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ABSTRACT: MicroRNA 21 (miR-21) has been implicated in various aspects of carcinogenesis. However, its function and molecular mechanism in cervical squamous carcinoma have not been studied. Using TaqMan quantitative real-time PCR and Northern blot, we confirmed that miR-21 is significantly overexpressed in human cervical squamous cancer tissues and cell lines. Remarkably, we showed that the level of miR-21 correlates with the tumor differentiation and nodal status by ISH. Furthermore, we demonstrated that miR-21 regulates proliferation, apoptosis, and migration of HPV16-positive cervical squamous cells. In order to identify candidate target genes for miR-21, we used gene expression profiling. By luciferase reporter assays, we confirmed that CCL20 is one of its target genes, which is related to the HPV16 E6 and E7 oncogenes. Our results suggest that miR-21 may be involved in cervical squamous cell tumorigenesis.
Biochimica et Biophysica Acta 02/2012; 1822(2):248-60. · 4.66 Impact Factor
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ABSTRACT: ALDH1 has been shown to play a role in the early differentiation of stem cells in some human malignancies. Whether cancer stem cells occur in ALDH1-associated cervical cancer is not known.
We tested the hypothesis that cervical carcinomas contain subpopulations of cells that express ALDH1.The following sources of cervical carcinoma tissues were examined for the presence of stem cell marker ALDH1 by immunohistochemistry. Flow cytometric isolation of cancer cells was based on enzymatic activity of ALDH (Aldefluor assay). The mRNA and protein levels of ALDH1 were investigated by qRT-PCR and Western blot, respectively. We also detected the expression of CD133 identified as a stem cell marker for several cancers.
23/89 samples of invasive squamous carcinoma and 4/20 samples of adenocarcinomas exhibited immunoreactivity to stem cell marker aldehyde dehydrogenase 1 (ALDH1). Expression of ALDH1 was found in 24.77% of the samples. Flow cytometric analysis, qRT-PCR and Western blot also confirmed the presence of small subpopulations of ALDH1-positive cells. In contrast, we found cervical carcinoma had low CD133 population.
Cervical carcinoma contains a small subpopulation of cells that may relate to a cancer stem cell-like phenotype, ALDH1.
Medical science monitor: international medical journal of experimental and clinical research 08/2011; 17(8):HY21-26. · 1.70 Impact Factor
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ABSTRACT: It has been well established that the aberrant activation of the Wnt/β-catenin signal correlates to endometrial endometrioid adenocarcinoma (EEC). As an effector of the Wnt/β-catenin mediated antiapoptotic signal, the role of Wnt-induced secreted protein-1 (WISP-1) in EEC still remains unclear.
We used immunohistochemistry and quantitative real-time RT-PCR to examine the expression of WISP-1, the estrogen receptor (ER) and progesterone receptor (PR) in 86 cases of EEC, with 20 cases of endometrial hyperplasia, 20 of proliferative endometrium and 20 of secretory endometrium used as the control group. We also correlated the expression of WISP-1 with various clinicopathologic factors and prognostic values in patients with EEC.
A high expression of WISP-1 was observed in 26 of the 86 cases of EEC (30.2%). The expression rate of WISP-1 in EEC was significantly higher than that in secretory endometrium (P < 0.005). Histopathological grades and PR were associated with high WISP-1 expression (P = 0.002, P = 0.027, respectively). The estimated five-year survival rate of patients with low-to-moderate expression of WISP-1 was significantly higher than those with high WISP-1 expression (91.3% vs 65%, P = 0.011). Multivariate analysis revealed that high WISP-1 expression and positive lymphovascular space invasion were independent prognostic factors for survival.
High expression of WISP-1 was related to tumor cell dedifferentiation and PR loss. WISP-1 might be a new molecular marker to predict the prognosis of patients with EEC.
Journal of Obstetrics and Gynaecology Research 06/2011; 37(6):606-12. · 0.94 Impact Factor
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Medical Oncology 04/2011; · 2.14 Impact Factor
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ABSTRACT: Because altered microRNAs (miRNAs) expression patterns have been observed in a variety of diseased tissues, miRNA expression was compared in human cervical cancer tissues relative to adjacent normal cervical tissues in the present study. Microarray chips with 924 probes were used to detect the expression of miRNAs in cervical cancer tissue and adjacent normal cervical tissue of 13 patients with cervical cancer (11 squamous cervical cancers, one cervical adenocarcinoma, and one cervical sarcoma), all of whom were infected with human papilloma virus (HPV) 16 and/or HPV18. Compared to the expression levels in normal cervical tissues, 18 miRNAs (1.9%) were significantly upregulated (increase of ≥2×), and 19 miRNAs (2.1%) were significantly downregulated (decrease of ≤0.5×) in cervical cancer tissues. miRNA expression was independent of lymph node involvement, vascular invasion, and pathological differentiation. Taken together, cervical cancer tissues have altered expression of miRNAs relative to adjacent normal tissues. Further studies are necessary to determine whether aberrant miRNA expression is related to the pathogenesis of cervical cancer.
Medical Oncology 01/2011; 29(2):1242-8. · 2.14 Impact Factor
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ABSTRACT: To study the feasibility and outcome of functional reconstruction during radical abdominal trachelectomy in the treatment of early stage cervical carcinoma.
Ten cervical cancer patients (FIGO stage IA2 or IB1 with tumours less than 2 cm in diameter) who desired to preserve their fertility underwent abdominal radical trachelectomy with functional reconstruction, including preserving the ascending uterine artery, placing a stent to avoid intrauterine adhesions and using three pieces of mesh to prevent cervical incompetence and uterine prolapse.
The mean age of the patients was 29 years (range 28-30). The average operative time was 261 min (range 204-345), with a mean blood loss of 370 ml (range 150-500). The mean time to remove the urinary catheter was 12 days (range 8-14) after surgery and the mean time to remove pelvic drainage was 4 days (range 2-8). During the follow-up (range 4-68 months), no recurrence was detected and a normal menstrual pattern resumed within 8 weeks after surgery. No abnormality was noted in the preserved ascending branches of the uterine arteries, and no intrauterine adhesion was found. One patient successfully conceived without reproductive assistance and another patient conceived with in vitro fertilization. There was no cervical incompetence or premature rupture of membrane in their pregnancies, and cesarean sections were done as in normal women at a gestation of 38(+5) weeks and 34(+3) weeks, respectively.
We conclude that the functional reconstruction is a good choice of fertility-sparing surgery for patients with early stage cervical carcinoma.
European journal of obstetrics, gynecology, and reproductive biology 03/2010; 151(1):77-81. · 1.97 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are small noncoding RNAs of 19-24 nucleotides in length and involved in gene expression regulation. They are associated with cell proliferation, differentiation, apoptosis, and carcinogenesis. The specific expression profiles of miRNAs have been found in many human cancers, but there are few studies on endometrioid adenocarcinoma. We found the miRNA expression profile in 10 pairs of endometrioid adenocarcinoma and adjacent nontumorous endometrium using human miRNA microarray. Seventeen miRNAs exhibited higher expression and six miRNAs exhibited lower expression in endometrioid adenocarcinoma samples than those in the nontumorous samples in the microarray. Of those, the miR-205, miR-449, and miR-429 were greatly enriched; in contrast the miR-204, miR-99b, and miR-193b were greatly downregulated in adenocarcinoma tissues. The expressions of these six miRNAs were validated using real time reverse transcription-PCR. This information may provide the candidate miRNA genome for further confirming the role of miRNAs in carcinogenesis of endometrioid adenocarcinoma and potentially serving as a diagnostic or therapeutic tool in endometrioid adenocarcinoma.
European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 03/2009; 18(1):50-5. · 2.21 Impact Factor
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ABSTRACT: Cervical cancer (CC) is closely associated with the human papillomavirus (HPV). Although most patients are able to clear the infection over time, some eventually develop cancer, suggesting the existence of other factors that determine malignant progression. Such factors may include genetic susceptibility. To determine whether human leukocyte antigen (HLA) class II is related to CC among Han race population in the Guangdong region of China, HLA class II typing were carried out by polymerase chain reaction in 126 patients with CC and 88 selected controls. The allele and haplotype frequencies in both the study and control groups were calculated. The occurrence of DPB1 *1301 [odds ratio (OR), 2.66; 95% confidence interval (CI), 1.12-6.29], DPB1 *0202 (OR, 3.65; CI, 1.04-12.80), DQB1 *030302(OR, 1.85; CI, 1.04-3.27), and DQB1 *050301(OR, 3.94; CI, 1.48-10.46) alleles were more common in the study group than control. This suggests that these alleles may confer susceptibility to CC in the Guangdong Province. In a similar fashion, the occurrence of DRB1 *13-DQB1 *06 (OR, 0.17; 95% CI, 0.04-0.80) haplotype was significantly lower in the study patients compared with the controls and may confer a decreased risk of CC among Han race population in the Guangdong Province of China.
Cancer genetics and cytogenetics 01/2009; 187(2):95-100. · 1.54 Impact Factor
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ABSTRACT: Human leukocyte antigen (HLA) class II alleles have been associated with an increased or decreased risk of developing cervical cancer through infection with oncogenic forms of human papillomavirus (HPV). To verify whether HLA class II allelic polymorphism is related to cervical cancer in China, 133 cervical cancers and 98 healthy controls were analyzed for HLA typing. Our results showed that DPB1*1301 allele frequency was significantly higher in the cervical cancers compared with healthy controls (OR, 3.793; p = 0.002; Pc = 0.04). A significant relationship was found between DRB1*150101-DQB1*0602 haplotype (OR, 0.180; p < 0.0001; Pc < 0.003), DRB1*070101-DQB1*0201 haplotype (OR, 0.110; p = 0.001; Pc = 0.03), and decreased risk for cervical cancer. Similar tendencies were observed for DRB1*150101-DQB1*0602 haplotype with HPV16 positive cervical cancers (OR, 0.182; p = 0.001; Pc = 0.021), and for DRB1*070101-DQB1*0201 haplotype (OR, 0.144; p =0.003; Pc = 0.063). These results indicate that HLA-DPB1*1301 may confer susceptibility to cervical cancer, and the haplotypes DRB1*150101-DQB1*0602 and DRB1*070101-DQB1*0201 may contribute to the resistance to the development of cervical cancer among Chinese women. The study suggests that specific HLA class II alleles and haplotypes may influence the immune response to specific HPV-encoded epitopes and affect the risk of cervical cancer in a Chinese population from an area with a high incidence of this neoplasia.
Human Immunology 03/2007; 68(3):192-200. · 2.84 Impact Factor
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Yuping Wu,
Yulong Chen,
Longyu Li,
Yicheng Cao,
Zehuan Liu,
Benrong Liu,
Zhengping Du,
Yanling Zhang,
Shangwu Chen, Zhongqiu Lin,
Anlong Xu
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ABSTRACT: Cervical cancer is strongly associated with the infection by oncogenic forms of human papillomavirus (HPV). Although most women are able to clear HPV infection, some develop persistent infections that may lead to cancer, implying genetic susceptibility factors for malignant progression. To verify whether HLA class II DQB1 polymorphism is related to cervical cancer in Chinese population, HLA-DQB typing was carried out by PCR-SBT for 258 patients with cervical cancer and 284 healthy controls, and the allele frequencies were calculated. In this study, HLA-DQB1*060101 and DQB1*0602 alleles were significantly higher in the HPV16 infected patients with cervical cancer compared with healthy controls (chi(2) = 31.7452, p < 0.0001; chi(2) = 12.7838, p(c) = 0.0066), but DQB1*050201 allele was significantly lower (chi(2) = 26.2187, p < 0.0001). This result indicates that HLA-DQB1*060101 and DQB1*0602 may confer susceptibility to cervical cancer, and DQB1*050201 may contribute to the resistance to the development of cervical cancer among Chinese women. Sequence analysis reveals that DQB1*060101 allele encodes Leu at position 9 and Asp at position 37, unique to the susceptibility to cervical cancer, whereas the other DQB1 alleles encode Phe or Tyr and Ile or Tyr at the same two positions, respectively. This finding implies that polymorphic amino acids at the putative antigen binding residues 9 and 37 of HLA-DQB1 alleles may play an important role in the development of cervical cancer.
International Journal of Cancer 07/2006; 118(12):3006-11. · 5.44 Impact Factor
