Publications by authors named "Hailing Tang"

30 Publications

  • Page 1 of 1

CD52 Is a Prognostic Biomarker and Associated With Tumor Microenvironment in Breast Cancer.

Front Genet 2020 2;11:578002. Epub 2020 Nov 2.

Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Tumor microenvironment (TME) plays an essential role in the development and metastasis of breast cancer (BC). More studies are needed on the differences and functions of immune components and matrix components. In this study, we calculated the proportion of tumor-infiltrating immune cells (TICs) and the proportion of immune and matrix components of BC patients from The Cancer Genome Atlas (TCGA). We performed Cox regression analysis and constructed protein-protein interaction (PPI) network based on the differentially expressed genes (DEGs) and obtained the most crucial gene . CD52 significantly upregulated and affected the prognosis of BC patients. Gene set enrichment analysis (GSEA) suggested that the genes in the CD52 high-expression group were mainly enriched in immune-related pathways, while those in the CD52 low-expression group were mainly enriched in metabolic pathways. TICs analyses showed that there should be a positive correlation between CD52 expression and CD8+ T cells, activated memory CD4+ T cells, macrophage M1, and Gamma Delta T cells. It indicated that CD52 might be an essential factor in maintaining the immune-dominant position of TME. These results suggest that CD52 might be a potential biomarker for prognosis and provide a new therapeutic target for BC patients.
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http://dx.doi.org/10.3389/fgene.2020.578002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667128PMC
November 2020

Suppression of FAK by nexrutine inhibits gastric cancer progression.

Life Sci 2020 Sep 14;257:118100. Epub 2020 Jul 14.

Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, PR China.

Aim: Nexrutine, an herbal extract of Phellodendron amurense, has been found to play a tumor-suppressive role in many cancers. However, its role in the pathogenesis of gastric cancer remains unclear.

Materials And Methods: Gastric cancer cells (SGC-7901 and MGC-803) were treated with nexrutine, and cell proliferation, invasion and apoptosis were analyzed. And the MGC-803 cells-derived xenograft mouse models were fed pelleted diet containing 600 mg/kg nexrutine for 21 days after inoculation. Mechanically, we focused on the influences of nexrutine on the levels and activation of STAT3 and NF-κB as well as their upstream regulator FAK. Additionally, we further verified whether nexrutine affected the proliferation, invasion and apoptosis of gastric cancer cells via FAK by upregulating FAK expression before nexrutine treatment.

Key Findings: We found nexrutine inhibited the viability, invasion, and expression levels of PCNA, CyclinD1 and Bcl-2, promoted the apoptosis and Bax expression, decreased levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, FAK and phospho-FAK in gastric cancer cells. Overexpression of FAK reversed the impacts of nexrutine on the levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, as well as the malignant characteristics of gastric cancer cells. Moreover, nexrutine suppressed tumor volumes and weights, and decreased expression and phosphorylation of FAK, STAT3 and NF-κB p65 in vivo.

Significance: Nexrutine inhibited the malignant progression of gastric cancer via negatively regulating STAT3/NF-κB signaling pathway by suppressing FAK expression and activation.
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http://dx.doi.org/10.1016/j.lfs.2020.118100DOI Listing
September 2020

Endoscopic papillectomy of benign papillary tumors: A single-center experience.

Medicine (Baltimore) 2020 May;99(22):e20414

Department of Gastroenterology, Changhai Hospital, Changhai Road 168, Shanghai.

Endoscopic treatment of duodenal papillary tumors is well described. This study aims to provide new evidence for the treatment of benign papillary tumors through comparisons between endoscopic snare papillectomy (ESP) and endoscopic mucosal resection (EMR).Between May 2010 and December 2017, 72 patients were enrolled. Diagnosis and treatment procedures were ESP and EMR. Endoscopic follow-up evaluation was done periodically as a surveillance measurement for recurrence.Seventy-two patients with ampullary tumors were enrolled, of which 66 had adenomas including 9 high-grade intraepithelial neoplasias and 2 carcinomas in adenoma. Complete resections with tumor-free lateral and basal margins were achieved in all patients. Postoperative complications were bleeding (9.5% in EMR vs 10% in ESP) and pancreatitis (2.4% in EMR and 3.3% in ESP), with no occurrence of perforation, cholangitis or papillary stenosis. Adenoma recurrence was found in 7 patients (14.3% in EMR vs 3.3% in ESP) at 1 year.The ESP procedure is safe and effective for benign ampullary adenoma, high-grade intraepithelial neoplasias, and noninvasive cancer without intraductal tumor growth, which has a shorter procedural duration, as well as lower complication, recurrence rates and hospitalization costs.
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http://dx.doi.org/10.1097/MD.0000000000020414DOI Listing
May 2020

Silencing DVL3 defeats MTX resistance and attenuates stemness via Notch Signaling Pathway in colorectal cancer.

Pathol Res Pract 2020 Aug 25;216(8):152964. Epub 2020 Apr 25.

Department of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710061, PR China. Electronic address:

Chemoresistance and recurrence of colorectal cancer are mainly caused by the existence of cancer stem-like cells. Dishevelled-3 (DVL3) is a common member of both Wnt/β-catenin pathway and the Notch signaling pathway, which were involved in cancer progression, chemoresistance and even maintenance of stem cell-like properties. However, the underlying biological function of DVL3 still remains unclear. In this study, we proposed DVL3 was simultaneously involved in Methotrexate (MTX) resistance and Colorectal cancer (CRC) stemness by bioinformatic analysis. We also demonstrated DVL3 knockdown sensitized CRC cells to MTX and inhibited their stem cell-like properties by functional experiments. As for the mechanism, DVL3 silencing attenuated the activated Notch signaling by down-regulating Notch intracellular domain (NICD) as well as its downstream targets. Additionally, we demonstrated that CRC cancer tissues had greater DVL3 expression than adjacent non-cancer tissues and patients' overall survival was closely associated with DVL3 according to the data in our clinical center. Accordingly, our data suggest that DVL3 is a key regulator in CRC stemness and chemoresistance and targeting DVL3 could be a potential strategy for CRC therapy.
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http://dx.doi.org/10.1016/j.prp.2020.152964DOI Listing
August 2020

Reimaging biological barriers affecting distribution and extravasation of PEG/peptide- modified liposomes in xenograft SMMC7721 tumor.

Acta Pharm Sin B 2020 Mar 2;10(3):546-556. Epub 2019 Jul 2.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery.
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http://dx.doi.org/10.1016/j.apsb.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049609PMC
March 2020

Genetic alteration profile of -mutant resected IIB-IIIA stage NSCLC and correlation to clinical outcomes.

Transl Lung Cancer Res 2019 Dec;8(6):838-846

Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China.

Background: Genetic alteration profile of epidermal growth factor receptor () mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out.

Methods: Clinicopathological and follow-up information were collected for 99 -mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform.

Results: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). and were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of (P=0.021), (P=0.002), (P<0.001), (P=0.015), (P=0.042), (P=0.006), and wildtype (P=0.032), (P=0.012), (P=0.035) were independent risk factors for the recurrence of resected mutant NSCLC.

Conclusions: and was the most common concurrent mutant driver gene. Mutations of , and wildtype were independent risk factors for the recurrence of resected mutant NSCLC.
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http://dx.doi.org/10.21037/tlcr.2019.10.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976375PMC
December 2019

miR-665 promotes the progression of gastric adenocarcinoma via elevating FAK activation through targeting SOCS3 and is negatively regulated by lncRNA MEG3.

J Cell Physiol 2020 05 24;235(5):4709-4719. Epub 2019 Oct 24.

Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Studies have found that miR-665 acted as a tumor suppressor or an oncogene in different malignancies. miR-665 expression was elevated in gastric adenocarcinoma tissues; however, its role and mechanism in this disease are not fully clarified. The expression of miR-665 and its target gene was detected in human gastric adenocarcinoma tissues and cells. Moreover, we analyzed the effects of miR-665 on the proliferation, migration, and epithelial-mesenchymal transition (EMT) of gastric adenocarcinoma cells as well as tumor growth in vivo. The mechanisms of miR-665 in gastric adenocarcinoma were investigated by using molecular biology techniques. We found miR-665 was upregulated and suppressor of cytokine signaling 3 (SOCS3) was downregulated in gastric adenocarcinoma tissues and cells. Elevated miR-665 was positively correlated with tumor size, lymph node metastasis, invasion depth, TNM stage, and poor differentiation in gastric adenocarcinoma patients. Overexpression of miR-665 promoted, whereas knockdown of miR-665 suppressed the proliferation, migration, and EMT of gastric adenocarcinoma cells. Furthermore, we demonstrated that miR-665 functioned through targeting SOCS3, followed by activation of the FAK/Src signaling pathway in gastric adenocarcinoma cells. miR-665 antagomir inhibited tumor growth as well as the activation of the FAK/Src pathway but increased SOCS3 expression in nude mice. In addition, miR-665 expression was negatively regulated by long noncoding RNA maternally expressed gene 3 (MEG3). In conclusion, miR-665 acted as an oncogene in gastric adenocarcinoma by inhibiting SOCS3 followed by activation of the FAK/Src pathway and it was negatively modulated by MEG3. miR-665 may be a promising therapeutic target for the treatment of gastric adenocarcinoma.
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http://dx.doi.org/10.1002/jcp.29349DOI Listing
May 2020

Next generation sequencing-based molecular profiling of lung adenocarcinoma using pleural effusion specimens.

J Thorac Dis 2018 May;10(5):2631-2637

The Translational Medicine Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: Molecular profiling of non-small cell lung cancer (NSCLC) is essential for therapeutic decision-making. Pleural effusion obtained by a non-invasive, repeatable procedure may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we aimed to evaluate the diagnostic performance of pleural effusion as a specimen for molecular analysis.

Methods: Thirty patients with paired malignant pleural effusion and thoracic biopsy specimens were included. Clinically actionable mutations were assessed using a validated targeted next generation sequencing assay. mutation status in thoracic biopsy specimens was tested using ARMS PCR.

Results: The concordance rate between gene status identified by ARMS and next-generation sequencing (NGS) analysis in the thoracic biopsy and pleural effusion samples was 86.7% (26/30). Compared with the thoracic biopsy specimens, the diagnostic performance of pleural effusion showed a sensitivity of 92.3%, a specificity of 50.0%, and a positive predictive value of 92.3%. Therefore, cases with a low percentage of tumor cells (<5%) can successfully be used to detect actionable mutations in pleural effusion specimens.

Conclusions: These results suggest that pleural effusions are suitable specimens for oncogene mutation analysis and enable targeted therapy for patients with advanced NSCLC.
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http://dx.doi.org/10.21037/jtd.2018.04.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006135PMC
May 2018

Comprehensive targeted super-deep next generation sequencing enhances differential diagnosis of solitary pulmonary nodules.

J Thorac Dis 2018 Apr;10(Suppl 7):S820-S829

The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.

Background: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed.

Methods: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach.

Results: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3.9%. The first innovative whole mutation scored model in this study predicted 33.3% of malignant SPN with 100% specificity.

Conclusions: These results showed that lung cancer gene-targeted deep capture sequencing is not efficient enough to achieve ideal sensitivity by simply increasing the sequencing depth of ctDNA from early candidates. The sequencing could not be evaluated hotspot mutations in the early tumour stage. Nevertheless, a larger cohort is required to optimize this model, and more techniques may be incorporated to benefit the SPN high-risk population.
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http://dx.doi.org/10.21037/jtd.2018.04.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945686PMC
April 2018

Microbial infection pattern, pathogenic features and resistance mechanism of carbapenem-resistant Gram negative bacilli during long-term hospitalization.

Microb Pathog 2018 Apr 13;117:356-360. Epub 2018 Feb 13.

Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China; Centre for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China. Electronic address:

Background: Carbapenem-resistant Gram-negative bacilli (GNB) have become an important cause of nosocomial infections of hospitalized patients.

Methods: To investigate the microbial infection patterns and molecular epidemiology characteristics of the carbapenem-resistant GNB isolates from a long-term hospitalized patient, antimicrobial susceptibility testing, phenotypic screening test for carbapenemase production, PCR screening and DNA sequencing of carbapenemase genes, repetitive extragenic palindromic sequence-based PCR (REP-PCR), multilocus sequencing typing (MLST) and genetic environment analysis were performed.

Results: Twelve strains with carbapenemase genes were detected from 63 carbapenem-resistant isolates, including two bla-carrying Pseudomonas aeruginosa, one bla-carrying Citrobacter freundii, three bla-carrying Klebsiella pneumoniae and six bla-carrying K. pneumoniae. Only the bla genes were successfully transferred from three K. pneumoniae strains to Escherichia coli C600 by conjugation. Genetic environment of bla, bla and bla genes in our study were consistent with previous reports. Molecular typing of K. pneumoniae performed by MLST revealed that most of the isolates belonged to ST11. bla-carrying K. pneumoniae sequencing type 1416 was first reported in our study.

Conclusions: Carbapenem-resistant GNB are common pathogens during long-term hospitalization, and ST11 bla-carrying K. pneumoniae is the dominant bacterium in our study. Colonization and horizontal transmission of resistance by plasmids of carbapenem-resistant GNB have increased the risks of persistent infection and mortality of long-term hospitalized patients.
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http://dx.doi.org/10.1016/j.micpath.2018.02.025DOI Listing
April 2018

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Genes Chromosomes Cancer 2018 04 30;57(4):211-220. Epub 2018 Jan 30.

State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, 510120, China.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors. In this study, we developed a next-generation sequencing (NGS)-based test for the detection of clinically relevant mutations in ctDNA and evaluated the feasibility of using this ctDNA NGS-based assay as an alternative to tissue genotyping. Tissue and matched blood samples were obtained from 72 patients with advanced nonsmall cell lung cancer (NSCLC). NGS-based testing was performed using plasma cell-free DNA (cfDNA) samples of all 72 patients as well as tumor DNA samples of 46 patients. Of the remaining 26 patients, tDNA was tested by amplification refractory mutation system PCR (ARMS-PCR) because of insufficient tissue sample or quality for NGS. Of the 46 patients who had tDNA and cfDNA NGS performed, we found 20 patients were concordant between tDNA and ctDNA alterations and 21 sample pairs were discordant because of additional alterations found in tDNA. Considering all clinically relevant alterations, the concordance rate between tDNA and ctDNA alterations was 54.9% with a sensitivity of 53.2% and a specificity of 75.0%. Our findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.
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http://dx.doi.org/10.1002/gcc.22522DOI Listing
April 2018

Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients.

Cancer Sci 2017 Dec 20;108(12):2487-2494. Epub 2017 Oct 20.

State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, China.

People of East Asian ethnicity have a different prevalence of and show unique clinical characteristics and tumor histology of oncogenic mutations. However, only limited studies have explored the landscape of genomic alterations in lung adenocarcinoma derived from Asian patients thus far. In this single-center study, with an aim to elucidate the mutational profile of lung cancer in people of Chinese ethnicity and to use the obtained information to guide decision-making for treatment, we employed a well-validated assay to perform comprehensive genomic characterization of tumor specimens from 306 Chinese lung cancer patients. A total of 845 individual genomic alterations were found in 145 tumor-related genes with a median of 2.8 alterations (range: 1-18) per sample. The most frequently mutated genes were EGFR (46.7%), TP53 (21.2%), ALK (12.1%; 8.8% of mutation and 3.3% of rearrangement) and KRAS (10.1%). Upon comparison with the Cancer Genome Atlas dataset, we found that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS was only found in 10.1% of our Chinese patients. Clinically relevant genomic alterations were identified in 185 (60.5%) patients, including 50% in adenocarcinoma patients and 14% in squamous cell carcinoma patients. Our findings suggest that the Asian ethnicity is significantly different from the Caucasian ethnicity with regard to the presence of somatic driver mutations. Furthermore, we showed that the use of a comprehensive genotyping approach could help identify actionable genomic alterations that have potential impact on therapeutic decisions.
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http://dx.doi.org/10.1111/cas.13410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715245PMC
December 2017

UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in Asians with Lung Cancer: a meta-analysis.

Cancer Chemother Pharmacol 2017 Jun 13;79(6):1109-1117. Epub 2017 May 13.

Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, No 151, Yanjiang Rd, Guangzhou, 510120, Guangdong, People's Republic of China.

Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in Asians with lung cancer remains controversial. In this meta-analysis, we found a higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a weak correlation with diarrhea, but no significant correlation with neutropenia. Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR. These data suggest that the UGT1A1*28 polymorphism may not be a suitable biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia and diarrhea, but not IRI-based chemotherapy TR.
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http://dx.doi.org/10.1007/s00280-017-3306-9DOI Listing
June 2017

Gastrin induces multidrug resistance via the degradation of p27Kip1 in the gastric carcinoma cell line SGC7901.

Int J Oncol 2017 Jun 4;50(6):2091-2100. Epub 2017 May 4.

Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.

Multidrug resistance (MDR) is one of the major reasons for the failure of chemotherapy-based gastric carcinoma (GC) treatments, hence, biologically based therapies are urgently needed. Gastrin (GAS), a key gastrointestinal (GI) hormone, was found to be involved in tumor formation, progression, and metastasis. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining analysis revealed a high level of expression of GAS in drug-insensitive GC tissues (P<0.01) and similar results were revealed in GC cell lines SGC7901 and its multidrug-resistant variants SGC7901/VCR and SGC7901/ADR. We constructed a eukaryotic expression vector pCDNA3.1(+)/GAS for GAS overexpression and recombinant lentiviral vectors for specific siRNA (siGAS). Transfection of pCDNA3.1(+)/GAS increased (P<0.05) while transfection of siGAS (P<0.05) and co-treated with paclitaxel (TAX) and vincristine (VCR) combination (TAX-VCR) decreased (P<0.01) the cell viability of SGC7901, SGC7901/VCR and SGC7901/ADR. Apoptosis rates of SGC7901/VCR and SGC7901/ADR were reduced by pCDNA3.1(+)/GAS and increased by siGAS (P<0.05). The apoptosis rates of SGC7901/VCR, SGC7901/ADR and SGC7901 were all upregulated (P<0.01) when cells were co-treated with a combination of siGAS and TAX-VCR. Additionally, siGAS significantly downregulated the expression of Bcl-2 and multidrug-resistant associate protein (MRP1) and P-glycoprotein (Pgp) (P<0.05) in SGC7901/VCR and SGC7901/ADR cells. Moreover, GAS overexpression in SGC7901 cells significantly inhibited p27Kip1 expression but increased phosphorylation levels of p27Kip1 on Thr (187) and Ser (10) sites (P<0.05), as well as increasing nuclear accumulation of S-phase kinase-associated protein 2 (Skp2) and cytoplasmic accumulation of the Kip1 ubiquitination-promoting complex (KPC) (P<0.05). Silencing of Skp2 blocked the promoting effects of pCDNA3.1(+)/GAS on viability, the expression of MRP1 and Pgp and the inhibitory effects of pCDNA3.1(+)/GAS on apoptosis. In conclusion, we suggest that GAS contributes to the emergence of MDR of SGC7901 cells via the degradation of p27Kip1.
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http://dx.doi.org/10.3892/ijo.2017.3983DOI Listing
June 2017

Gastrin Enhances Autophagy and Promotes Gastric Carcinoma Proliferation via Inducing AMPKα.

Oncol Res 2017 Sep 5;25(8):1399-1407. Epub 2017 Jan 5.

Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells, and it also plays a vital role in the development and progression of GC. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating GC tumorigenesis. Gastrin-17 amide (G-17) was applied in the GC cell lines SGC7901 and MGC-803. The results showed that G-17 maintained the high viability of SGC7901 and MGC-803. The expression of autophagy marker proteins LC3II and Beclin1 was significantly increased, while the autophagy substrate p62 was obviously decreased in the gastrin group compared with the control group. Moreover, G-17 strengthened the expressions of AMPKα, Ras, Raf, MEK, and ERK1/2. Additionally, administration of AMPKα siRNA counteracted the effect of gastrin in SGC7901 cells. Finally, in an in vivo study of the tumor growth and survival rate of rats, the levels of AMPKα/Ras/Raf/MEK/ERK were significantly increased in the gastrin group and decreased following AMPKα shRNA injection. In conclusion, these findings indicate that gastrin plays a tumorigenic role by promoting autophagy in GC and may provide a novel therapeutic target for GC treatment.
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http://dx.doi.org/10.3727/096504016X14823648620870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841241PMC
September 2017

EGFR gene copy number as a predictive/biomarker for patients with non-small-cell lung cancer receiving tyrosine kinase inhibitor treatment: a systematic review and meta-analysis.

J Investig Med 2017 01 23;65(1):72-81. Epub 2016 Sep 23.

Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and China State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Epidermal growth factor receptor (EGFR) gene copy number has been proposed as a candidate biomarker for predicting treatment response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). MEDLINE, PubMed, Cochrane, and Google Scholar databases were searched until October 21, 2015 using the following search terms: lung neoplasms/lung cancer/non-small cell lung cancer/NSCLC, EGFR, gene amplification, copy number, erlotinib, gefitinib, tyrosine-kinase inhibitor/TKI, predictor. 17 studies were included in the analysis with a total of 2047 patients. The overall analysis found that increased EGFR gene copy number was associated with higher overall response rate (ORR), overall survival (OS) and progression-free survival (PFS; p values ≤0.008) compared with patients without a high EGFR gene copy number. Subgroup analysis found that in a population of patients who were primarily Caucasian, a higher EGFR gene copy number was also associated with increased ORR, OS, and PFS (p values ≤0.018). The results were similar in a population of Asian patients, except that a higher EGFR gene copy number was not associated with improved OS (p=0.248). Sensitivity analysis indicated that no one study overly influenced the results and that the findings are robust. The result of the analysis found that EGFR gene copy number was associated with increased OS and PFS, supporting the idea that EGFR gene copy number is a biomarker for response to EGFR-TKI therapy in patients with advanced NSCLC.
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http://dx.doi.org/10.1136/jim-2016-000252DOI Listing
January 2017

GABRA3 promotes lymphatic metastasis in lung adenocarcinoma by mediating upregulation of matrix metalloproteinases.

Oncotarget 2016 May;7(22):32341-50

Southern Medical University, Guangzhou, China.

Tumor metastasis is the main reason for the poor prognosis of lung cancer patients. The GABAA receptor subunit GABRA3 is reportedly upregulated in lung cancer. Herein, we show that high GABRA3 protein expression in lung adenocarcinoma correlated positively with disease stage, lymphatic metastasis status and poor patient survival. In addition, GABRA3 induced MMP-2 and MMP-9 expression through activation of the JNK/AP-1 signaling pathway, which enhanced lymphatic metastasis by lung adenocarcinoma both in vitro and in vivo. These results indicate that GABRA3 promotes lymph node metastasis and may thus be an effective therapeutic target for anticancer treatment.
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http://dx.doi.org/10.18632/oncotarget.8700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078017PMC
May 2016

Up-Regulation of Plasma miR-23b is Associated with Poor Prognosis of Gastric Cancer.

Med Sci Monit 2016 Feb 2;22:356-61. Epub 2016 Feb 2.

Division of Gastroenterology, The Second Affiliated Hospital Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland).

Background: Gastric cancer (GC) is a common malignant disease and microRNAs (miRNAs) have been shown to play important roles in GC tumorigenesis. As the clinical outcome of GC is closely correlated with the clinical stage at the time of diagnosis, early detection and prevention are crucial. This study was designed to evaluate the expression level of plasma miR-23b in patients with GC and investigate the relationship between plasma miR-23b expression level and the prognosis of GC.

Material/methods: We recruited 138 patients diagnosed with GC and 50 healthy volunteers. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression level of plasma miR-23b in all participants. The association between miR-23b expression and clinicopathological factors as well as survival rates was analyzed. Receiver operator curve (ROC) analysis was carried out to evaluate the diagnostic performance of plasma miR-23b for GC.Univariate and multivariate Cox regression analyses were conducted to determine whether plasma miR-23b was an independent predictor of survival.

Results: The expression levels of miR-23b were upregulated in plasma samples from GC patients (P<0.01) and were significantly associated with T stage, distant metastasis, and differentiation. Significantly shorter 5-year overall survival (OS) and disease-free survival (DFS) were observed in patients with higher expression of the miR-23b (P<0.01). The area under the curve (AUC) of high expression of plasma miR-23b to diagnose GC was 0.80 (95% CI: 0.74-0.86, P<0.001). Multivariate analysis revealed that enhanced expression of plasma miR-23b was an independent predictor of OS (P=0.015) and DFS (P=0.004).

Conclusions: Our results indicated that plasma miR-23b was overexpressed in GC patients and high plasma miR-23b expression was associated with poor clinical outcome. Thus, plasma miR-23b may serve as a potential diagnostic biomarker and therapeutic target for GC.
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http://dx.doi.org/10.12659/msm.895428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745659PMC
February 2016

Pleural fluid carcinoembryonic antigen as a biomarker for the discrimination of tumor-related pleural effusion.

Clin Respir J 2017 Nov 25;11(6):881-886. Epub 2016 Jan 25.

Department of Cardiothoracic Surgery, Guangzhou Institute of Respiratory Disease, State Key Laboratary of Respiratory Disease, The First Hospital Affiliated to Guangzhou Medical University, Guangzhou, 510120, Guangdong Province, China.

Objectives: To assess the value of tumor biomarkers in the determination of tumor-related pleural effusion (PE). Cytological examination of the pleural fluid has a limited sensitivity in diagnosing tumor PE.

Methods: Pleural fluid and serum samples were obtained from 1137 patients and PE etiology was determined by multiple diagnostic techniques. Carcinoembryonic antigen (CEA) levels were measured in both pleural fluid and serum samples. Levels of cancer antigen (CA) 125, glucose, and lactate dehydrogenase (LDH) were assessed in pleural fluid specimens.

Results: 601 PE patients were diagnosed with tumors, while 595 tested individuals were tumor-free. Among the measured biomarkers, pleural fluid CA 125, glucose, and LDH levels, and serum CEA amounts were comparable between tumor and tumor-free PE patients (P > 0.05). Only pleural fluid CEA levels were significantly different between the two groups (P < 0.05). A CEA cutoff of 2.645 ng/mL yielded sensitivity and specificity of 69.4% and 82.2%, respectively, for tumor-related PE detection. The area under the curve for CEA was 0.740 (95%CI: 0.710-0.770).

Conclusion: CEA levels in pleural fluid were a potential biomarker for the detection of tumor-related PE. These findings provide an easy and simple method for clinical screening and detection of PE.
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http://dx.doi.org/10.1111/crj.12431DOI Listing
November 2017

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.

Nat Commun 2015 Dec 9;6:10131. Epub 2015 Dec 9.

Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.
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http://dx.doi.org/10.1038/ncomms10131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682110PMC
December 2015

Targeting and liposomal drug delivery to CD40L expressing T cells for treatment of autoimmune diseases.

J Control Release 2015 Jun 1;207:86-92. Epub 2015 Apr 1.

School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China. Electronic address:

CD40L is considered as an important target for the treatment of autoimmune diseases. There have been many efforts devoted to the development of antibodies and other molecules to disrupt CD40/CD40L interaction for therapeutic benefits. In this study, we designed a CD40L specific peptide ligand - A25 based on CD40L crystal structure and molecular docking studies. Its binding affinity and specificity to CD40L were confirmed by Surface Plasmon Resonance (SPR) measurements. The peptide A25 was then conjugated on the surface of liposomes and shown to be able to mediate specific liposomal drug delivery to CD40L+ cells. Loaded with the cytostatic drug methotrexate (MTX), the A25 modified liposome could significantly reduce the CD40L+ cell ratios in the experimental autoimmune encephalomyelitis (EAE) mice, resulting in great improvement in clinical scores. Since CD40L+ cells are involved in the pathological development of many auto-immune diseases, A25 conjugated drug targeting systems may be useful for developing therapies that are more efficacies and with less side effects.
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http://dx.doi.org/10.1016/j.jconrel.2015.03.035DOI Listing
June 2015

Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice.

Oncol Lett 2014 Oct 24;8(4):1638-1644. Epub 2014 Jul 24.

Department of Cardiothoracic Surgery, Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510120, P.R. China.

Drug resistance and immune deficiency are important factors for the poor prognosis of lung carcinoma. The present study explored the possible protective effect of immune reconstitution from peripheral blood mononuclear cells (PBMCs) on multi-drug-resistant human lung carcinoma Am1010 cells in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The inoculated tumor fragments grew rapidly in the NOD/SCID mice. The growth was significantly inhibited by intraperitoneal injection of PBMCs. In the mice injected with PBMCs, numerous CD3 and CD8 cells, but less CD4 cells, were found in spleen and tumor tissues. These data suggest that PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.
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http://dx.doi.org/10.3892/ol.2014.2379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156269PMC
October 2014

Effects of surface displayed targeting ligand GE11 on liposome distribution and extravasation in tumor.

Mol Pharm 2014 Oct 12;11(10):3242-50. Epub 2014 Sep 12.

School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, People's Republic of China.

Targeting ligands displayed on liposome surface had been used to mediate specific interactions and drug delivery to target cells. However, they also affect liposome distribution in vivo, as well as the tissue extravasation processes after IV injection. In this study, we incorporated an EGFR targeting peptide GE11 on liposome surfaces in addition to PEG at different densities and evaluated their targeting properties and antitumor effects. We found that the densities of surface ligand and PEG were critical to target cell binding in vitro as well as pharmacokinetic profiles in vivo. The inclusion of GE11-PEG-DSPE and PEG-DSPE at 2% and 4% mol ratios in the liposome formulation mediated a rapid accumulation of liposomes within 1 h after IV injection in the tumor tissues surrounding neovascular structures. This is in addition to the EPR effect that was most prominently described for surface PEG modified liposomes. Therefore, despite the fact that the distribution of liposomes into interior tumor tissues was still limited by diffusion, GE11 targeted doxorubicin loaded liposomes showed significantly better antitumor activity in tumor bearing mice as a result of the fast active-targeting efficiency. We anticipate these understandings can benefit further optimization of targeted drug delivery systems for improving efficacy in vivo.
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http://dx.doi.org/10.1021/mp5001718DOI Listing
October 2014

Polyspermine imine, a pH responsive polycationic siRNA carrier degradable to endogenous metabolites.

Mol Pharm 2014 Oct 2;11(10):3300-6. Epub 2014 Jun 2.

Shanghai Jiao Tong University School of Pharmacy , 800 Dongchuan Road, Shanghai 200240, China.

Cationic polymers readily degradable in response to cellular environment are especially favored as easy-formulating materials to pack siRNA into a nanoparticle and to release the cargo in the cytoplasm in time. In addition to the efficiency of cytosomal release, the degradation products should best be free of safety concerns, a typical challenge for cationic polymers. To satisfy the two criteria, we report a new cationic polymer, polyspermine imine, named as PSP-Imine, which is formed by condensing two endogenous molecules, spermine and glyoxal, through conjugated π linkage, -N═C-C═N- (Schiff base reaction), a poly linkage structure sufficiently stable under neutral condition but dissociative under the endosomal pH. Cellular assays under a confocal microscope indicated that the polyplex formed of PSP-Imine readily released the loaded siRNA to the cytoplasm after being engulfed in the target cells and efficiently silenced the target genes in different cell lines and xenograft mouse model of human cervical carcinoma, as compared with nondegradable PEI 25 kDa. Cell viability assays confirmed that PSP-Imine showed no visible cytotoxicity within the concentration being tested. The present study suggests that PSP-Imine is an excellent siRNA condensing material for forming the core of a therapeutically feasible synthetic carrier system.
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http://dx.doi.org/10.1021/mp500169pDOI Listing
October 2014

Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer.

Mol Cancer 2013 Dec 13;12:163. Epub 2013 Dec 13.

Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People's Republic of China.

Background: MicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.

Methods: The expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.

Results: We found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3' untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.

Conclusions: Our study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.
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http://dx.doi.org/10.1186/1476-4598-12-163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029407PMC
December 2013

Expression of gamma-aminobutyric acid receptors on neoplastic growth and prediction of prognosis in non-small cell lung cancer.

J Transl Med 2013 Apr 24;11:102. Epub 2013 Apr 24.

Guangdong Cardiovascular Institute, Southern Medical University, Guangzhou 510080 Guangdong Province, China.

Background: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the adult mammalian brain, but exerts physiologic effects other than that on neurotransmitter in non-neuronal peripheral tissues and organs. GABA may affect cancer growth through activation GABA receptors. We investigated the gene expression of GABA receptors in tissue of non-small cell lung cancers (NSCLC) and non-cancerous tissues, and found that the gene expression of GABA receptor phenotypes was correlated with tumorigenesis and clinical prognosis.

Methods: Sixty-one snap-frozen human samples of NSCLC tissues and paired non-cancerous tissues (5cm away from tumor) were analyzed. Gene expression of GABA receptors was detected by Real-time quantitative PCR (RT-qPCR). Survival times in relation to the expression of GABA receptor phenotypes were analyzed. Human NSCLC cell lines H1299, A549, H520, H460 and human bronchial epithelial cell line BEAS-2B were used to determine the phenotypes of GABA inhibitory effects on cancer cell growth. The effects of exogenous administration of GABA on H1299 cell growth were examined.

Results: The gene expressions were significantly higher in NSCLC tissues than in the paired non-cancerous tissues for GABAA receptor subunit α3 (GABR(A3), P = 0.030); for GABAA receptor subunit epsilon (GABRE, P = 0.036); and GABAB receptor subunit 2 (GABBR2, P = 0.005). Kaplan-Meier curves showed that patients with high expression of GABBR2 gene and low expression of GABR(A3 )gene had a better prognosis (P < 0.05). The administration of GABA resulted in suppressed proliferation of NSCLC cell lines in a dose- and time-dependent manner. The use of the GABA receptor antagonist CGP35348 could reverse the inhibitory effect.

Conclusions: The pattern of GABA receptor gene phenotype expression may be involved in the regulation of tumorigenesis. A high expression of GABBR2 with a low expression of GABR(A3) may predict a better outcome. The treatment with GABA attenuates cancer cell growth in vitro. The expression of GABA receptor may be not only promising genetic therapeutic targets but may also serve as valuable prognostic markers for NSCLC.
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http://dx.doi.org/10.1186/1479-5876-11-102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644491PMC
April 2013

[Expression of glypican-3 in lung squamous cell carcinoma and adenocarcinoma and its relation with prognosis].

Nan Fang Yi Ke Da Xue Xue Bao 2013 Feb;33(2):212-5

Department of Thoracic and Cardiovascular Surgery, Guangzhou Institute of Respiratory Disease, Guangzhou, China.

Objective: To study the different expressions of glypican-3 in lung squamous cell carcinoma and adenocarcinoma and explore the association of glypican-3 with the prognosis of the patients.

Methods: Glypican-3 expression was detected immunohistochemically in the tumor tissues and adjacent tissues from 48 cases of lung squamous cell carcinoma and adenocarcinoma. Kaplan-Meier method and log-rank test were used for survival analysis of the patients.

Results: Glypican-3 expression was detected in the tumor tissues in 29.2% (14/48) of the cases, but not in the adjacent tissues. Of the 22 patients with lung squamous cell carcinoma, 12 (54.5%) showed positive glypican-3 expression in the tumor tissue, a rate significantly higher than that in patients with lung adenocarcinoma [7.7% (2/26), P<0.01]. In all the glypican-3-positive cases, the tumor tissues showed stronger glypican-3 expression in cases with lymph node metastasis or poor tumor differentiation. Kaplan-Meier survival analysis did not indicate a significant correlation of glypican-3 expression with the prognosis of the lung cancer patients.

Conclusion: Patients with lung squamous cell carcinoma have higher glypican-3 expressions in the tumor tissues than those with lung adenocarcinoma, suggesting the value of glypican-3 protein as a potential marker to detect lung squamous cell carcinoma.
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February 2013

Recombinant high density lipoprotein nanoparticles for target-specific delivery of siRNA.

Pharm Res 2013 May 14;30(5):1203-14. Epub 2012 Dec 14.

School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.

Purpose: Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for treatments of numerous diseases. However, the progress towards broad application of siRNA requires the development of safe and effective vectors that target to specific cells. In this study, we developed a novel recombinant high density lipoprotein (rHDL) vector with high siRNA encapsulation efficiency.

Methods: They were prepared by condensing siRNA with various commercial cationic polymers and coating the polyplex with a layer of lipids and apolipoprotein AI (apo AI). The rHDL nanoparticles were used to transfect SMMC-7721 hepatoma cells with stable luciferase expression. The uptake and intracellular trafficing of siRNA were also investigated.

Results: Characterization studies revealed these rHDL nanoparticles had similar physical properties as natural HDLs. The various rHDL formulations had high silencing efficiency (more than 70% knockdown) in hepatocytes with minimum cytotoxicity. Moreover, the uptake of rHDL by SMMC-7721 was confirmed to be mediated through the natural HDL uptake pathway.

Conclusions: The work described here demonstrated the optimized rHDL nanoparticles may offer a promising tool for siRNA delivery to the liver.
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http://dx.doi.org/10.1007/s11095-012-0957-4DOI Listing
May 2013

Impact of PEGylation on biodistribution and tumor accumulation of Lipid-Mu peptide-DNA.

J Liposome Res 2013 Mar 19;23(1):1-10. Epub 2012 Oct 19.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

For gene-based therapeutic approaches that require transfection of specific cell targets in vivo, it is important to design the delivery system to have optimized tissue distribution. Surface PEGylation of liposomes and polymer nanoparticles has been shown to lead to prolonged blood circulation and also preferential accumulation in tumor sites resulting from the enhanced permeability and retention (EPR) effect. The aim of this study was to investigate the effect of different surface PEGylation densities on resulted biodistribution profiles of Lipid-Mu peptide-DNA (LMD) nanoparticles. LMD particles containing the near infrared fluorescent lipid dye, Cy5.5-DSPE, were injected intravenously, and whole-body fluorescence images of the live animal were recorded. Analysis of these time series of images indicated that LMDs with different surface PEG(2000) densities had distinctively different biodistribution and tumor accumulation profiles. LMDs containing approximately 15-25% of surface PEG(2000) were shown to have the highest accumulation and longest residence time in tumor. LMD distribution and pharmacokinetic profiles in other organs were also observed to be different and were analyzed.
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http://dx.doi.org/10.3109/08982104.2012.708934DOI Listing
March 2013

Establishment of an orthotopic lung cancer model in nude mice and its evaluation by spiral CT.

J Thorac Dis 2012 Apr;4(2):141-5

Objective: To establish a simple and highly efficient orthotopic animal model of lung cancer cell line A549 and evaluate the growth pattern of intrathoracic tumors by spiral CT.

Methods: A549 cells (5×10(6) mL(-1)) were suspended and inoculated into the right lung of BALB/c nude mice via intrathoracic injection. Nude mice were scanned three times each week by spiral CT after inoculation of lung cancer cell line A549. The survival time and body weight of nude mice as well as tumor invasion and metastasis were examined. Tissue was collected for subsequent histological assay after autopsia of mice.

Results: The tumor-forming rate of the orthotopic lung cancer model was 90%. The median survival time was 30.7 (range, 20-41) days. The incidence of tumor metastasis was 100%. The mean tumor diameter and the average CT value gradually increased in a time-dependent manner.

Conclusions: The method of establishing the orthotopic lung cancer model through transplanting A549 cells into the lung of nude mice is simple and highly successful. Spiral CT can be used to evaluate intrathoracic tumor growth in nude mice vividly and dynamically.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.03.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378238PMC
April 2012