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ABSTRACT: OBJECTIVE: Epithelial ovarian cancer (EOC) remains the most lethal disease among gynecological malignancies. Prompt diagnosis is challenging because of the non-specific symptoms exhibited during the early stage of the disease. As a result, there is an urgent need for improved detection methods. In this study, we established a multiplex methylation-specific PCR (MSP) assay to improve the early detection of ovarian cancer, via identification of the methylation status of cell-free serum DNA. METHODS: After screening, we chose seven candidate genes (APC, RASSF1A, CDH1, RUNX3, TFPI2, SFRP5 and OPCML) with a high frequency of methylation to construct the multiplex-MSP assay. When methylation of at least one of the seven genes was observed, the multiplex-MSP assay was considered positive. We performed retrospective and screening studies to verify the specificity and sensitivity of the assay in the detection of EOC. RESULTS: The methylation status of cell-free serum DNA was examined in the preoperative serum of 202 patients, including 87 EOC patients (stageI,n=41; stageII-IV, n=46), 53 patients with benign ovarian tumors and 62 healthy controls. As expected, the multiplex MSP assay achieved a sensitivity of 85.3% and a specificity of 90.5% in stageI EOC, strikingly higher rates compared with a single CA125, which produced a sensitivity of 56.1% at 64.15% specificity [P=0.0036]. CONCLUSION: A multiplex MSP assay that analyzes the methylation status of cell-free serum DNA is a suitable and reliable approach to improve the early detection of ovarian cancer, potentially benefiting a broad range of applications in clinical oncology.
Gynecologic Oncology 04/2013; · 3.89 Impact Factor
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ABSTRACT: Cervical cancer is the leading cause of death from cancer among women. Radiotherapy for cervical cancer is an effective treatment method; however, the response to radiotherapy varies among patients. Epithelial-mesenchymal transition (EMT) is a morphogenesis process involved in embryonic and organismal development. During tumour progression, EMT may enhance cancer cell invasion, promoting tumour metastasis. We hypothesised that EMT was involved in the enhanced invasiveness of cervical cancer cells after low-dose radiation and aimed to elucidate the underlying mechanism of this process in low-dose radiation of cervical cancer. The irradiated cells (FIR cells) were derived from the parental cells (N cells) with a cumulative dose of 75 Gy. After resting and reorganisation, the effect of low-dose radiation on the FIR cells was analysed. The expression of E-cadherin, N-cadherin and p65 was detected by real-time qPCR and western blotting in parental cancer cells and irradiated cancer cells. Motility was detected using the migration/invasion assay. After silencing of NF-κB p65 expression using siRNA against p65, the expression of E-cadherin and N-cadherin was examined by real‑time qPCR and western blotting. We found that low-dose radiation induced morphological changes of cells. The expression of epithelial markers was downregulated and mesenchymal markers were induced in irradiated cells, both of which are characteristics of EMT. Additionally, in irradiated cells, migration and invasion were enhanced and the expression of p65 was increased. To investigate whether p65 was involved in EMT, we silenced the expression of p65 in irradiated cells using siRNA and found that the features of EMT were suppressed. In summary, p65-regulated EMT induced by low-dose irradiation of cervical cancer cell lines promoted the invasiveness and metastasis of cervical cancer cells. The reversal of EMT may be a new therapeutic target for improving the effectiveness of radiotherapy for cervical cancer.
International Journal of Oncology 03/2013; · 2.40 Impact Factor
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Jintang Sun,
Alei Feng,
Songyu Chen,
Yun Zhang,
Qi Xie,
Meixiang Yang,
Qianqian Shao,
Jia Liu,
Qifeng Yang, Beihua Kong,
Xun Qu
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ABSTRACT: Osteopontin (OPN), a multifunctional glycoprotein, has three transcripts that have distinct roles in tumors in vitro. Whether OPN transcripts have different functions in tumor processes in vivo is unclear. It has been reported that immune cell-derived OPN can promote tumor formation. We propose a hypothesis that tumor-derived OPN may facilitate tumor immune escape by affecting immune cell differentiation and function. In this study, we constructed lentiviral expression vectors of OPN transcripts and transfected them into the MCF-7 cell line. MCF-7 cells transfected with OPN transcripts were injected into the armpit of nude mice, and tumor growth was monitored. The results showed that all OPN transcripts promoted local tumor formation, but that there was no significant difference among transcripts. We also investigated the effect of the OPN expressed by tumor cells on monocyte differentiation by coculturing monocytes with tumor supernatant. We found OPN-c upregulated CD163 levels compared with OPN-a and OPN-b; however, none of the transcripts affected HLA-DR and CD206 levels. All OPN transcripts significantly inhibited TNF-α and enhanced IL-10 production by monocytes. Furthermore, we found that the overexpression of OPN transcripts significantly upregulated TGF-β1 and MCP-1 production by tumor cells. Using neutralizing antibody and recombinant cytokines, we found that OPN overexpressed by tumor cells regulates the production of TNF-α and IL-10 by monocytes partly via MCP-1 and TGF-β1, respectively. Collectively, our results show that OPN transcripts have no distinct role in breast cancer formation in vivo. We also demonstrate that OPN regulates the alternative activation of monocytes via TGF-β1 and MCP-1, which may represent an additional mechanism for tumor immune escape.
Cellular & molecular immunology 03/2013; 10(2):176-82. · 2.99 Impact Factor
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ABSTRACT: Paired-box gene 8 (PAX8) encodes a transcription factor associated with important roles in embryogenesis and disease, and is a member of the PAX gene family. PAX8 has been demonstrated to be crucial in determining cell fate during the development of the thyroid, kidney, brain, eyes and Müllerian system and regulates expression of the Wilms' tumor suppressor gene (WT1). Several previous studies have reported that PAX8 is expressed at high levels in specific types of tumor, including thyroid and renal carcinomas and pancreatic neuroendocrine tumors. In addition, PAX8 has been reported to be useful for the detection and differential diagnosis of ovarian carcinoma. The consistency of PAX8 staining in epithelial ovarian carcinomas (EOCs) and the fallopian tube has provided morphological evidence that EOC may originate from the fallopian tube. The molecular mechanism of PAX8 in the carcinogenesis of these tumors remains unclear and requires further studies.
Oncology letters 03/2013; 5(3):735-738. · 0.11 Impact Factor
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Weiting Gu,
Chenguang Wang,
Weihua Li,
Fu-Ning Hsu,
Lifeng Tian,
Jie Zhou,
Cunzhong Yuan,
Xiao-Jun Xie,
Tao Jiang,
Sankar Addya,
Yanhong Tai, Beihua Kong,
Jun-Yuan Ji
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ABSTRACT: CDK8 is either amplified or mutated in a variety of human cancers, and CDK8 functions as an oncoprotein in melanoma and colorectal cancers. Previously, we reported that loss or reduction of CDK8 results in aberrant fat accumulation in Drosophila and mammals, suggesting that CDK8 plays an important role in inhibiting lipogenesis. Epidemiological studies have identified obesity and overweight as the major risk factors of endometrial cancer, thus we examined whether CDK8 regulates endometrial cancer cell growth by using several endometrial cancer cell lines, including KLE, which express low levels of CDK8, as well as AN3 CA and HEC-1A cells, which have high levels of endogenous CDK8. We observed that ectopic expression of CDK8 in KLE cells inhibited cell proliferation and potently blocked tumor growth in an in vivo mouse model. In addition, gain of CDK8 in KLE cells blocked cell migration and invasion in transwell, wound healing and persistence of migratory directionality assays. Conversely, we observed the opposite effects in all of the aforementioned assays when CDK8 was depleted in AN3 CA cells. Similar to AN3 CA cells, depletion of CDK8 in HEC-1A cells strongly enhanced cell migration in transwell assays, while overexpression of CDK8 in HEC-1A cells blocked cell migration. Furthermore, gene profiling of KLE cells overexpressing CDK8 revealed genes whose protein products are involved in lipid metabolism, cell cycle and cell movement pathways. Finally, depletion of CDK8 increased the expression of lipogenic genes in endometrial cancer cells. Taken together, these results show a reverse correlation between CDK8 levels and several key features of the endometrial cancer cells, including cell proliferation, migration and invasion as well as tumor formation in vivo. Therefore, in contrast to the oncogenic effects of CDK8 in melanoma and colorectal cancers, our results suggest that CDK8 plays a tumor-suppressive role in endometrial cancers.
Cell cycle (Georgetown, Tex.) 03/2013; 12(6). · 5.36 Impact Factor
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ABSTRACT: Leptin overexpression contributes to the tumorigenesis of ovarian cancer. However, the functional mechanism and effects remain unclear. The aberrant expression of tumor-related microRNAs may play an important role in the development of cancer. In this report, we demonstrate that crosstalk between leptin and microRNA-182 and microRNA-96 affects the transformation and proliferation of ovarian cancer cells. Our results showed that leptin enhanced the colony formation of ovarian cancer cells in soft agar. A water-soluble tetrazolium salts assay revealed that leptin promoted ovarian cancer cell (SKOV3 and A2780 cells) proliferation in a time- and dose-dependent manner. The growth effects of leptin on ovarian cancer cells were mediated via the reduced expression of forkhead box O3 and its downstream targets p27 and Bim. We demonstrated that leptin upregulated miRNAs that target forkhead box O3 via luciferase reporter assay. Further examination indicated that only the inhibition of microRNA-182 and/or microRNA-96 rescued the expression of forkhead box O3 inhibited by leptin, and their mimics promoted the proliferation of ovarian cancer cells. Moreover, the signal transducer and activator of transcription 5 pathway, but not the signal transducer and activator of transcription 3 pathway, was implicated in the leptin-mediated expression of microRNA-182 and microRNA-96. In conclusion, our findings suggest that the upregulation of microRNA-182 and microRNA-96 targeting forkhead box O3 plays a significant role in the pro-proliferation effect of leptin on ovarian cancer cells, which might provide preliminary experimental clues for the development of new therapies against ovarian cancer.
The international journal of biochemistry & cell biology 12/2012; · 4.89 Impact Factor
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ABSTRACT: The present study explored the cellular uptake dynamics, the subcellular location and the internalization mechanisms of gold nanoparticles (GNPs) and glucose-capped GNPs (Glu-GNPs). The cancer radiotherapy-enhancing effects of GNPs were also evaluated. We synthesized the GNPs and Glu-GNPs by the seeding technique. The effects on cellular uptake and the radiosensitizing effect induced by GNPs and Glu-GNPs at lower doses were investigated using two human cancer cell lines (HeLa and MCF-7). The intracellular location of the nanoparticles was analyzed by transmission electron microscopy (TEM). Analysis of cellular apoptosis following GNP-based radiotherapy was performed by flow cytometry and TUNEL assay. Cancer cells took up more Glu-GNPs than naked GNPs and the uptake curve showed size- and cell-dependent uptake. GNPs were mainly located in the cytoplasm and endocytosis is the mechanism behind the internalization of GNPs and Glu-GNPs. Lower doses of GNPs and Glu-GNPs still enhanced the killing effect using X-ray irradiation, although the apoptotic rate was not altered. The results presented in this study provide evidence that Glu-GNPs may have a bright future in tumor-targeted diagnosis and treatment.
International Journal of Oncology 11/2012; · 2.40 Impact Factor
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ABSTRACT: OBJECTIVE: p73 and p63 are two structural and functional homologs of p53, and their biological functions in cancer progression have attracted attention due to the presence of variants generated by genetic polymorphisms. Recently, three single nucleotide polymorphisms (SNPs) in the p63 and p73 genes have been associated with female reproduction. In the present study, we aimed to evaluate the relationship between these SNPs and ovarian cancer susceptibility and clinical pathology. METHODS: We genotyped the p63 (rs873330 [Genbank, refSNP ID] T > C [T: original base, C: mutant base]) and p73 (rs4648551 G > A and rs6695978 G > A) SNPs in ovarian cancers and healthy controls and analyzed the distributions of genotype frequencies to evaluate the association of the genotypes with the risk of ovarian cancer and the clinicopathological characteristics. Logistic regression models were applied in statistical analysis. RESULTS: Our research revealed that p73 rs6695978 G > A was significantly associated with ovarian cancer patients. Women with the A allele were at increased risk of ovarian cancer compared to carriers of the G allele (OR = 1.55; 95% CI:1.07--2.19; P = 0.003). Meanwhile, the at-risk A allele was positively related with the occurrence of mucinous ovarian cancer (OR = 3.48; 95% CI:1.15-6.83; P = 0.001), low degree of differentiation (OR = 1.87; 95% CI:1.03-3.47; P = 0.003), lymph node metastasis (OR = 1.69; 95% CI: 1.14-2.75; P = 0.010) and estrogen receptor positive (OR = 2.72; 95% CI: 1.38-4.81; P = 0.002). However, we were unable to find any associations of the polymorphisms in another two SNPs (rs4648551 G > A, rs873330 T > C) with ovarian cancer risk and clinicopathological parameters. CONCLUSIONS: The p73 rs6695978 G > A polymorphism will serve as a modifier of ovarian cancer susceptibility and prognosis. Further investigations with large sample sizes and of the mechanistic relevance of p73 polymorphism will be warranted.
Journal of Experimental & Clinical Cancer Research 10/2012; 31(1):89. · 2.15 Impact Factor
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ABSTRACT: OBJECTIVE: The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo. METHODS: A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot were performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were comparable to those of SKOV3 expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene. RESULTS: The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes. CONCLUSION: These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.
Journal of Experimental & Clinical Cancer Research 09/2012; 31(1):74. · 2.15 Impact Factor
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ABSTRACT: OBJECTIVE: The aim of this study is to evaluate the detection of paired box gene 8 (PAX8) and p53 with immunohistochemistry in pelvic washing cell block sections. METHODS: A total of 92 cases were used in this study, which were assigned to three groups according to the cytopathology files. The first group with positive cytology including endometrial and ovarian carcinomas comprised 32 cases. The second group with suspicious cytology for endometrial or ovarian carcinomas consisted of 29 cases. The third group with negative cytology (regarded as mesothelial cells) included 31 cases. The pelvic washing cell blocks underwent immunohistochemistry to detect PAX8 and p53 expression. RESULTS: Immunoreactivity for PAX8 was found in 75% (24/32) of the cases in the group with positive cytology, in 6.9% (2/29) of the cases with suspicious cytology, and in none of the 31 cases with negative cytology (sensitivity: 75%; specificity: 100%; p<0.05). p53 expression was detected in 37.5% (12/32) of the cases in the first group, in 3.4% (1/29) of the cases in the second group, and in none of the cases in the third group (sensitivity: 37.5%; specificity: 100%; p<0.05). Moreover, the combined expression of PAX8 and p53 showed the same result as the single expression of p53 in the three groups. CONCLUSION: The detection of PAX8 and p53 is beneficial in recognizing metastatic carcinomas in pelvic washings, especially in cases with suspicious cytology, which additionally supports the Müllerian origin of these carcinomas.
Gynecologic Oncology 08/2012; · 3.89 Impact Factor
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ABSTRACT: We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-D-glucose (6-FDG) to gold nanoparticles (6-FDG-GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG-GNPs in vivo using a murine model. At 2 h, following intravenous injection of 6-FDG-GNPs into the murine model, approximately 30% of the 6-FDG-GNPs were distributed to three major organs: the liver, the spleen and the kidney. PEGylation of the 6-FDG-GNPs was found to significantly improve the bio-distribution of 6-FDG-GNPs by avoiding unintentional uptake into these organs, while simultaneously doubling the cellular uptake of GNPs in implanted breast MCF-7 adenocarcinoma. When combined with radiation, PEG-6-FDG-GNPs were found to increase the apoptosis of the MCF-7 breast adenocarinoma cells by radiation both in vitro and in vivo. Pharmacokinetic data indicate that GNPs reach their maximal concentrations at a time window of two to four hours post-injection, during which optimal radiation efficiency can be achieved. PEG-6-FDG-GNPs are thus novel nanoparticles that preferentially accumulate in targeted cancer cells where they act as potent radiosensitizing agents. Future research will aim to substitute the (18)F atom into the 6-FDG molecule so that the PEG-6-FDG-GNPs can also function as radiotracers for use in positron emission tomography scanning to aid cancer diagnosis and image guided radiation therapy planning.
Nanotechnology 08/2012; 23(37):375101. · 3.98 Impact Factor
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ABSTRACT: Recent studies suggest a potential impact of Th17 cells on tumor. In the present study, we investigated the distribution of Th17 cells in relation to Foxp3-expressing T cells in the tumor-infiltrating lymphocytes (TILs) from patients with uterine cervical cancer (UCC), cervical tissues from patients with cervical intraepithelial neoplasia (CIN) and healthy cervical tissues.
Th17 cells and Foxp3-expressing T cells were evaluated by immunohistochemical staining. IL-6, TGF-β, IL-17 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining for microvessel density (MVD) was performed in order to assess the association of IL-17 expression with angiogenesis.
Compared with controls, patients with UCC or CIN had a higher proportion of Th17 cells and Foxp3-expressing T cells, when the ratio of Th17/Foxp3-expressing T cells in TILs was decreased in individual cases, it was more markedly decreased in TILs than normal cervical tissues. Meanwhile, the cytokine(IL-6, TGF-β and IL-10) concentrations were significantly higher in UCC patients than those in healthy controls. Interestingly, the levels of intratumoral Th17 cells were positively correlated with MVD in tumors.
The imbalance of Th17/Foxp3-expressing T cells may play critical roles in the development and progression of UCC and Th17 cells may promote tumor progression by fostering angiogenesis.
Clinica chimica acta; international journal of clinical chemistry 07/2012; 413(23-24):1848-54. · 2.54 Impact Factor
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Weihua Li,
Yanhong Tai,
Jie Zhou,
Weiting Gu,
Zhaofang Bai,
Tao Zhou,
Zhijiu Zhong,
Peter A McCue,
Nianli Sang,
Jun-Yuan Ji, Beihua Kong,
Jie Jiang,
Chenguang Wang
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ABSTRACT: The aberrantly increased lipogenesis is a universal metabolic feature of proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. SREBP1 and its target genes are overexpressed in a variety of cancers; however, the role of SREBP1 in endometrial cancer is largely unknown. We have screened a cohort of endometrial cancer (EC) specimen for their lipogenic gene expression and observed a significant increase of SREBP1 target gene expression in cancer cells compared with normal endometrium. By using immunohistochemical staining, we confirmed SREBP1 protein overexpression and demonstrated increased nuclear distribution of SREBP1 in EC. In addition, we found that knockdown of SREBP1 expression in EC cells suppressed cell growth, reduced colonigenic capacity and slowed tumor growth in vivo. Furthermore, we observed that knockdown of SREBP1 induced significant cell death in cultured EC cells. Taken together, our results show that SREBP1 is essential for EC cell growth both in vitro and in vivo, suggesting that SREBP1 activity may be a novel therapeutic target for endometrial cancers.
Cell cycle (Georgetown, Tex.) 06/2012; 11(12):2348-58. · 5.36 Impact Factor
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ABSTRACT: Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and angiogenesis. Upregulation of MTDH is correlated with both progression and poor clinical outcome of many types of cancers; however, there is currently no information regarding the role of MTDH in radiation sensitivity. Here, we investigated the effects of MTDH on the radiosensitivity of cervical cancer cells using the SiHa cell line. We discovered that cervical cancer cells in which MTDH was knocked down had significantly increased radiosensitivity as measured by a clonogenic assay. MTDH knockdown cells also had increased apoptosis and a decreased proportion of cells arrested in the G2 phase after radiation treatment. MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs) induced by radiation. These results indicate that MTDH affects the radiosensitivity of cervical cancer cells and that MTDH may be a novel target to improve cervical cancer radiation response.
Oncology Reports 05/2012; 27(5):1520-6. · 1.84 Impact Factor
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ABSTRACT: The amplification of oncogenes initiated by high-risk human papillomavirus (HPV) infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC) and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions.
Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH) using chromosome probes to TERC (3q26) and C-MYC (8q24). All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis.
In the normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3) and squamous cervical cancer (SCC) cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC) cases than in the normal and CIN1 cases (p < 0.01). Compared with cytological analysis, the TERC test showed higher sensitivity (90.0% vs. 84.0%) and higher specificity (89.6% vs. 64.3%). The C-MYC test showed lower sensitivity (80.0% vs. 84.0%) and higher specificity (77.7% vs. 64.3%). Using a cut-off value of 5% or more aberrant cells, the TERC test showed the highest combination of sensitivity and specificity. The CIN2+ group showed more high-level TERC gene copy number (GCN) cells than did the normal/CIN1 group (p < 0.05). For C-MYC, no significant difference between the two histological categories was detected (p > 0.05).
The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.
Diagnostic Pathology 04/2012; 7:40. · 1.64 Impact Factor
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ABSTRACT: 53BP1 has been extensively studied as a key component of the DNA damage response, but little is known regarding the role of 53BP1 in preventing tumor development. The present study was designed to assess the impact of the modification of 53BP1 gene expression on the biological behavior of ovarian cancer cell lines and to elucidate the cellular pathway(s) triggered by 53BP1 in cancer cells. DNA liposome transfection technology was employed to increase and to knock down the expression of 53BP1 in A2780 and HO-8910PM cells, respectively. Viability, clonogenicity and cell cycle profiles were evaluated. Cell apoptosis was analyzed using flow cytometric assay. The expression of proteins related to apoptosis and cell signal transduction was assessed using western blotting. Increased expression of 53BP1 decreased the viability and the clonogenicity, and induced G₂/M arrest and apoptosis of the treated cells. The protein expression of Bax, P21 and caspase-3 was upregulated, while the levels of Bcl-2 and p-Akt were reduced to a statistically significant level. In contrast, deregulation of 53BP1 significantly increased proliferative ability. Collectively, our data suggest that 53BP1 is involved in several important steps in controlling cell proliferation and growth and preventing tumor development.
Oncology Reports 04/2012; 27(4):1251-7. · 1.84 Impact Factor
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ABSTRACT: Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine) serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.
Journal of Hematology & Oncology 03/2012; 5:8. · 3.99 Impact Factor
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ABSTRACT: Ovarian carcinoma is a significant cause of cancer mortality in women worldwide. As a heterogeneous disease, distinct clinical and molecular characteristics exist among different histologic subtypes. With the developments in proteomics, surfaced-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is sensitive enough to detect minute quantity of proteins from serum or microdissected cryostat sections. Herein we hypothesized that differentially expressed protein profiles exist in ovarian carcinomas with distinct histologic subtypes. Compared with endometrioid carcinoma, two peaks were significantly higher in serous carcinoma with the m/z of 3622 Da and 4778 Da, reinforcing the need to treat different histologic subtypes of ovarian cancer as different disease entities. Better understanding of these potential diagnostic and therapeutic biomarkers followed with proof-of-target effect will finally contribute to rational combinations of novel therapy and improve individual ovarian cancer patient outcome.
Medical Hypotheses 03/2012; 78(3):407-9. · 1.39 Impact Factor
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ABSTRACT: This study aimed to determine the functional relationship between the levels of dachshund homolog 1 (DACH1) expression and different subtypes of ovarian cancer and to investigate the possible prognostic value of DACH1 in ovarian cancer.
Immunohistochemical staining was deployed to determine the protein levels of DACH1. Staining was performed on patient samples, for whom the detailed follow-up data have been acquired during the last 10 years. Normal, benign, borderline, cancer, and metastatic ovarian cancer samples were included in this study.
The results of our study show that DACH1 protein levels increase with the invasiveness of the ovarian cancer. As the cancer progresses from benign and borderline to metastatic, DACH1 protein expression increases as well. Moreover, with the increase in expression, the subcellular distribution of DACH1 changes from nucleus in normal tissue to cytoplasm in cancer. Finally, DACH1 expression levels were compared with estrogen receptor α (ERα) levels, and the results showed that overall DACH1 levels were higher, whereas also DACH1 exhibited increased cytoplasmic expression in ERα-positive ovarian cancer samples.
These results indicate that DACH1 is highly expressed in metastatic ovarian cancer compared with that of normal, benign, and borderline ovarian tissues and that it could play an important role in cancer growth.
International Journal of Gynecological Cancer 03/2012; 22(3):386-93. · 1.65 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the therapeutic role of systematic retroperitoneal lymphadenectomy in patients with endometrial cancer.
From December 2003 to December 2008, 349 eligible patients who underwent surgical staging procedures at primary treatment were retrospectively analyzed: systematic lymphadenectomy group (n = 246) and no-lymphadenectomy group (n = 103). Survival was analyzed using Kaplan-Meier method and Cox proportional hazards model.
Overall, patients who underwent lymphadenectomy improved 5-year disease-free survival (89.0% versus 80.7%, P = 0.019) and overall survival (92.8% versus 81.5%, P = 0.001) compared to those who did not undergo lymphadenectomy. Overall survival was not related to lymphadenectomy in 212 low-risk patients (93.1% versus 84.6%, P = 0.176). However, this association was found in 137 patients with intermediate and high-risk (86.2% versus 73.3%, P = 0.021). Multivariate Cox regression analysis showed that FIGO stage (P = 0.037) and lymphadenectomy (P = 0.023) were independent prognostic factors for overall survival.
Systematic retroperitoneal lymphadenectomy has a potentially therapeutic role on survival in surgically staged patients with endometrial cancer.
Bulletin du cancer 02/2012; 99(2):E10-7. · 0.67 Impact Factor
