Xingsheng Yang

University of Jinan (Jinan, China), Chi-nan-shih, Shandong Sheng, China

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Publications (13)29.8 Total impact

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    ABSTRACT: Photothermal ablation (PTA) is a promising avenue in the area of cancer therapeutics that destroys tumor cells through conversion of near-infrared (NIR) laser light to heat. Hollow gold nanospheres (HGNs) are one of the few materials that are capable of converting light to heat and have been previously used for photothermal ablation studies. Selective delivery of functional nanoparticles to the tumor site is considered as an effective therapeutic approach. In this paper, we demonstrated the anti-cancer potential of HGNs. HGNs were conjugated with monoclonal antibody (anti-TROP2) in order to target cervical cancer cells (HeLa) that contain abundant trophoblast cell surface antigen 2 (TROP2) on the cell surface. The efficient uptake and intracellular location of these functionalized HGNs were studied through application of inductively coupled plasma atomic emission spectroscopy (ICP-AES) and transmission electron microscopy (TEM). Cytotoxicity induced by PTA was measured using CCK-8 assay. HeLa cells incubated with naked HGNs (0.3–3 nmol L−1) within 48 h did not show obvious cytotoxicity. Under laser irradiation at suitable power, anti-TROP2 conjugated HGNs achieved significant tumor cell growth inhibition in comparison to the effects of non-specific PEGylated HGNs (P < 0.05). γH2AX assay results revealed higher occurrences of DNA-DSBs with anti-TROP2 conjugated HGNs plus laser radiation as compared to treatment with laser alone. Flow cytometry analysis showed that the amount of cell apoptosis was increased after laser irradiation with anti-TROP2 conjugated HGNs (P < 0.05). Anti-TROP2 conjugated HGNs resulted in down-regulation of Bcl-2 expression and up-regulation of Bax expression. Our study results confirmed that anti-TROP2 conjugated HGNs can selectively destroy cervical cancer cells through inducing its apoptosis and DNA damages. We propose that HGNs have the potentials to mediate targeted cancer treatment.
    Nanotechnology 08/2014; 25(34):345103. · 3.84 Impact Factor
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    ABSTRACT: The objective of this study was to illustrate the role of enhancer zeste homolog 2 (EZH2) overexpression in the proliferation, progression, and prognosis of cervical cancer. We detected EZH2 and Ki-67 expression levels using immunohistochemical (IHC) studies in 20 normal cervical tissues, 50 cervical intraepithelial neoplasia (including 25 low-grade intraepithelial lesions and 25 high-grade intraepithelial lesions), and 101 cervical cancer tissues. The relationships between EZH2 expression and Ki-67 expression, conventional clinicopathologic characteristics of cervical cancer, and patient outcomes were evaluated. The effect of EZH2 expression on cancer-specific survival was assessed by multivariate Cox regression analysis. Positive expression of EZH2 was detected in 10% (2/20) of the normal cervical tissues, 52% (13/25) of the low-grade squamous intraepithelial lesions, 64% (16/25) of the high-grade squamous intraepithelial lesions, and 68.3% (69/101) of the cervical cancer tissues. The expression of Ki-67 was positively correlated with EZH2 expression: 5% (1/20) in normal cervical tissues, 48% (12/25) in low-grade squamous intraepithelial lesions, 52% (13/25) in high-grade squamous intraepithelial lesions, and 57.4% (58/101) in cervical cancer tissues. Overexpression of EZH2 was adversely associated with clinical stage, histologic differentiation, infiltration depth, and lymph node metastasis (P<0.05). Patients with EZH2-positive expression showed a decreased overall survival compared with those with EZH2-negative expression (P=0.003, log-rank test). Multivariate Cox regression analysis suggested that overexpression of EZH2 was an independent predictor of poor prognosis in cervical cancer. Overexpression of EZH2 was closely associated with the carcinogenesis, proliferation, clinical and biologic behaviors, and the prognosis of cervical cancer, suggesting that it might be used as a potential predictor of prognosis in cervical cancer.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2014; · 2.07 Impact Factor
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    ABSTRACT: To evaluate the impact of ovarian preservation on overall survival in young women with early-stage endometrial cancer. Retrospective and meta-analysis. Two medical centers. A total of 203 patients diagnosed with endometrial cancer (≤45 years) from 2000 until 2010. Patients who underwent oophorectomy versus those whose ovaries were preserved. The overall survivals were compared. Independent factors that may affect the patients' survival were extracted and analyzed. A meta-analysis of the literature was carried out to further validate the findings. Of 203 young patients, 169 patients (83.3%) underwent bilateral salpingo-oophorectomy, 20 patients had both ovaries preserved, and 14 patients had a single ovary preserved. Multivariate logistic regression identified intraoperative extrauterine disease as the most significant risk factor of ovarian involvement. A Kaplan-Meier curve and Cox proportional hazards models analyses found that ovarian preservation had no effect on overall survival. The findings were validated by meta-analysis. Ovarian preservation has no statistically significant impact on the overall survival of young patients with early-stage endometrial cancer. The ovaries should be preserved in this specific population after a thorough preoperative evaluation and an extensive intraoperative exploration.
    Fertility and sterility 07/2013; · 3.97 Impact Factor
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    ABSTRACT: PRMT5 has been reported to be involved in the processes of tumor progression at various steps. The aim of this study was to examine the role of PRMT5 in epithelial ovarian cancer (EOC). In this study, PRMT5 and Ki-67 expression were examined by immunohistochemistry (IHC) in cohorts of normal, benign, and cancerous ovarian tissues. PRMT5 overexpression was observed in 83.1% (98/118) of EOCs, and it was significantly associated with serous type, poor differentiation, advanced tumor stage, lymph node invasion, presence of residual tumor, and high expression of Ki-67 (p<0.05, respectively). Moreover, overexpression of PRMT5 was an independent prognostic marker for decreased overall survival and progression-free survival in univariate survival analysis and multivariate Cox regression analysis. In ovarian cancer cell lines A2780 and SKOV3, PRMT5 knockdown by siRNA inhibited cell growth/proliferation and induced apoptosis via upregulation of E2F-1. These results suggest that overexpression of PRMT5 correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for EOC. Thus, PRMT5 may represent a clinically effective new target for therapy of ovarian cancer.
    Journal of Histochemistry and Cytochemistry 01/2013; · 2.26 Impact Factor
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    ABSTRACT: Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poor prognosis in a variety of human cancers, however the roles of TROP2 in cervical cancer have not been investigated. The purpose of our study was to elucidate the prognostic significance of TROP2 expression in patients with cervical cancer and determine its effect on tumor progression. Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer specimens were positively stained with TROP2, and the overexpression of TROP2 was closely related with FIGO stage, histological grades, lymphatic metastasis, invasive interstitial depth and high expression of Ki-67. Patients with TROP2-positive staining exhibited a significantly decreased overall survival and progression free survival; it was also an independent predictor for prognosis according to multivariate analysis. Moreover, down-regulation of TROP2 mediated by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1 arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells remarkably promoted cell growth, migration and invasion. In addition, the tumorigenic function of TROP2 was associated with the increased expressions of cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin. The present study suggest that overexpression of TROP2 may play crucial roles in the development and pathogenesis of human cervical cancer, therefore, TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer.
    PLoS ONE 01/2013; 8(9):e75864. · 3.73 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. · 3.07 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. · 0.61 Impact Factor
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    ABSTRACT: The purpose of this study is to determine the methylation status of Transforming growth factor-beta-inducible gene-h3 (TGFBI) and its correlation with paclitaxel chemoresistance in ovarian cancer. The methylation status of TGFBI was examined in ovarian cancer and control groups by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). The TGFBI expression and cell viability were compared by Quantitative Real-Time PCR, Western Blotting and MTT assay before and after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment in 6 cell lines (SKOV3, SKOV3/TR, SKOV3/DDP, A2780, 2780/TR, OVCAR8). In our results, TGFBI methylation was detected in 29/40 (72.5%) of ovarian cancer and 1/10 (10%) of benign ovarian tumors. No methylation was detected in normal ovarian tissues (P < 0.001). No statistical correlation between RUNX3 methylation and clinicopathological characteristics was observed. A significant correlation between TGFBI methylation and loss of TGFBI mRNA expression was found (P < 0.001). The methylation level of TGFBI was significantly higher in paclitaxel resistant cell lines (SKOV3/TR and 2780/TR) than that in the sensitive pairs (P < 0.001). After 5-aza-dc treatment, the relative expression of TGFBI mRNA and protein increased significantly in SKOV3/TR and A2780/TR cells. However, no statistical differences of relative TGFBI mRNA expression and protein were found in other cells (all P > 0.05), which showed that re-expression of TGFBI could reverse paclitaxel chemoresistance. Our results show that TGFBI is frequently methylated and associated with paclitaxel-resistance in ovarian cancer. TGFBI might be a potential therapeutic target for the enhancement of responses to chemotherapy in ovarian cancer patients.
    Journal of Experimental & Clinical Cancer Research 01/2012; 31:6. · 3.07 Impact Factor
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    ABSTRACT: Differentiating embryonic stem (ES) cells are an increasingly important source of hematopoietic progenitors, useful for both basic research and clinical applications. To date, characteristics of specific factors capable of influencing hematopoietic cell fate from ES cells remains elusive. We report that mMSC Feeder Layer and the combination of VEGF, SCF and TPO strongly promote hematopoietic differentiation. The results showed that the cells induced from ES-D3 expressed hematopoietic progenitor antigens (CD34 and CD117), myelocyte cell antigen (CD11b), erythrocyte cell antigen (Ter119), and transcription factors (Flk-1, GATA-2, SCL, beta-H1 and beta-major). Furthermore, those induced differentiated cells were injected into female C57BL/6 mice which were treated with high dose topotecan chemotherapy to restore part of their blood system function. We observed rapid white blood cell recovery, which suggested that the infusion of differentiated cells has a positive impact on hematopoiesis. The Sry gene in peripheral blood, bone marrow and spleen of transplanted female mice was confirmed by PCR analysis, which affirmed the existence of the chimera.
    Journal of chemotherapy (Florence, Italy) 07/2005; 17(3):302-8. · 0.83 Impact Factor
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    ABSTRACT: To investigate the anti-tumor effect of anti-MUCI single-chain variable fragment (ScFv)-targeted and lentivirus-mediated herpes simplex virus structural protein VP22 and thymidinre kinase (TK) therapy on MUC1(+) human ovarian epithelial carcinoma tumor in mice transplanted intraperitoneally. Lentiviruses scFv-VP22-TK and VP22-TK were constorted Ten female BABL/c mice were injected intraperitoneally with MUC1+ human ovarian epithelial carcinoma cells line 3AO and then pathological examination was done to those mice that died of tumor. A human ovarian epithelial carcinoma model was established in another 30 female mice and they were randomly divided into 6 groups of 5 mice: NS (normal saline) + NS group (injected intraperitoneally with NS once per day for 3 days and then with NS 24 h after once a day for 5 days), VP22-TK + NS group (injected with herpes simplex virus structural protein VP22 and TK once a day for three days and then with NS 24 h after once a day for 5 days), scFv-VP22-TK + NS group (injected with scFv-VP22-TK and then NS in the same way), NS + ganciclovir (GCV) group (injected with NS and then with GCV), VP22-TK + GCV group (injected with VP22-TK and then GCV), and scFv-VP22-TK + GCV group (injected with scFv-VP22-TK and then GCV). The survival time was observed. Ten female nude mice without injection of tumor cells were injected with scFv-VP22-TK or VP22-TK, each for 5 mice; 3 weeks later their abdominal organs were examined to observe the effects of lentivirus on organs. All of the first ten mice injected with human ovarian epithelial carcinoma cells died of tumor. The mean survival times of the six experimental groups were 18.4 d +/- 2.9 d, 18.8 d +/- 1.5 d, 17.6 d +/- 1.1 d, 18.5 d +/- 1.6 d, 24 d +/- 5 d, and 46 d +/- 22 d respectively with significant differences between the VP22-TK + GCV group and NS + GCV group (chi(2) = 6.71, P = 0.009), between the scFv-VP22-TK + GCV group and NS + GCV group (chi(2) = 9.7, P = 0.002), and between the scFv-VP22-TK + GCV group and the VP22-TK + GCV group (chi(2) = 7.43, P = 0.006). Necrosis and apoptosis could be seen in the tumors in the VP22-TK + GCV group and scFV-VP22-TK + GCV group. No toxicity was observed in the mice injected with only scFv-VP22-TK or VP22-TK. The anti-MUCI ScFv-targeted and lentivirus-mediated herpes simplex virus VP22 and thymidinre kinase (TK) gene therapy has a significant anti-tumor effect on MUC1+ human ovarian epithelial carcinoma.
    Zhonghua yi xue za zhi 10/2002; 82(17):1207-10.
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    ABSTRACT: The aims of this retrospective study by means of immunohistochemical staining were (1) to study the expression of c-ras, c-erbB-2, p53, and nm23 gene products in complete hydatidiform moles that progress to gestational trophoblastic tumor and in those that remit spontaneously after evacuation, and (2) to estimate the predictive value of the expression of these four gene products in malignant transformation of complete hydatidiform mole. Clinical data of patients with complete hydatidiform mole were obtained by retrospective chart review. Formalin-fixed paraffin sections of 50 cases of complete mole that progressed to gestational tumor and 32 cases of complete mole that remitted spontaneously were studied immunohistochemically for c-ras, c-erbB-2, p53, and nm23 proteins. The prognostic value of the proteins for the malignant transformation of complete mole was analyzed by multiple logistic regression and stepwise logistic estimation. Sections of 30 cases of invasive mole and 19 cases of choriocarcinoma were also immunohistologically studied for expression of the proteins. Expression of c-erbB-2 and p53 gene products was significantly increased and expression of nm23 and c-ras products was remarkably decreased in complete hydatidiform moles that progressed into postmolar tumor compared with those that remitted spontaneously after evacuation. There was no significant difference in the expression of the four genes in invasive mole and in choriocarcinoma. A logistic estimation model for predicting malignant transformation of complete mole was established based on the expression of gene products. When the expression of four gene products was used, the predictive sensitivity of the regression model was 86.0%, and the specificity was 75.0%. The positive predictive value was 84.3%, the negative predictive value was 77.4%. Logistic stepwise regression analysis showed that the altered expression of c-erbB-2 and nm23 products had strong predictive value, while the expression of c-ras and p53 products had no significant predictive value for the malignant transformation of complete mole. The altered expression of c-ras, c-erbB-2, nm23, and p53 gene products may be important in the pathogenesis of gestational trophoblastic tumor. The decreased expression of nm23 protein and increased expression of c-erbB-2 protein are strong predictors for the malignant transformation of complete mole.
    Gynecologic Oncology 07/2002; 85(3):438-44. · 3.93 Impact Factor
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    ABSTRACT: Calcineurin B homologous protein isoform 2 (CHP2) was identified to be expressed in various malignant cell lines including ovarian cancer, but not in the normal tissue counterpart. The biological function of CHP2 related to cancer progression is still unknown. A CHP2-negative human epithelial ovarian cancer cell line OVCAR3 was used for this study. CHP2 was analyzed before and after gene transfection. Cell proliferation, adhesion, motility, and invasion capacities were assessed in parental and transfected OVCAR3/CHP2 cell lines to explore the possible functions of CHP2 in ovarian cancer progression. With RT-PCR analysis, CHP2-transfected OVCAR3/CHP2 cancer cells showed high CHP2 gene expression, whereas non-transfected clones did not produce detectable CHP2 mRNA. CHP2-transfected OVCAR3/CHP2 cells showed increased proliferation rates and exhibited increased activities of cell adhesion, migration and invasion. The current study provides the first evidence that overexpression of the CHP2 gene affects the biological behavior of ovarian cancer cell line OVCAR3 and is one of key mechanisms for ovarian carcinoma progression, suggesting that CHP2 may be an attractive target for biological anticancer therapy.
    In vivo (Athens, Greece) 21(4):593-8. · 1.22 Impact Factor
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    ABSTRACT: Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive, HIV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK, followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). CONCLUSION: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.
    In vivo (Athens, Greece) 17(2):153-6. · 1.22 Impact Factor