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Li-Li Tao,
Yuan-Yuan Cheng,
Di Ding,
Shuang Mei,
Jia-Wen Xu,
Juan Yu,
Qi Ou-Yang,
Long Deng,
Qi Chen,
Qing-Quan Li,
Zu-De Xu, Xiu-Ping Liu
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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.
Apoptosis 02/2012; 17(5):492-502. · 4.07 Impact Factor
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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.
International Journal of Oncology 07/2011; 39(6):1501-9. · 2.40 Impact Factor
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ABSTRACT: The reason for and consequences of BCL2L10 down-regulation in gastric carcinoma are poorly understood. Our aim was to investigate the function of the protein BCL2L10 in gastric carcinoma. We investigated BCL2L10 expression using quantitative real-time PCR and immunoblotting. The methylation status of the BCL2L10 gene promoter was examined by bisulphite sequencing in fresh gastric normal and carcinoma tissues. We studied apoptosis and proliferation regulation in gastric cancer cell lines using flow cytometry, fluorescence staining, murine xenografting and immunoblotting. Pathway inhibitors were applied to confirm the major pathways involved in apoptosis or proliferation regulation. We observed significant correlations between lower BCL2L10 expression and CpG island hypermethylation of the BCL2L10 gene promoter in gastric carcinoma, apoptosis induced by over-expressed BCL2L10 through mitochondrial pathways, and proliferation accelerated by BCL2L10 siRNA via the PI3K-Akt signalling pathway in gastric cancer cell lines. The pro-apoptotic effect of BCL2L10 and growth promotion by BCL2L10 siRNA in gastric cancer cells suggest that it may be a tumour suppressor.
The Journal of Pathology 02/2011; 223(3):400-9. · 6.32 Impact Factor
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ABSTRACT: BCL2L10 protein is an apoptosis-related member of the Bcl-2 protein family. The clinical significance of its expression in gastric carcinoma is poorly understood. The aim was to investigate BCL2L10 expression and its clinical and prognostic significance in gastric carcinoma patients.
Immunohistochemistry, real-time polymerase chain reaction (PCR) and immunoblotting all revealed extensive loss of BCL2L10 expression in gastric cancer cells. The scaled BCL2L10 expression data was categorized into three groups (groups 0-2) to facilitate statistical analysis. A significant correlation was observed between the lower BCL2L10 expression group and shorter disease-free survival (P=1.956×10(-18)). Multivariate regression analysis showed that loss of BCL2L10 protein expression [P=4.883×10(-8), hazard ratio (HR)=0.252] is an independent prognostic predictor of gastric carcinoma. The receiver operator characteristic (ROC) curve showed that the area for BCL2L10 protein was 0.817 (P=8.331×10(-14)), indicating that loss of BCL2L10 protein expression is an excellent prognostic predictor of gastric carcinoma.
Loss of BCL2L10 protein expression predicts poor clinical outcome in gastric carcinoma.
Histopathology 12/2010; 57(6):814-24. · 3.08 Impact Factor
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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.
Breast Cancer Research and Treatment 05/2010; 126(3):555-63. · 4.43 Impact Factor
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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.
International Journal of Cancer 12/2009; 127(5):1172-9. · 5.44 Impact Factor
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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.
Breast Cancer Research and Treatment 11/2009; 123(2):375-86. · 4.43 Impact Factor
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ABSTRACT: The pathological features of adult-onset Still's disease remain unclear. An original case study of the histopathological changes in various organs of a patient with the disorder is presented. Interstitial inflammation was found in the heart, lung, liver, mucosa of total alimentary canal, and urinary bladder. Previous reports that involved the pathology of visceral organs are also reviewed.
Rheumatology International 10/2009; 31(7):923-7. · 1.88 Impact Factor
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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.
Cancer Science 09/2009; 101(1):80-6. · 3.33 Impact Factor
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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.
Clinical Cancer Research 04/2009; 15(8):2657-65. · 7.74 Impact Factor
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ABSTRACT: The present report concerns an unusual case of extranodal Rosai-Dorfman disease involving the epicardium, mesenterium, pleural cavity and lung. All involved lesions showed characteristics of S100-positive histiocytes exhibiting emperipolesis. The patient was a 51-year-old woman with a 2-year evolution of chest distress, dyspnoea and oedema. Pathological examination indicated that heart failure, which resulted from constrictive pericarditis, led to the fatal outcome of this case. Interference from severe hydropericardium prevented timely diagnosis and appropriate treatment. Therefore it is recommend that, despite being a rare condition, pericardium-involved Rosai-Dorfman disease should be taken into consideration in differential diagnoses, especially in cases of severe hydropericardium.
Case Reports 01/2009; 2009.
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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.
Pathology - Research and Practice 12/2008; 205(2):105-11. · 1.21 Impact Factor
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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.
International Journal of Oncology 12/2008; 33(5):1037-45. · 2.40 Impact Factor
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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.
Chemotherapy 02/2008; 54(4):291-301. · 1.82 Impact Factor
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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;
Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2007; 29(5):355-9.
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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.
Oncology Reports 02/2007; 17(1):261-7. · 1.84 Impact Factor
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ABSTRACT: Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A and p53 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder.
Expressions of the MLH1, MSH2, Aurora-A, and p53 proteins and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17, and 20q13 spots were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry.
The expression levels of the MMR related-proteins decreased in 9 of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group.
The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability.
Clinical Cancer Research 06/2006; 12(9):2752-8. · 7.74 Impact Factor
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ABSTRACT: To clarify the mechanisms underlying cell cycle promotion in malignant germ cell tumours of the ovary (MGCTOs), beta-catenin and components of the pRB pathway, cyclin D1 and p16, were analysed in relation to cell proliferation. Immunohistochemically, p16 protein was not expressed in a number of MGCTOs (9 of 42 tumours: 21.4%) and was associated with p16 gene (INK4A) promoter 5'-CpG islands methylation. Amplification of the cyclin D1 gene (CCND1) was detected in a small number of MGCTOs (5 of 42 tumours: 13.5%). Reduced expression of p16 due to promoter methylation correlated significantly with increased cell proliferation as evidenced by Ki-67 labelling index (p < 0.001) and mitotic index (p < 0.01). In some tumour types, nuclear localization of beta-catenin has been reported to be associated with beta-catenin gene (CTNNB1) mutation, cyclin D1 overexpression, and increased cell proliferation. Nuclear localization of beta-catenin, which was observed in MGCTOs other than dysgerminoma, was not associated with cyclin D1 expression and increased cell proliferation, but appeared to be related to tumour differentiation. Furthermore, CTNNB1 mutations were not detected in any of the MGCTOs examined. Our results suggest that reduced expression of p16 due to INK4A promoter methylation is one of the principal factors that promote cell proliferation in MGCTOs. Thus, p16 may be a novel target for gene therapies to treat MGCTOs.
The Journal of Pathology 12/2004; 204(3):268-76. · 6.32 Impact Factor
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ABSTRACT: The biological behaviors of urothelial carcinomas are linked roughly to histological grade, but there are many cases whose precise classification is difficult. In addition, it remains unclear whether there are differences in the types of genetic changes between low- and high-grade urothelial carcinomas. Fifty-seven biopsy specimens of urothelial carcinomas and 9 control urothelial specimens were examined by four-color FISH with centromere-specific probes for chromosomes 3, 7, and 17, and a locus-specific probe for 9p21 that covers p16INK4a and p15INK4b. Nuclear DNA ploidy was determined with laser scanning cytometry (LSC). FISH and LSC data allowed us to classify urothelial cancers into two groups. Tumors in one group showed minimal intercellular variation in centromere copy numbers and DNA diploidy, and these tumors were histologically comparable to low-grade (grades I and II) tumors. In contrast, tumors in the other group showed a large intercellular variation in centromere copy numbers and DNA aneuploidy, suggesting chromosomal instability. These tumors were all high-grade (grades II and III) tumors. Numerical abnormalities of 9p21 signals were detected in all cancers; this variation in 9p21 signals was also associated with histological grade. The present findings suggest that the pathogenetic pathways are different between low- and high-grade carcinomas. High-grade tumors are characterized by chromosomal instability, whereas low-grade carcinomas are not.
International Journal of Oncology 11/2004; 25(4):893-8. · 2.40 Impact Factor
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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.
International Journal of Oncology 10/2004; 25(3):615-21. · 2.40 Impact Factor
