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Mathilde Guerin,
Chaonan Qian,
Qian Zhong,
Qian Cui,
Yunmiao Guo,
Jinxin Bei,
Jianyong Shao,
Xiaofeng Zhu,
Wenlin Huang,
Jiangxue Wu,
Ranyi Liu,
Qiang Liu,
Jing Wang,
Weihua Jia,
Xiaohui Zheng, Yixin Zeng
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ABSTRACT: Sun Yat-sen University Cancer Center (SYSUCC) is currently conducting many translational studies to improve cancer patients' condition through early diagnosis, discovering new treatments, improving treatment outcomes, and better classification and prognosis of cancer. SYSUCC is a leading institution for treating nasopharyngeal carcinoma (NPC) and carrying out research into the disease. The center has performed several large-scale studies that have produced new insights, such as a genome-wide analysis study, which has allowed researchers to identify new genetic risk factors for NPC; the findings are significant toward building a risk prediction model for NPC. Other researchers are using molecular biological methods to identify new biomarkers, which will allow a better classification and prognosis of this disease. Drug discovery, especially for molecular targeted therapy, is also an active field of research at SYSUCC, not only for NPC treatment, but also for, among others, cancers of the head, neck, and liver. As an alternative to Western medicine, scientists also use derivatives of natural products from Traditional Chinese Medicine to develop new compounds. The tumor biobank at SYSUCC, one of the largest in China, play an essential role in producing clinical applications from research findings. Translational oncology is a promising field, and scientists and clinicians from SYSUCC will continue to work in synergy to develop new anticancer therapies.
Science China. Life sciences 11/2012; · 2.02 Impact Factor
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ABSTRACT: In our previous study, one candidate susceptibility locus for familial nasopharyngeal carcinoma (NPC) has been defined to
a 14.21-cM region on 4p15.1-q12, whereas the distal minimum boundary of this region remained to be further determined in respect
that the two markers D4S2996 and D4S428 were uninformative. In the present study, we carried out a haplotype analysis to identify
the exact boundary by using the combination of a set of microsatellite markers and single nucleotide polymorphism (SNP) markers
in two major NPC families. We defined the exact distal boundary between D4S1577 and D4S3347, and consequently shortened the
susceptibility locus to an 8.29-cM segment on 4p11–p14.
Chinese Science Bulletin 04/2012; 48(21):2328-2331. · 1.32 Impact Factor
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ABSTRACT: Many genes may be involved in nasopharyngeal carcinoma (NPC) development and progression. Several known oncogenes, including
c-myc and c-erb-B2, have been shown to have structural alteration and aberrant expression in NPC. Here, we constructed a tissue microarray to
determine the status of c-myc and c-erbB-2 oncogenes at the DNA and protein levels using interphase fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and to define the diagnostic, prognostic importance of the genetic changes.
Results showed that amplification of c-myc and c-erbB-2 was not found in NPC. Polysomy 8 and 17 were observed in 43%–50% and 20%–27% of NPC tumors, respectively. Overexpressions
of c-myc and c-erbB-2 oncoproteins were detected in 53.6% and 54.5% cases of NPC with polysomy 8 and 17, respectively. There
was no significant correlation between c-myc and c-erbB-2 staining and the clinical stage. But overexpression of c-erbB-2 was associated with polysomy 17 in NPC. These findings suggest that chromosomal polysomy, not gene amplification, may be
partially responsible for the upregulated expression of c-erbB-2 oncogene in NPC.
Chinese Science Bulletin 04/2012; 47(3):218-221. · 1.32 Impact Factor
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ABSTRACT: It has long been suggested that younger women with breast cancer have less favorable prognostic factors and poorer outcomes. Our main objectives were to determine whether poor prognosis among young women was independent of other common clinicopathologic parameters. We retrospectively analyzed 551 young patients (≤ 35 years, Group I) and 551 older patients (36-50 years, Group II), matched for year of diagnosis, family history of breast cancer, pathologic stage, hormone receptor expression and application of adjuvant therapy. Patients in Group I had significantly shorter disease-free survival (DFS) than Group II (median 23.2 months vs. 28.4 months, P = 0.024). Five-year DFS rate(63.7% vs. 74.7%, P < 0.001) and overall survival (OS) rate (79.5% vs. 85.6%, P = 0.024) in Group I was inferior to those in Group II. Multivariate analysis showed that young age was a significantly negative predictor for DFS and OS. Our study thus shows that age (≤ 35 y/o) is an independent risk factor for prognosis in operable breast cancer.
Breast (Edinburgh, Scotland) 08/2011; 20(6):568-73. · 2.09 Impact Factor
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ABSTRACT: The tumor suppressor in lung cancer 1 (TSLC1) has been identified as a putative tumor suppressor gene in non-small cell lung cancer. Although loss of TSLC1 has been observed in a number of human malignancies, the expression levels of TSLC1 gene in ovarian cancer and its clinical or prognostic significance have not been investigated.
Protein expression levels of TSLC1 was explored by semiquantitative immunohistochemical staining on archival formalin-fixed, paraffin-embedded pathological specimen consisting of 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors, and 160 invasive ovarian carcinomas. The TSLC1 immunohistochemical staining results were then correlated with various clinicopathologic parameters and patient prognosis using various statistical models.
Significantly decreased, or complete loss of, protein expression of the TSLC1 gene was observed in 59% ovarian carcinomas, 45% borderline tumors, and 7% cystadenomas, but in none of the normal ovaries (0%). In ovarian carcinomas, decreased TSLC1 expression was significantly correlated with lymph node metastasis (pN, P = 0.001), distant metastasis (pM, P = 0.028), and more advanced International Federation of Gynecology and Obstetrics stages (P = 0.008). By univariate survival analysis on the ovarian carcinoma cohorts, decreased TSLC1 protein expression was significantly associated with shortened patient survival (mean: 26.9 months in tumors with complete loss of TSLC1 vs 63.1 months in tumors with significantly decreased TSLC1 vs 94.3 months in tumors with normal levels of TSLC1; P < 0.001). By multivariate analysis, TSLC1 protein expression remained as a significant and independent prognostic factor for the prediction of patient survival (P = 0.003).
Decreased protein expression of the TSLC1 gene might be important in conferring a more aggressive behavior in ovarian carcinoma. Thus, TSLC1 may be used as an independent prognostic molecular marker for patients with ovarian carcinoma.
International Journal of Gynecological Cancer 04/2011; 21(3):486-93. · 1.65 Impact Factor
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ABSTRACT: The aims of this work were to investigate the antitumor effect of IFNgamma gene transfer on human nasopharyngeal carcinoma (NPC) and to assess the potential of minicircle vector for antitumor gene therapy.
We developed a recombinant minicircle vector carrying the human IFNgamma gene and evaluated the effects of minicircle-mediated IFNgamma gene transfer on NPC cell lines in vitro and on xenografts in vivo.
Relative to p2PhiC31-IFNgamma, minicircle-mediated IFNgamma gene transfer in vitro resulted in 19- to 102-fold greater IFNgamma expression levels in transfected cells (293, NIH 3T3, CNE-1, CNE-2, and C666-1) and inhibited the growth of CNE-1, CNE-2, and C666-1 cells more efficiently, reducing relative growth rates to 7.1 +/- 1.6%, 2.7 +/- 1.0%, and 6.1 +/- 1.6%, respectively. Flow cytometry and caspase-3 activity assays suggested that the antiproliferative effects of IFNgamma gene transfer on NPC cell lines could be attributed to G(0)-G(1) arrest and apoptosis. Minicircle-mediated intratumoral IFNgamma expression in vivo was 11 to 14 times higher than p2PhiC31-IFNgamma in CNE-2- and C666-1-xenografted mice and lasted for 21 days. Compared with p2PhiC31-IFNgamma treatment, minicircle-IFNgamma treatment significantly increased survival and achieved inhibition rates of 77.5% and 83%, respectively.
Our data indicate that IFNgamma gene transfer exerts antiproliferative effects on NPC cells in vitro and leads to a profound antitumor effect in vivo. Minicircle-IFNgamma is more efficient than corresponding conventional plasmids due to its capability of mediating long-lasting high levels of IFNgamma gene expression. Therefore, minicircle-mediated IFNgamma gene transfer is a promising novel approach in the treatment of NPC.
Clinical Cancer Research 09/2006; 12(15):4702-13. · 7.74 Impact Factor
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ABSTRACT: Amplification of SEI-1, a cell cycle regulatory gene at 19q13.1, is commonly detected in ovarian cancer, suggesting a role in the pathogenesis of ovarian cancer. In the present study, the oncogenic potential of SEI-1 was shown by anchorage-independent growth and tumor formation in nude mice with SEI-1-transfected NIH 3T3 mouse fibroblast cells. Silencing of SEI-1 gene expression by small interfering RNAs in ovarian cancer cell line SKOV3 could inhibit cell growth as well as colony formation on soft agar. Chromosomal alterations including the formation of double minutes were observed in tumor cells derived from SEI-1-transformed NIH 3T3 cells. Micronulei formation, which is an indicator of nuclear abnormality and genomic instability, was markedly increased in SEI-1-transfected cells. These data suggest that the oncogenic role of SEI-1 might be mediated at least in part via an effect on genomic instability. Furthermore, overexpression of SEI-1 was associated with higher tumor grades and late Fesddration Internationale des Gynaecologistes et Obstetristes (FIGO) stages in ovarian carcinomas. These data strongly suggest that SEI-1 plays an important role in the development and progression of ovarian cancer.
Cancer Research 09/2005; 65(15):6504-8. · 7.86 Impact Factor
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in southern China, and the genetic susceptibility is believed to play an important role in the aetiology of this malignancy. In our previous studies, one candidate susceptibility locus has been mapped to chromosome 4p11-p14 in a subset of NPC families. In the present study, we screened the cytochrome oxidase VIIb2 (COX7B2) gene which resides in this region and investigated the relationship of single nucleotide polymorphisms (SNPs) of this gene with these familial NPC patients. We identified five novel SNPs in this gene, among them -158101G > T and -157322G > A in promoter region, -109602A > G in intron 2, 78T > A in exon 3, and 354T > A in 3'-untranslational region. The change 78T > A at codon 26 which leads to CAT26CAA (His26Gln) was shared by patients from family 31 that carried the susceptibility haplotype, but not found in cases from other NPC families nor in sporadic cases. However, the frequency of allele A was relatively low in normal controls both from Guangdong and eastern China (0.45% and 0.26%, respectively), and this variant was not found in pooled DNA samples from the white and the black population. Protein sequence alignment showed that the 26His of COX7B2 protein is consistent among different species. Our results suggested that the codon 26 of COX7B2 gene might be conservative during the process of evolution, and the rare variation His26Gln was probably associated with the high risk in NPC pedigree 31.
Science in China Series C Life Sciences 11/2004; 47(5):449-53. · 1.61 Impact Factor
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ABSTRACT: To investigate gene expression profile in nasopharyngeaL carcinoma (NPC) cell lines with different metastatic potentialities, in order to identify new candidate genes related to the development, progress and metastasis of NPC.
The mRNA expressions of high metastatic NPC cell line 5-8F, tumorigenic but nonmetastatic NPC cell line 6-10B and non-tumorigenic NPC cell line 13-9B (3 sublines of SUNE-1) were investigated by cDNA microarray containing 14 000 cDNA clones. The alterations in gene expression levels were confirmed by reverse-transcription PCR.
There were 82 differentially expressed genes comparing 5-8F and 13-9B; 38 differentially expressed genes comparing 6-10B and 13-9B; 54 comparing 5-8F and 6-10B. There were 12 common differentially expressed genes comparing 6-10B, 5-8F and 13-9B; 14 common differentially expressed genes comparing 5-8F and 13-9B, 6-10B. The expressions of the above genes were involved in metabolism, transcription, differentiation, apoptosis and signal transduction.
The gene expression profile in nasopharyngeal carcinoma cell lines is an important index in the search of new candidate genes related to NPC.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 10/2002; 24(5):430-4.
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Jianyong Shao,
Yuhong Li,
Qiuliang Wu,
Xiaoman Liang,
Xingjuan Yu,
Lixi Huang,
Jinghui Hou,
Xiaoming Huang,
Ingemar Ernberg,
Li-Fu Hu, Yixin Zeng
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ABSTRACT: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC.
Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques.
LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells.
Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.
Chinese medical journal 05/2002; 115(4):571-5. · 0.86 Impact Factor
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ABSTRACT: To effectively screen p16 protein expression of different clinical stage nasopharyngeal carcinoma (NPC) by constructing and applying high-throughput tissue microarray/tissue chip.
A series of tissue chips were prepared by using tissue arrayer with samples from different clinical stage NPC tumors and noncancerous nasopharynx tissue. Specimens from 259 cases of nasopharyngeal lesions were detected immunohistochemically on a tissue chip for p16 protein expression and the correlation of p16 protein expression to clinical stage of NPC was analyzed statistically.
p16 protein expression was detected in all 18 histologically normal nasopharyngeal epithelia. No p16 protein was detected in 3 of 3 (100%) stage I NPC, 38 of 44 (86.3%) stage II NPC, 59 of 68 (86.8%) stage III NPC, 23 of 28 (82.1%) stage IV NPC, 87 of 98 (88.8%) unclear stage NPC. The efficiency of p16 protein expression in NPC tissues was significantly lower than that in normal nasopharyngeal epithelia (chi(2) = 82.58, P < 0.001), and there was no apparent relationship between p16 protein expression and clinical stages (chi(2) = 0.09, P = 0.769).
The frequent deletion of p16 protein in NPC suggests that p16 gene has an important role in the development and progression of NPC. The consistency of p16 protein deletion in different stages of NPC suggests that the deletion of p16 protein is an early event in the development of NPC, and it is feasible to utilize tissue microarray for a rapid, economic and accurate screening of clinical tissue specimens on a large scale.
Zhonghua bing li xue za zhi Chinese journal of pathology 05/2002; 31(2):132-4.
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ABSTRACT: Objective: To detect genetic alterations in nasopharyngeal carcinoma (NPC) in Cantonese, the population with the highest incidence
of NPC, and to correlate the findings with clinical staging. Methods: Comparative genomic hybridization (CGH) was performed
on 35 primary nasopharyngeal carcinomas and a nonparametric x2 test was used to analyze relationship between chromosome changes and clinical staging. Results: The identified common chromosomal
alterations in NPC included gain of chromosomes 12q (21 cases, 60%), 4q (19cases, 43%), 3q (18 cases, 51%), 1q (15 cases,
43%),8q (14 cases, 40%), and 2q (12 cases, 30%). The most frequently detected loss of chromosomal materials involved chromosome
1p (24 cases, 69%), chromosome 3p (21 cases, 60%), 11q (20 cases, 57%), 14q (18 cases, 51%), 16q (14 cases, 40%), 13(12 cases,
34%), and 9p(11 cases, 31%). The high frequency (>50%) 4q gain and 1p loss were novel findings. Compared by nonparametric
x2 test, gains on 12q and 8q were found mainly in stages III/IV and there were significant differences between two clinical
stage groups (stages I/II vs stages III/IV). Conclusions: Current analysis has revealed a comprehensive profile of the chromosomal regions showing DNA
copy number changes, which may harbor oncogenes or tumor suppressor genes involved in the development of primary NPC.
Chinese Journal of Cancer Research 01/2001; 13(4):276-279. · 0.18 Impact Factor
