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Featured researches published by Songyin Huang.


Science Translational Medicine | 2012

Targeted delivery of PLK1-siRNA by ScFv suppresses Her2 + breast cancer growth and metastasis

Yandan Yao; Tian-Meng Sun; Songyin Huang; Shuang Dou; Ling Lin; Jianing Chen; Jian-bin Ruan; Cheng-Qiong Mao; Fengyan Yu; Musheng Zeng; Jian-ye Zang; Qiang Liu; Fengxi Su; Peter Zhang; Judy Lieberman; Jun Wang; Erwei Song

Antibody-mediated delivery of anticancer siRNAs suppresses Her2+ breast cancer growth and metastasis. A Bull’s-Eye for Breast Cancer The goal in archery is to hit the center of the target. Although this could be accomplished by randomly shooting a barrage of arrows, it would be more efficient—and less likely to provoke emergency room visits—to aim straight at the bull’s-eye. Cancer therapies work on a similar principle. Broad therapies may treat the cancer but have many unwanted effects on healthy tissue. Yao et al. now target cancer drugs directly to the tumor using single-chain fragmented antibodies (ScFvs). About 60% of metastatic breast cancers that express human epidermal growth factor receptor 2 (Her2) do not respond to the anti-Her2 therapeutic antibody trastuzumab. The authors hypothesized that ScFvs specific to Her2 could deliver small interfering RNA (siRNA) to Her2+ breast cancer cells. They complexed siRNA for Polo-like kinase 1 (PLK1), which promotes cell division, with a Her2-ScFv-protamine peptide fusion protein (F5-P). This complex suppressed Her2+ breast cancer cell lines and primary human cancers in orthotopic breast cancer models. The siRNA complexes slowed tumor cell growth, reduced metastasis, and prolonged survival with no observed toxicity. The antitumor effects were even greater when a mix of siRNAs was delivered. These results suggest that as a new platform to deliver siRNAs to specifically treat Her2+ breast cancers, F5-P may be on target. A major obstacle to developing small interfering RNAs (siRNAs) as cancer drugs is their intracellular delivery to disseminated cancer cells. Fusion proteins of single-chain fragmented antibodies (ScFvs) and positively charged peptides deliver siRNAs into specific target cells. However, the therapeutic potential of ScFv-mediated siRNA delivery has not been evaluated in cancer. Here, we tested whether Polo-like kinase 1 (PLK1) siRNAs complexed with a Her2-ScFv-protamine peptide fusion protein (F5-P) could suppress Her2+ breast cancer cell lines and primary human cancers in orthotopic breast cancer models. PLK1-siRNAs transferred by F5-P inhibited target gene expression, reduced proliferation, and induced apoptosis of Her2+ breast cancer cell lines and primary human cancer cells in vitro without triggering an interferon response. Intravenously injected F5-P/PLK1-siRNA complexes concentrated in orthotopic Her2+ breast cancer xenografts and persisted for at least 72 hours, leading to suppressed PLK1 gene expression and tumor cell apoptosis. The intravenously injected siRNA complexes retarded Her2+ breast tumor growth, reduced metastasis, and prolonged survival without evident toxicity. F5-P–mediated delivery of a cocktail of PLK1, CCND1, and AKT siRNAs was more effective than an equivalent dose of PLK1-siRNAs alone. These data suggest that F5-P could be used to deliver siRNAs to treat Her2+ breast cancer.


PLOS ONE | 2013

miR-150 Promotes Human Breast Cancer Growth and Malignant Behavior by Targeting the Pro-Apoptotic Purinergic P2X7 Receptor

Songyin Huang; Yongsong Chen; Wei Wu; Nengyong Ouyang; Jianing Chen; Hongyu Li; Xiaoqiang Liu; Fengxi Su; Ling Lin; Yandan Yao

The P2X7 receptor regulates cell growth through mediation of apoptosis. Low level expression of P2X7 has been linked to cancer development because tumor cells harboring a defective P2X7 mechanism can escape P2X7 pro-apoptotic control. microRNAs (miRNAs) function as negative regulators of post-transcriptional gene expression, playing major roles in cellular differentiation, proliferation, and metastasis. In this study, we found that miR-150 was over-expressed in breast cancer cell lines and tissues. In these breast cancer cell lines, blocking the action of miR-150 with inhibitors leads to cell death, while ectopic expression of the miR-150 results in increased cell proliferation. We deploy a microRNA sponge strategy to inhibit miR-150 in vitro, and the result demonstrates that the 3′-untranslated region (3′UTR) of P2X7 receptor contains a highly conserved miR-150-binding motif and its direct interaction with miR-150 down-regulates endogenous P2X7 protein levels. Furthermore, our findings demonstrate that miR-150 over-expression promotes growth, clonogenicity and reduces apoptosis in breast cancer cells. Meanwhile, these findings can be decapitated in nude mice with breast cancer xenografts. Finally, these observations strengthen our working hypothesis that up-regulation of miR-150 in breast cancer is inversely associated with P2X7 receptor expression level. Together, these findings establish miR-150 as a novel regulator of P2X7 and a potential therapeutic target for breast cancer.


Oncotarget | 2015

CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer

Ling Lin; Yongsong Chen; Yandan Yao; Jingqi Chen; Jianing Chen; Songyin Huang; Yunjie Zeng; Herui Yao; Si-Hai Zeng; Yong-Shui Fu; Erwei Song

The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3β/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.


PLOS ONE | 2012

HGF-Induced PKCζ Activation Increases Functional CXCR4 Expression in Human Breast Cancer Cells

Songyin Huang; Nengyong Ouyang; Ling Lin; Lili Chen; Wei Wu; Fengxi Su; Yandan Yao; Herui Yao

The chemokine receptor CXCR4 and its ligand CXCL12 have been shown to mediate the metastasis of many malignant tumors including breast carcinoma. Interaction between hepatocyte growth factor (HGF) and the Met receptor tyrosine kinase mediates development and progression of cancers. HGF is able to induce CXCR4 expression and contributes to tumor cell invasiveness in breast carcinoma. However, the mechanism of the CXCR4 expression modulated by c-Met-HGF axis to enhance the metastatic behavior of breast cancer cells is still unclear. In this study, we found that HGF induced functional CXCR4 receptor expression in breast cancer cells. The effect of HGF was specifically mediated by PKCζ activity. After transfection with PKCζ-siRNA, the phosphorylation of PKCζ and CXCR4 was abrogated in breast cancer cells. Interference with the activation of Rac1, a downstream target of HGF, prevented the HGF-induced increase in PKCζ activity and CXCR4 levels. The HGF-induced, LY294002-sensitive translocation of PKCζ from cytosol to plasma membrane indicated that HGF was capable of activating PKCζ, probably via phosphoinositide (PI) 3-kinases. HGF treatment also increased MT1-MMP secretion. Inhibition of PKCζ, Rac-1 and phosphatidylinositol 3-kinase may attenuate MT1-MMP expression in cells exposed to HGF. Functional manifestation of the effects of HGF revealed an increased ability for migration, chemotaxis and metastasis in MDA-MB-436 cells in vitro and in vivo. Our findings thus provided evidence that the process of HGF-induced functional CXCR4 expression may involve PI 3-kinase and atypical PKCζ. Moreover, HGF may promote the invasiveness and metastasis of breast tumor xenografts in BALB/c-nu mice via the PKCζ-mediated pathway, while suppression of PKCζ by RNA interference may abrogate cancer cell spreading.


BMC Infectious Diseases | 2018

Molecular epidemiology and virulence characteristics of Staphylococcus aureus nasal colonization in medical laboratory staff: comparison between microbiological and non-microbiological laboratories

Xiaoying Xie; Xinlu Dai; Lijia Ni; Baiji Chen; Zhaofan Luo; Yandan Yao; Xiquan Wu; Hongyu Li; Songyin Huang

BackgroundMedical laboratory staff are a high-risk population for colonization of Staphylococcus aureus (S. aureus) due to direct and dense contact with the pathogens; however, there is limited information about this colonization. This study sought to determine the prevalence and molecular characteristics of nasal colonization by S. aureus in medical laboratory staff in Guangzhou, southern China, and to compare the differences between microbiological laboratory (MLS) and non-microbiological laboratory (NMLS) staff.MethodsS. aureus colonization was assessed by nasal swab cultures from 434 subjects, including 130 MLSs and 304 NMLSs from 33 hospitals in Guangzhou. All S. aureus isolates underwent the antimicrobial susceptibility test, virulence gene detection and molecular typing.ResultsThe overall prevalence of S. aureus carriage was 20.1% (87/434), which was higher in MLSs than in NMLSs (26.2% vs. 17.4%, P < 0.05), while the prevalence of Methicillin-resistant S. aureus (MRSA) was similar. Living with hospital staff was associated with S. aureus carriage. The majority of the isolates harboured various virulence genes, and those in MLSs appeared less resistant to antibiotics and more virulent than their counterparts. A total of 37 different spa types were detected; among these, t338, t437, t189 and t701 were the most frequently encountered types. T338 was the main spa type contributing to nasal colonization Methicillin-sensitive S. aureus (MSSA) (13.0%), and t437-SCCmec IV was predominant in MRSA isolates (40%).ConclusionsThese findings provide insight into the risk factors, molecular epidemiology and virulence gene profiles of S. aureus nasal carriage among the medical laboratory staff in Guangzhou.


International Journal of Endocrinology | 2017

Bacterial Profile and Antibiotic Resistance in Patients with Diabetic Foot Ulcer in Guangzhou, Southern China: Focus on the Differences among Different Wagner’s Grades, IDSA/IWGDF Grades, and Ulcer Types

Xiaoying Xie; Yunwen Bao; Lijia Ni; Dan Liu; Shaona Niu; Haixiong Lin; Hongyu Li; Chaohui Duan; Li Yan; Songyin Huang; Zhaofan Luo

Objective To understand the bacterial profile and antibiotic resistance patterns in diabetic foot infection (DFI) in different Wagners grades, IDSA/IWGDF grades, and different ulcer types in Guangzhou, in order to provide more detailed suggestion to the clinician about the empirical antibiotic choice. Methods 207 bacteria were collected from 117 DFIs in Sun Yat-sen Memorial Hospital from Jan.1, 2010, to Dec.31, 2015. The clinical data and microbial information were analyzed. Results The proportion of Gram-negative bacteria (GNB) was higher than Gram-positive bacteria (GPB) (54.1% versus 45.9%), in which Enterobacteriaceae (73.2%) and Staphylococcus (65.2%) were predominant, respectively. With an increasing of Wagners grades and IDSA/IWGDF grades, the proportion of GNB bacterial infection, especially Pseudomonas, was increased. Neuro-ischemic ulcer (N-IFU) was more susceptible to GNB infection. Furthermore, with the aggravation of the wound and infection, the antibiotic resistance rates were obviously increased. GPB isolated in ischemic foot ulcer (IFU) showed more resistance than the N-IFU, while GNB isolates were on the opposite. Conclusions Different bacterial profiles and antibiotic sensitivity were found in different DFU grades and types. Clinician should try to stay updated in antibiotic resistance pattern of common pathogens in their area. This paper provided them the detailed information in this region.


Annals of Clinical Microbiology and Antimicrobials | 2018

A case of Cardiobacterium valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation

Lijia Ni; Xiaoying Xie; Nengyong Ouyang; Baiji Chen; Dongye Wang; Xiaoqiang Liu; Xiquan Wu; Jiajian Guo; Hongyu Li; Yandan Yao; Songyin Huang

BackgroundCardiobacterium is a fastidious Gram-negative bacillus, and is a rare human pathogen in clinical settings. Herein, we describe a case of Cardiobacterium valvarum (C. valvarum) endocarditis with a rare complication of cerebral hemorrhage after mitral valve replacement (MVR), tricuspid valve prosthesis (TVP) and vegetation removal operation.Case presentationA 41-year-old woman who had a history of gingivitis developed into infective endocarditis due to the infection of C. valvarum. Then, she was hospitalized to receive MVR, TVP and vegetation removal operation. The indicators of patient tended to be normal until the abrupt cerebral hemorrhage occurred on day 15 after operation. This is the first well-described case of C. valvarum infection in China, and the first report of C. valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation worldwide.ConclusionsWe reported the first case of C. valvarum infection in China clinically, with a rare complication of cerebral hemorrhage after MVR, TVP and vegetation removal operation.


ACS Nano | 2011

Simultaneous Delivery of siRNA and Paclitaxel via a “Two-in-One” Micelleplex Promotes Synergistic Tumor Suppression

Tian-Meng Sun; Jin-Zhi Du; Yandan Yao; Cheng-Qiong Mao; Shuang Dou; Songyin Huang; Pei-Zhuo Zhang; Kam W. Leong; Erwei Song; Jun Wang


BMC Infectious Diseases | 2015

Differences in Staphylococcus aureus nasal carriage and molecular characteristics among community residents and healthcare workers at Sun Yat-Sen University, Guangzhou, Southern China

Baiji Chen; Xinlu Dai; Bo He; Kunyi Pan; Hongyu Li; Xiaoqiang Liu; Yunwen Bao; Weisi Lao; Xiquan Wu; Yandan Yao; Songyin Huang


BMC Infectious Diseases | 2015

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolates collected at a Chinese hospital from 2011 to 2013

Songyin Huang; Xiaoqiang Liu; Weisi Lao; Suhua Zeng; Huiqi Liang; Rihui Zhong; Xinlu Dai; Xiquan Wu; Hongyu Li; Yandan Yao

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Yandan Yao

Sun Yat-sen University

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Hongyu Li

Sun Yat-sen University

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Xiquan Wu

Sun Yat-sen University

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Baiji Chen

Sun Yat-sen University

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Xinlu Dai

Sun Yat-sen University

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Lijia Ni

Sun Yat-sen University

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