Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Xiaoyuan Huang is active.

Publication


Featured researches published by Xiaoyuan Huang.


Journal of Experimental Medicine | 2010

Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion

Xiaoyuan Huang; Xiangyang Bai; Yang Cao; Jingyi Wu; Mei Huang; Duozhuang Tang; Si Tao; Tao Zhu; Yanling Liu; Yang Yang; Xiaoxi Zhou; Yanxia Zhao; Mingfu Wu; Juncheng Wei; Dao Wen Wang; Gang Xu; Shixuan Wang; Ding Ma; Jianfeng Zhou

Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3–expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4+ T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases.


PLOS ONE | 2013

Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis

Yang Cao; Xiaoxi Zhou; Xiaoyuan Huang; Qinlu Li; Lili Gao; Lijun Jiang; Mei Huang; Jianfeng Zhou

Background T cell immunoglobulin mucin-3 (Tim-3) has been identified as a negative regulator of anti-tumor immunity. Recent studies highlight the important role of Tim-3 in the CD8+ T cell exhaustion that takes place in both human and animal cancer models. However, the nature of Tim-3 expression in the tumor cell and the mechanism by which it inhibits anti-tumor immunity are unclear. This present study aims to determine Tim-3 is expressed in cervical cancer cells and to evaluate the role of Tim-3 in cervical cancer progression. Methodology A total of 85 cervical tissue specimens including 43 human cervical cancer, 22 cervical intraepithelial neoplasia (CIN) and 20 chronic cervicitis were involved. Tim-3 expression in tumor cells was detected and was found to correlate with clinicopathological parameters. Meanwhile, expression of Tim-3 was assessed by RT-PCR, Western Blot and confocal microscopy in cervical cancer cell lines, HeLa and SiHa. The migration and invasion potential of Hela cells was evaluated after inhibiting Tim-3 expression by ADV-antisense Tim-3. Conclusions We found that Tim-3 was expressed at a higher level in the clinical cervical cancer cells compared to the CIN and chronic cervicitis controls. We supported this finding by confirming the presence of Tim-3 mRNA and protein in the cervical cell lines. Tim-3 expression in tumor cells correlated with clinicopathological parameters. Patients with high expression of Tim-3 had a significant metastatic potential, advanced cancer grades and shorter overall survival than those with lower expression. Multivariate analysis showed that Tim-3 expression was an independent factor for predicting the prognosis of cervical cancer. Significantly, down-regulating the expression of Tim-3 protein inhibited migration and invasion of Hela cells. Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers.


Biochemical and Biophysical Research Communications | 2008

The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells

Xiaobing Han; Ling Xi; Hui Wang; Xiaoyuan Huang; Xiangyi Ma; Zhiqiang Han; Peng Wu; Xiaoli Ma; Yunping Lu; Gang Wang; Jianfeng Zhou; Ding Ma

Diverse types of voltage-gated potassium (K+) channels have been shown to be involved in regulation of cell proliferation. The maxi-conductance Ca2+-activated K+ channels (BK channels) may play an important role in the progression of human cancer. To explore the role of BK channels in regulation of apoptosis in human ovarian cancer cells, the effects of the specific BK channel activator NS1619 on induction of apoptosis in A2780 cells were observed. Following treatment with NS1619, cell proliferation was measured by MTT assay. Apoptosis of A2780 cells pretreated with NS1619 was detected by agarose gel electrophoresis of cellular DNA and flow cytometry. Our data demonstrate that NS1619 inhibits the proliferation of A2780 cells in a dosage and time dependent manner IC50=31.1 microM, for 48 h pretreatment and induces apoptosis. Western blot analyses showed that the anti-proliferation effect of NS1619 was associated with increased expression of p53, p21, and Bax. These results indicate that BK channels play an important role in regulating proliferation of human ovarian cancer cells and may induce apoptosis through induction of p21(Cip1) expression in a p53-dependent manner.


Clinical Cancer Research | 2005

Novel Oncolytic Adenovirus Selectively Targets Tumor-Associated Polo-Like Kinase 1 and Tumor Cell Viability

Jianfeng Zhou; Qinglei Gao; Gang Chen; Xiaoyuan Huang; Yunping Lu; Kanyan Li; Daxing Xie; Liang Zhuang; Jingniu Deng; Ding Ma

Purpose: Polo-like kinase 1 (plk1) is a serine/threonine protein kinase essential for multiple mitotic processes. Previous observations have validated plk1 as a promising therapeutic target. Despite being conceptually attractive, the potency and specificity of current plk1-based therapies remain limited. We sought to develop a novel plk1-targeting strategy by constructing an oncolytic adenovirus to selectively silence plk1 in tumor cells. Experimental Design: Two artificial features were engineered into one wild-type adenovirus type 5 (wt-Adv5) genome to generate a new oncolytic adenovirus (M1). First, M1 contains a 27-bp deletion in E1A region, which confers potent, oncolytic efficacy. Second, M1 is armed with a fragment of antisense plk1 cDNA that substitutes the E3 region encoding 6.7K and gp19K. In this design, tumor-selective replication of M1 would activate the native adenovirus E3 promoters to express the antisense plk1 cDNA preferentially in tumor cells and silence tumor-associated plk1 protein. Results: By virtue of combining oncolysis with plk1 targeting, M1 exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M1 plus cisplatin induced complete tumor regression in 80% of orthotopic hepatic carcinoma model mice that were otherwise resistant to cisplatin and disseminated metastases. Conclusions: Coupling plk1 targeting with oncolysis had shown superior antitumor efficacy. Present findings would benefit the development of novel oncolytic adenoviruses generally applicable to a wide range of molecule-based therapeutics.


Apoptosis | 2006

Influence of chk1 and plk1 silencing on radiation- or cisplatin-induced cytotoxicity in human malignant cells

Qinglei Gao; Xiaoyuan Huang; Duozhuang Tang; Yang Cao; Gang Chen; Yunping Lu; Liang Zhuang; Shixuan Wang; Gang Xu; Jianfeng Zhou; Ding Ma

The G2/M checkpoint is an attractive pathway for targeting and sensitizing tumor cells to cancer treatment. Abrogation of the G2/M checkpoint by targeting molecules, such as checkpoint kinase 1 (chk1), increases DNA breakage and sensitizes tumor cells to anti-tumoral agents. However, most of the previously described G2/M abrogators are actually targeting the G2-M border checkpoints rather than mitotic checkpoints. This prompted us to test the effects of combined targeting of chk1 and a critical regulator of mitosis, polo-like kinase 1 (plk1). Chk1 and plk1 were found to be co-expressed in 70% of primary neoplastic tissues we examined. Asynchronized tumor cells were treated with different DNA damaging-agents to activate G1/S, S or G2/M checkpoints. Either chk1 or plk1-specific antisense oligodeoxynucleotides (ASODN) enhanced DNA damaging agent-induced apoptosis. When used in combination, however, chk1- plus plk1-specific ASODN failed to produce synergistic effects. Moreover, selective targeting of plk1 or chk1 in tumor xenografts of mice by oncolytic adenovirus mutants demonstrated potent anti-tumoral efficacy in the presence of low dose cisplatin. Again, combined targeting of chk1 and plk1 did not further enhance anti-tumoral efficacy. We concluded that combined targeting of chk1 and plk1 was not superior to either targeting chk1 or plk1 alone, which suggested that chk1 and plk1 silencing might overlap in their mechanism of action. Whether combined targeting of chk1 with other, more specific mitotic regulators would synergistically sensitize tumor to anti-neoplastic therapeutics needs to be further clarified.


International Journal of Gynecological Cancer | 2012

Silencing Wnt2B by siRNA interference inhibits metastasis and enhances chemotherapy sensitivity in ovarian cancer.

Hongyan Wang; Liangsheng Fan; Xi Xia; Yumei Rao; Quanfu Ma; Jie Yang; Yunping Lu; Changyu Wang; Ding Ma; Xiaoyuan Huang

Objective Wnt2B overexpression is thought to be involved in tumor progression through the activation of the canonical Wingless and INT-1 signaling pathway. However, the mechanism of Wnt2B signaling in oncogenesis is unknown. In this study, we investigated whether silencing Wnt2B expression could inhibit the invasiveness of ovarian cancer cells and reduce drug resistance. Methods/Materials Four ovarian carcinoma cell lines, SKOV3, OV2008, A2780, and C13K, were used. Protein levels were studied by Western blotting. The colony formation ability and invasive ability were determined through colony formation assay and the Matrigel transwell assay, respectively. Cell viability was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, whereas apoptosis was assessed using flow cytometry analysis. Results Among the 4 ovarian carcinoma cell lines, the A2780 cells and C13K cells expressed Wnt2B, and these 2 cell lines were used for analyzing the mechanism of Wnt2B. The down-regulation of Wnt2B inhibited cell colony formation and invasiveness. Enhanced paclitaxel or cisplatin sensitivity was observed in A2780 cells or C13K cells treated with Wnt2B siRNA, respectively. In the presence of Wnt2B siRNA treatment, the caspase-9/B-cell lymphoma 2 (BCL2)/B-cell lymphoma-xL (BCL-xL) pathway and the epithelial-mesenchymal transition/phosphorylated protein kinase B pathway were inhibited. Conclusion These data suggest that Wnt2B indeed plays an important role in ovarian cancer metastasis and drug resistance. This study may provide a new therapeutic target for and a better understanding of ovarian cancer therapy.


Molecular Cancer Therapeutics | 2008

Biodistribution and kinetics of the novel selective oncolytic adenovirus M1 after systemic administration

Xiaoyuan Huang; Liang Zhuang; Yang Cao; Qinglei Gao; Zhiqiang Han; Duozhuang Tang; Hui Xing; Wei Wang; Yunping Lu; Gang Xu; Shixuan Wang; Jianfeng Zhou; Ding Ma

Oncolytic adenoviruses represent a promising novel therapeutic option for the treatment of cancer. Despite their demonstrated safety in human clinical trials, the fundamental properties of oncolytic adenovirus biodistribution, spread, viral persistence, and replication in vivo have not been well characterized. The aim of this study was to evaluate the kinetics of viral distribution, spread, replication, and antitumoral efficacy after i.v. administration of a novel oncolytic mutant M1. This mutant consists of the E1A CR2-deleted Adv5 with a fragment of antisense polo-like kinase 1 (plk1) cDNA inserted into the deleted 6.7K/gp19K region, which combines oncolytic properties with efficient plk1 silencing, as described in our previous reports. In the present study, we established a new human orthotopic gastric carcinoma with a high frequency metastasis mouse model and showed that M1 spread not only in local primary tumors but also in disseminated metastases. M1 could effectively replicate in tumor cells leading to “oncolysis” and was able to eliminate expression of the targeted gene plk1 in human orthotopic gastric carcinoma model mice. Therefore, i.v. administration of M1 could prolong the survival time of tumor-bearing mice. [Mol Cancer Ther 2008;7(6):1624–32]


Clinical Cancer Research | 2017

Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

Juncheng Wei; Jie Yang; Dan Liu; Mingfu Wu; Long Qiao; Junnai Wang; Quanfu Ma; Zhen Zeng; Shuangmei Ye; Ensong Guo; Xuefeng Jiang; Lanying You; Ying Chen; Li Zhou; Xiaoyuan Huang; Tao Zhu; Li Meng; Jianfeng Zhou; Zuo-Hua Feng; Ding Ma; Qinglei Gao

Purpose: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. Experimental Design: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. Results: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. Conclusions: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214–24. ©2016 AACR.


International Journal of Oncology | 2011

Suppression of DNA-PKcs and Ku80 individually and in combination: Different effects of radiobiology in HeLa cells.

Liang Zhuang; Yang Cao; Huihua Xiong; Qinglei Gao; Zhe Cao; Fei Liu; Hong Qiu; Shiying Yu; Xiaoyuan Huang

DNA-dependent protein kinase (DNA-PK), including Ku80, Ku70 and DNA-PK catalytic subunit (DNA-PKcs), is the key protein in non-homologous end-joining (NHEJ) after DNA double-strand breaks (DSBs) appear. In this study, small hairpin interfering RNAs (siRNAs) targeting Ku80 and DNA- PKcs were used both individually and in combination, to explore the effects of these DSB proteins on HeLa cell functional changes after X-ray irradiation. HeLa cells co-transfected with Ku80-siRNA and DNA-PKcs-siRNA were more radiosensitive than the ones transfected individually. HeLa in the absence of Ku80 and pretreated with LY294002, a chemically specific PI 3-kinase inhibitor, resulted in cells that were even more sensitive to X-rays than HeLa/Ku80-siRNA transfected with DNA- PKcs-siRNA. The cells inhibited by Ku80 either individually or in combination with DNA-PKcs showed cell accumulation in the G2/M phase 48 h post-irradiation, similarly to control cells. However, cells transfected with DNA-PKcs-siRNA or pretreated with LY294002 had a prolonged G2/M delay, suggesting the accumulation of significant un-repaired DNA damage following inhibition of DSB repair proteins. In conclusion, these data indicate that the role of Ku80 in DSB repair could be compensated by other DSB repair proteins; co-inhibition would be a suitable strategy to enhance the radiosensitivity of cancer cells.


Biochemical and Biophysical Research Communications | 2013

Sema4d is required for the development of the hindbrain boundary and skeletal muscle in zebrafish

Jie Yang; Zhen Zeng; Juncheng Wei; Lijun Jiang; Quanfu Ma; Mingfu Wu; Xiaoyuan Huang; Shuangmei Ye; Ye Li; Ding Ma; Qinglei Gao

Semaphorin4d (SEMA4D), also known as CD100, an oligodendrocyte secreted R-Ras GTPase-activating protein (GAP), affecting axonal growth is involved in a range of processes including cell adhesion, motility, angiogenesis, immune responses and tumour progression. However, its actual physiological mechanisms and its role in development remain unclear. This study has focused on the role of sema4d in the development and expression patterns in zebrafish embryos and the effect of its suppression on development using sema4d-specific antisense morpholino-oligonucleotides. In this study the knockdown of sema4d, expressed at all developmental stages, lead to defects in the hindbrain and trunk structure of zebrafish embryos. In addition, these phenotypes appeared to be associated with the abnormal expression of three hindbrain rhombomere boundary markers, wnt1, epha4a and foxb1.2, and two myogenic regulatory factors, myod and myog. Further, a notable increase of cell apoptosis appeared in the sema4d knockdown embryos, while no obvious reduction in cell proliferation was observed. Collectively, these data suggest that sema4d plays an important role in the development of the hindbrain and skeletal muscle.

Collaboration


Dive into the Xiaoyuan Huang's collaboration.

Top Co-Authors

Avatar

Ding Ma

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Jianfeng Zhou

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Liang Zhuang

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Qinglei Gao

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Yang Cao

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Yunping Lu

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Gang Xu

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Jie Yang

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Juncheng Wei

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Mei Huang

Huazhong University of Science and Technology

View shared research outputs
Researchain Logo
Decentralizing Knowledge