EGFR in triple negative breast cancers (TNBCs). Immunohistochemistry was performed to investigate NK-1 and EGFR expressions in TNBCs. [Sar(9),Met(O2)(11)] substance P (SMSP) was used to activate NK-1 in two TNBC cell lines, MDA-MB-231 and MDA-MB-468. L-733060 and siRNA against NK-1 was used to inhibit NK-1. The in vitro regulatory effect of NK-1 was determined using CCK-8 proliferation assay. The effects of NK-1 activation and inhibition on EGFR and its downstreaming pathway were analyzed using western blot and real-time quantitative PCR. We found that the proportion of EGFR positive cases was increased with the increasement of NK-1 levels. SMSP could promote the proliferation of TNBC cells, while L-733060 and siRNA could inhibit cell proliferation and induce apoptosis. Moreover, SMSP could enhance expressions of phosphorylation (p)-EGFR and EGFR, and activate p-Akt and p-Erk. NK1-siRNA could decrease p-EGFR, p-Akt and p-Erk. In the presence of cetuximab (0.2 mg/mL), SMSP still could stimulate cell proliferation, and activate p-EGFR. However, in the presence of erlotinib (10 μM), SMSP could not stimulate cell proliferation and could not activate p-EGFR. Our study showed the interaction between NK-1 and EGFR in TNBCs. These results suggested NK-1 may regulate TNBC proliferation through EGFR phosphorylation, and the curative effect of EGFR monoclonal antibodies may be affected by NK-1 activation. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Mar 2015 · Cellular Signalling
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    Jingbo Wu · Xiao-Jing Li · Wei Zhu · Xiu-Ping Liu
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    ABSTRACT: The aim of the present study was to investigate human papillomavirus (HPV) infection and p16(INK4A) and p53 protein expression, to evaluate their roles in the pathological diagnosis and grading for cervical intraepithelial neoplasia (CIN). The detection of HPV DNA and p16(INK4A) and p53 protein expression were examined in a panel of clinical tissue samples using polymerase chain reaction or immunohistochemistry. In 104 cases, HPV16/18 DNA was identified in 49.0% and HPV6/11 DNA in 9.6% of cases. While in 203 cases, 74.4% positively expressed p16(INK4A) and 47.3% positively expressed p53. The expression of p16(INK4A) exhibited a significantly higher rate in the CIN I group than in the squamous metaplasia coupled with hyperplasia group (SMH; P<0.0001) and the CIN II-III group (P=0.005). A marked correlation was revealed between the band-like staining pattern of p16(INK4A) and HPV16/18 infection. On the contrary, p53 expression was not found to significantly correlate with CIN grade or the HPV16/18 infection status. These results suggested that p16(INK4A) expression correlates with a higher grade of CIN and may be used as a diagnostic marker to distinguish between CIN I and SMH, as well as between CIN I and CIN II-III.
    Preview · Article · Mar 2014 · Oncology letters
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    ABSTRACT: The oligodendroglioma (OG) type of glial cell tumors accounts for 2-5% of primary brain neoplasms and 4-15% of gliomas diagnosed worldwide. Allelic losses on 1p, or on 1p and 19q, correlate with chemotherapy response and good prognosis in OG patients; however, the underlying mechanisms are not yet clearly defined. Therefore, we utilized a quantitative proteomics strategy that combined 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) to identify molecular signatures, reveal mechanisms, and develop predictive markers of OG patients with 1p loss of heterozygosity (LOH). An initial screening of four OG patients with 1p LOH and four without were identified, and 449 differentially expressed proteins were quantified, 13 of which were significantly different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway suggested that 1p LOH may affect the actin network in OG. The differential expression of four of the 13 candidates (UBA1, ubiquitin-like modifier activating enzyme 1; ATP6V1E1, ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E1; MAP2, microtubule-associated protein 2; and HMGB1, high-mobility group protein B1) was validated in 39 additional OG samples using immunohistochemistry. Decision tree modeling indicated that MAP2 expression is a powerful predictor of 1p LOH. Our results not only demonstrate the utility of iTRAQ-based high-throughput quantitative proteomic analysis in glioma research, but also provide novel markers that may help to reveal the mechanisms of 1p LOH-associated chemosensitivity, and to design diagnostic and prognostic assays and therapeutics for OG.
    No preview · Article · Oct 2012 · Journal of proteomics
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    ABSTRACT: CCAAT enhancer binding protein-α (C/EBP-α) is a transcript factor that regulates adipocyte differentiation and induces apoptosis in hepatic stellate cells (HSCs) in vivo and in vitro. However, the effect of C/EBP-α on hepatocytes in vivo remains unknown. This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl(4)-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl(4)-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced significantly. Immunohistochemistry and TUNEL assay results showed an increase of apoptosis in HSCs, but hepatocytes were less affected. C/EBP-α induced differential apoptotic effects in hepatocytes and HSCs in vitro and in vivo. This differential effect could be a potential target for the treatment of hepatic fibrosis with little hepatic toxicity.
    No preview · Article · Feb 2012 · Apoptosis
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    ABSTRACT: Multidrug resistance is the most predominant phenomenon leading to chemotherapy treatment failure in breast cancer patients. Despite many studies having suggested that overexpression of epidermal growth factor receptor (EGFR) is a potent predictor of malignancy in cancers, systematic research of EGFR in multidrug resistant (MDR) breast cancer cells is lacking. In order to clarify the role of EGFR in MDR breast cancer cells, MCF7/Adr expressing relatively higher EGFR, and its parental cell line MCF7 expressing relatively lower EGFR, were chosen for this study. Knockdown of EGFR by siRNA in MCF7/Adr cells showed that EGFR siRNA inhibits cell migration, invasion and proliferation in vitro; converse effects were observed in MCF7 cells transfected with pcDNA3.0-EGFR plasmid. Moreover, we found that EGFR upregulated migration and invasion via EMMPRIN, MMP2 and MMP9 in addition to promoting cell cycle passage via elevation of cyclin D1 and CDK4 in MDR breast cancer cells. Interestingly, MCF7/Adr cells not expressing EGFR showed significant decrease of P-glycoprotein (P-gp) and ABCG2 expression levels, and became more sensitive to treatment of adriamycin (ADR) and paclitaxel (Taxol); the above results indicated that MDR of cancer cells is related to S-phase arrest. In conclusion, EGFR is an important factor enhancing the malignancy of MDR breast cancer cells, partially, inducing MDR. Anti-EGFR therapy may improve outcome in chemorefractory breast cancer patients.
    Preview · Article · Jul 2011 · International Journal of Oncology
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    ABSTRACT: We aimed to gain a mechanistic understanding of the role of RACK1 in breast carcinoma migration/metastasis. Migration assays were conducted in breast carcinoma cell lines. siRNA targeting RACK1 as well as the Rho kinase inhibitor were also applied. Immunoprecipitation and immunofluorescence were used to study the RACK1/RhoA interaction. GTP-Rho pull-down assays were performed to assess the activation of RhoA. We also conducted immunohistochemistry in 160 breast carcinoma samples. Experiments in vitro showed that RACK1 promotes migration via interaction with RhoA and activation of the RhoA/Rho kinase pathway. Immunohistochemistry in 160 samples revealed that RACK1 is strongly correlated with accepted tumor spread indicators and RhoA (all P < 0.05). Kaplan-Meier survival analysis indicated a correlation between higher RACK1 expression and shorter survival times (P < 0.001). RACK1 is a prognostic factor that promotes breast carcinoma migration/metastasis by interacting with RhoA and activating the RhoA/Rho kinase pathway.
    No preview · Article · May 2010 · Breast Cancer Research and Treatment
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    ABSTRACT: A yeast two-hybrid system was utilized to identify novel PI3K p110alpha-interacting proteins, of which receptor of activated protein kinase C1 (RACK1) was chosen for successive detailed analyses. Our aim was to investigate the function(s) of RACK1 and its involvement in mechanisms of breast carcinoma proliferation and invasion/metastasis. Experiments in breast carcinoma cell lines stably transfected with RACK1, as well as nude mouse models, showed that RACK1 promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo. Conversely, knockdown of RACK1 by siRNA in vitro inhibited proliferation, migration, and invasion. In cell lines stably transfected with RACK1, p-AKT, cyclin D1, cyclin D3, and CD147 expression, as well as MMP2 activity, were elevated. RACK1-induced migration could be inhibited by the addition of Rho-kinase inhibitor. In 160 breast carcinoma cases, survival analyses established that RACK1 is an independent prognostic factor for poor outcome (P < 0.001). In conclusion, RACK1 is an independent prognosis-related factor and promotes breast carcinoma proliferation and invasion/metastasis in vitro and in vivo.
    No preview · Article · Nov 2009 · Breast Cancer Research and Treatment
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    ABSTRACT: We aimed to investigate the expression of RACK1 in breast cancer, evaluate its role in predicting prognosis and compare with commonly used biomarkers: Ki67, ER, PR and HER-2 for patients with breast cancer. The RACK1 expression and its clinical significance were examined in 160 breast carcinoma patients using immunohistochemistry. Correlations of RACK1 expression with other commonly used biomarkers and survival analyses were assessed. Immunohistochemistry results showed that the number of RACK1 cases scoring 0, 1, and 2 were 66, 54, and 40, respectively. RACK1 staining was strongly related to clinical stage, histological grade, Ki67, ER, PR and HER-2 (all p < 0.05). Consistently, all of the cases exhibiting RACK1 staining score 0 were survivors, whereas the majority (55.0%) of those exhibiting RACK1 staining score 2 were deaths. Kaplan-Meier survival analysis of 160 cases revealed a correlation between higher RACK1 expression levels and shorter overall survival times (p < 0.001). Univariate and multivariate analyses revealed that RACK1, tumor size, lymph node metastasis, and HER-2 were independent prognostic factors (all p < 0.05). Interestingly, receiver operator characteristic (ROC) curves showed that the ROC areas for RACK1, Ki67, ER, PR and HER-2 were 0.833, 0.766, 0.446, 0.387, and 0.689, respectively, and the superiority of RACK1 in sensitivity and specificity as biomarker was demonstrated. To our knowledge, it is the first time to investigate the expression of RACK1, and identified that RACK1 is a superior independent biomarker for diagnosis and prognosis comparing with currently widely used diagnostic index in breast carcinoma.
    Preview · Article · Sep 2009 · International Journal of Cancer
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    ABSTRACT: Special AT-rich sequence binding protein (SATB) 1 has been proposed to act as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. Here we found that SATB1 expression is upregulated in multidrug-resistant breast cancer cells that exhibit higher invasive potential than the parental cells. Apart from accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was demonstrated to confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1-overexpressing transfectants. SATB1 depletion could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in vitro and in vivo. The SATB1-induced P-glycoprotein-mediated MDR could be reversed by treatment with anti-P-glycoprotein mAb. Moreover, SATB1 plays an important role in anti-apoptotic activity in MCF7/ADR cells in response to adriamycin treatment, which suggests another mechanism contributing to SATB1-related MDR of breast cancers. These data provide new insights into the mode by which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in this process.
    Preview · Article · Sep 2009 · Cancer Science
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    ABSTRACT: Besides its therapeutic effects, chemotherapeutic agents also enhance the malignancy of treated cancers in clinical situations. Recently, epithelial-mesenchymal transition (EMT) has attracted attention in studies of tumor progression. We aimed to test whether transient Adriamycin treatment induces EMT and apoptosis simultaneously in cancer cells, clarify why the same type of cells responds differentially (i.e., apoptosis, EMT) to Adriamycin treatment, and elucidate the role of Twist1, the master regulator of EMT, in this process. In unsynchronized MCF7 cells or cells synchronized at different phases, apoptosis, EMT, and concurrent events [multidrug resistance (MDR) and tumor invasion] after Adriamycin or/and Twist1 small interfering RNA treatment were examined in vitro and in vivo. The Adriamycin-induced Twist1 expression and the interaction of Twist1 with p53-Mdm2 were examined by immunoblotting and immunoprecipitation, respectively. We showed in vitro that Adriamycin induced EMT and apoptosis simultaneously in a cell cycle-dependent manner. Only the cells undergoing EMT displayed enhanced invasion and MDR. Twist1 depletion completely blocked the mesenchymal transformation, partially reversed MDR, and greatly abolished invasion induced by Adriamycin. Also, we confirmed in vivo that Twist1 RNA interference improved the efficacy of Adriamycin for breast cancers. Further, Twist1 reduction in Adriamycin-treated cells promoted p53-dependent p21 induction and disrupted the association of p53 with Mdm2. Our studies show the diverse responses to Adriamycin treatment in cells at different phases, suggest an unrecognized role of EMT in regulating MDR and invasion, and show the efficacy of Twist1 RNA interference in Adriamycin-based chemotherapies for breast cancer.
    Preview · Article · Apr 2009 · Clinical Cancer Research
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    ABSTRACT: Lymph-node metastasis is a main factor causing poor prognosis of patients with gastric cancer (GC). In order to determine the genes involved in lymph-node metastasis, we compared primary tumors with their synchronous lymph-node metastases for DNA sequence copy number aberrations (DSCNAs) in 20 patients diagnosed as having intestinal-type GC using comparative genomic hybridization (CGH). The results showed that some DSCNAs (gains at 8q, 13q, 5p, 7 and X, and losses at 1p, 17p, 19, 21q and 22q) were frequently found in both primary tumors and their metastases. However, metastases often contained DSCNAs that were not found in corresponding primary tumors, and gain at 20q12-13 and losses at 21qcen-21, 4q and 14q22-ter were significantly more frequently observed in metastatic lesions than in their primary tumors (10:2, 9:0, 6:0, and 7:0 between metastases and corresponding primary tumors, respectively). Our data indicate that gain at 20q12-13 and losses at 21qcen-21, 4q, and 14q22-ter are involved in lymph-node metastases, and that these chromosomal regions may contain the genes related to lymph-node metastases in intestinal-type GC.
    No preview · Article · Dec 2008 · Pathology - Research and Practice
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    ABSTRACT: Ubiquitin carboxy terminal hydrolase-L1 (UCH-L1) belongs to the UCH proteases family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. Previous research showed that UCH-L1 was expressed in mouse retinal cells and testicular germ cells, and its function was associated with apoptosis. But it is still unclear whether UCH-L1 is concerned with apoptosis in tumor cells. In order to clarify the role of UCH-L1 in tumor cells, multi-drug resistance (MDR) human breast carcinoma cell line MCF7/Adr, that expresses relatively high UCH-L1, and its parental cell line MCF7, that expresses relatively low UCH-L1, were chosen for this study. We transfected pcDNA3.1-UCH-L1 plasmid and UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively. Using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, western blot, Hoechst 33258 staining assay and flow cytometry, we found that over-expression of UCH-L1 in MCF7 cells induced apoptosis. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Moreover, to explore the mechanism underling these observations, we further investigated the expression of phospho-Akt and its downstream signal phospho-IkB-alpha and other signal molecules including Fas, Fas-L, Trail, DR4, DR5, Bax, cytochrome C, active caspase-3, phospho-p53, phospho-Mdm-2, Bcl-2, Bcl-xL, p21 and p27. The results indicated that the process of apoptosis triggered by UCH-L1 is, at least in part, probably through Phosphoinositide 3-kinase (PI3K)/Akt signal pathway. Our findings suggest that modulating the ubiquitination and deubiquitination pathway could be a novel method for tumor therapy.
    Preview · Article · Dec 2008 · International Journal of Oncology
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    ABSTRACT: Multidrug-resistant cancer cells overexpressing P-glycoprotein (P-gp) display variations in invasive and metastatic ability through the upregulation of the extracellular matrix metalloproteinase (MMP) inducer (CD147). However, the direct linkage between these two proteins is still unclear. We used immunoprecipitation, immunofluorescence analysis, migration and invasion assays, drug sensitivity assay and Western blot to measure the physical and functional interaction between P-gp and CD147. Then we transfected vectors carrying ubiquitin C-terminal hydrolase L1 (UCH-L1) or UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively, and investigated the role of UCH-L1 in the regulation of the expression and degradation of P-gp, CD147 and MMP-1, MMP-2, and MMP-9 by quantitative real-time polymerase chain reaction, Western blot and immunoprecipitation. In this paper, we showed that P-gp and CD147 interacted with each other, and that the ubiquitin-proteasome pathway played an important role in the turnover of them. In addition, we found that inhibition of N-glycosylation increased the ubiquitination and degradation of P-gp and CD147, and affected their function. UCH-L1 not only regulated the expression of P-gp, CD147 and MMP-1, MMP-2, and MMP-9, but also the ubiquitination and degradation of P-gp and CD147 in breast cancer cells. Our results demonstrate a mechanism underlying the linkage between multidrug resistance and tumor metastasis, and suggest for the first time that modulating the ubiquitination of P-gp and CD147 might be a novel method for tumor therapy.
    No preview · Article · Feb 2008 · Chemotherapy
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    ABSTRACT: To analyze the correlation of DNA sequence copy number aberrations (DSCNAs)with clinicopathologic parameters in patients with colorectal cancer(CRC). Comparative genomic hybridization (CGH) method was used in analysis of 73 cases with CRC. Statistical analysis was performed using Stat View statistical software package(5.0). Loss of 8pl2-pter and gain of 8q23-qter were linked to nodal metastasis, while loss of 18q12-qter and gain of 8q23-qter were associated with distant organ metastasis at diagnosis and (or) recurrence after surgery. Moreover, losses of 8pl2-pter and 18q12-qter and gain of 8q23-qter were associated significantly with unfavorable prognosis. Multivariate analysis revealed that loss of 18q12-qter was an independent prognostic marker. Our findings indicate that genetic aberrations detected by CGH may predict outcome in patients with CRC, and may provide useful information for clinical treatment. Comparative genomic hybridization;
    No preview · Article · Jun 2007 · Zhonghua zhong liu za zhi [Chinese journal of oncology]
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    ABSTRACT: To obtain comprehensive information regarding the correlation between genomic changes and clinicopathological parameters such as disease stage, metastases, and survival, we investigated genomic changes by comparative genomic hybridization (CGH) in 73 patients with colorectal cancer (CRC), and assessed the associations of such charges with clinicopathological parameters. Gains of 8q21-22, 13q21-31 and 20q12-qter and loss of 17p12-pter were detected in >50% of stage I tumors. Gain of 8q23-qter and losses of 8p12-pter and 18q12-qter were observed more frequently in stage III/IV tumors than in stage I tumors (all P<0.05). Loss of 8p12-pter and gain of 8q23-qter were linked to nodal metastasis (all P<0.05). Loss of 18q12-qter and gain of 8q23-qter were associated with distant organ metastasis at diagnosis and/or recurrence after surgery (all P<0.05). Moreover, losses of 8p12-pter and 18q12-qter and gains of 8q23 and 8q24-qter were associated significantly with unfavorable prognosis (all P<0.05). Furthermore, combined examination of the above four changes can provide a more accurate assessment for patient's prognosis. Specifically, 11 of 19 patients with these four changes died, but only 1 of 21 cases without these four changes died during the follow-up period (P<0.0001). Multivariate analysis revealed that loss of 18q12-qter is an independent prognostic marker (P=0.031). Our findings indicate that genetic aberrations detected by CGH may predict outcome in patients with CRC.
    No preview · Article · Feb 2007 · Oncology Reports
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    ABSTRACT: To data, there have been no comprehensive cytogenetic studies of mucinous colorectal carcinomas (MUCs). We used comparative genomic hybridization (CGH) and laser scanning cytometry (LSC), to analyze cytogenetic changes in 21 MUCs and to compare the results with those of our previous study of 60 non-MUCs. Six of 21 MUCs were aneuploid and 15 were diploid. Gains of 13q, 8q, 2q, 12p and 18p were more frequent aberrations. Recurrent decreases in DNA copy number were found frequently at 17p, 22q, 1p, 16p and 8p. Amplifications of 8q, 5p, 12, 18p, 13q and 20p were observed in aneuploid tumors. The average number of DNA sequence copy number aberrations (DSCNAs) was significantly higher in aneuploid MUCs than in diploid ones. Aneuploid MUCs were clinicopathologically more aggressive, with greater lymph node involvement, distant organ metastasis, recurrence after surgery, higher stage and poorer prognoses. Gain or amplification of 18p was detected in 5 of 6 aneuploid MUCs but not in diploid MUCs or non-MUCs. When the average number of DSCNAs was compared among MUCs and well, moderately, and poorly differentiated adenocarcinomas, the average number of DSCNAs was significantly lower in diploid MUCs; however, with aneuploid tumors, the average number of DSCNAs in MUCs was similar to that in poorly differentiated adenocarcinomas but higher than that in well and moderately differentiated cancers. Moreover, tumor cells were well differentiated in diploid MUCs but poorly differentiated in aneuploid MUCs. These data suggest that MUCs have two types with different genetic pathways, histologic characteristics, and behavior.
    No preview · Article · Oct 2004 · International Journal of Oncology
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    ABSTRACT: Matrilysin is known to play an important role in tumor invasion, but it is not known yet whether there is a direct relationship between matrilysin expression and cell proliferation. Therefore, we compared expression of matrilysin with expression of Ki-67, a marker of cell proliferation, at different tumor areas in 130 advanced gastric carcinomas. Both matrilysin and Ki-67 were distributed heterogeneously in tumor tissue. Matrilysin frequently was expressed at the invasive front, whereas Ki-67-positive cells frequently were located both at the tumor surface and in central tumor cell nests. The patterns of gastric cancer cell invasion into the surrounding tissues are described as alpha-infiltration, beta-infiltration, and gamma-infiltration, respectively, according to the guidelines of the Japanese Research Society for Gastric Cancer Study. The mean matrilysin labeling index (LI) of gamma-infiltration tumors at the invasive front was significantly greater than that of alpha- and beta-infiltration tumors (P =.01). In contrast to the matrilysin LI, the mean Ki-67 LI of gamma-infiltration tumors was significantly lower than that of alpha- and beta-infiltration tumors (P =.02). Moreover, Ki-67 antigen was absent in matrilysin-positive tumor cells and vice versa. We concluded that matrilysin expression was related inversely with proliferative activity of tumor cells and that matrilysin expression could possibly serve as a useful marker of tumor invasion.
    No preview · Article · Aug 2002 · Human Pathlogy