Publications by authors named "Yehan Zhu"

17 Publications

  • Page 1 of 1

Long Noncoding RNA RP11-89K21.1 Interacts with miR-146a/b-5p to Promote Proliferation and Gefitinib Resistance Through Regulating RHPN2 and RhoA/ROCK Pathway in Lung Adenocarcinoma.

Cancer Biother Radiopharm 2021 Apr 20. Epub 2021 Apr 20.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.

Long noncoding RNAs (lncRNAs) have major roles in lung adenocarcinoma (LUAD). lncRNA RP11-89K21.1 was reported to be abnormally expressed in LUAD, yet its biological functions in LUAD progression remain unclear. The 40 LUAD tissues and pair-matched adjacent normal tissues were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to detect the expression of lncRNA, miRNA, and mRNA in LUAD samples and cell lines. Loss-of-function assays were used to evaluate the effects of RP11-89K21.1 on LUAD cell proliferation and gefitinib resistance. Bioinformatics analysis, luciferase reporter assay, and Western blot were employed to explore the regulatory relationships among RP11-89K21.1, miR-146a/b-5p, and RHPN2. The authors identified that RP11-89K21.1 was highly expressed in LUAD tissues and cell lines. Moreover, upregulated RP11-89K21.1 was strongly associated with unfavorable overall survival of patients with LUAD. Knockdown of RP11-89K21.1 significantly suppressed proliferation and sensitized cell to gefitinib. Mechanistically, RP11-89K21.1 could directly bind miR-146a-5p and miR-146b-5p and decrease their expression to upregulate RHPN2, and subsequently activated RhoA/ROCK pathway. More importantly, overexpression of RHPN2 reversed regulatory effects of RP11-89K21.1 knockdown on cell proliferation and gefitinib resistance. These observations provide new insights into the role of RP11-89K21.1 in regulating LUAD tumorigenesis, suggesting that RP11-89K21.1 is a potential therapeutic target for LUAD treatment.
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http://dx.doi.org/10.1089/cbr.2020.4395DOI Listing
April 2021

Expression of nuclear factor erythroid-2-related factor 2, broad complex-tramtrack-bric a brac and Cap'n'collar homology 1 and γ-glutamic acid cysteine synthase in peripheral blood of patients with chronic obstructive pulmonary disease and its clinical significance.

Exp Ther Med 2021 May 22;21(5):516. Epub 2021 Mar 22.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

The purpose of the present study was to explore the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2)/BTB-CNC allogeneic 1 (Bach1)/γ-glutamic acid cysteine synthase (γ-GCS) and chronic obstructive pulmonary disease (COPD). The expression of Nrf2, Bach1, γ-GCS mRNA and protein in the peripheral blood mononuclear cells (PBMCs) of 80 COPD patients and 40 healthy volunteers were studied. Then, the correlation between Nrf2, Bach1, γ-GCS and lung function, inflammation and oxidative stress indicators was analyzed. Compared with healthy controls, Nrf2, Bach1 mRNA and protein levels were significantly increased in the PBMCs of COPD patients, while γ-GCS mRNA and protein levels were significantly decreased. Nrf2 and Bach1 protein levels in the nucleus were significantly elevated in acute exacerbation COPD patients compared with patients with a stable stage of COPD, while γ-GCS mRNA levels were significantly reduced. In addition, it was found that Nrf2 nuclear protein levels were significantly reduced in COPD patients compared with the control group, while Bach1 nuclear protein levels were significantly increased. Correlation analysis in COPD group demonstrated that γ-GCS mRNA was positively correlated with Nrf2 nuclear protein level, but negatively correlated with Bach1 nuclear protein level. Further analysis demonstrated that γ-GCS mRNA and Nrf2 protein in the nucleus was positively correlated with forced expiratory volume in one second (FEV)/forced vital capacity (FVC)% and FEV% predicted, and Bach1 protein in the nucleus was negatively correlated with FEV/FVC% and FEV% predicted. Additionally, the expression levels of Nrf2, Bach1 and γ-GCS were also associated with smoking. The expression of Nrf2, Bach1 and γ-GCS in peripheral blood mononuclear cells of patients with COPD was dysregulated and related to lung function, which provides a new basis for exploring further the pathogenesis of COPD.
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http://dx.doi.org/10.3892/etm.2021.9947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014872PMC
May 2021

A Low Lean-to-Fat Ratio Reduces the Risk of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Patients with a Normal or Low Body Mass Index.

Med Sci Monit 2019 Jul 14;25:5229-5236. Epub 2019 Jul 14.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland).

BACKGROUND Increased risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) has been reported in patients who are overweight and obese. However, the effects of body fat in patients with normal or low body mass index (BMI) and COPD remain unknown. This study aimed to examine the association between acute exacerbations of COPD and the lean-to-fat (LTF) ratio in patients with a normal or low BMI. MATERIAL AND METHODS Patients with COPD (n=68) underwent assessment of body composition, in whom 43 cases had a normal BMI (18.5 to 25 kg/m²) and 14 cases were underweight (<18.5 kg/m²). Patients with COPD were treated according to current clinical guidelines and underwent regular follow-up for one year. Acute exacerbations of COPD were recorded. RESULTS BMI, the fat-free mass index (FFMI), skeletal muscle mass index (SMMI), and LTF ratio had no significant effect of the risk of acute exacerbations of COPD in the whole study cohort, but a low LTF ratio was significantly associated with reduced risk of acute exacerbations of COPD in the subgroup with a BMI<25 kg/m² (OR=4.528; P<0.05). The Fat Mass Index (FMI) had a protective effect in the whole cohort (OR=0.292; P=0.024) and in the subgroup with BMI <25 kg/m² (OR=0.253, P=0.049). The cumulative incidence of acute exacerbations of COPD was significantly increased in the patients with a high LTF ratio in the whole cohort (P=0.047) and in the subgroup with BMI <25 kg/m² (P=0.014). CONCLUSIONS In patients with BMI <25 kg/m², the LTF ratio was positively correlated with the risk of occurrence of acute exacerbations of COPD.
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http://dx.doi.org/10.12659/MSM.914783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647929PMC
July 2019

The fifth influenza A(H7N9) epidemic: A family cluster of infection in Suzhou city of China, 2016.

Int J Infect Dis 2018 Sep 5;74:128-135. Epub 2018 May 5.

Suzhou Center for Disease Control and Prevention, Suzhou, Jiangsu Province, China. Electronic address:

Objective: Influenza A(H7N9) virus is known for its high pathogenicity in human. A family cluster of influenza A(H7N9) virus infection was identified in Suzhou, China. This study aimed to investigate the possibility of human-to-human transmission of the virus and examine the virologic features of this family cluster.

Methods: The clinical and epidemiologic data of two patients in the family cluster of influenza A(H7N9) virus infection were collected. Viral RNA in samples derived from the two patients, their close contacts, and the environments with likely influenza A(H7N9) virus transmission were tested by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay. Hemagglutination inhibition (HI) assay was used to detect virus-specific antibodies. Genetic sequencing and phylogenetic analysis were also performed.

Results: The index patient (Case 1), a 66-year old man, was virologically diagnosed with influenza A(H7N9) virus infection 12days after experiencing influenza-like symptoms, then died of multi-organ failure. His 39-year old daughter (Case 2), denying any other exposure to influenza A(H7N9) virus, became infected with influenza A(H7N9) virus following taking care of her father during his illness. Sequencing viral genomes isolated from the two patients showed nearly identical nucleotide sequence, and genetically resembled the viral genome isolated from a chicken in the wet market where the index patient once visited. All three influenza A(H7N9) viruses shared S138A, G186V, Q226L mutations in HA (H3) protein and a single basic amino acid (PEIPKGR↓G) at the cleavage site.

Conclusions: Human-to-human transmission of influenza A(H7N9) virus most likely occurred in this household. The three-amino-acid mutations in HA protein were discovered in this study, which might have increased the binding affinity of influenza A(H7N9) virus to the receptor on trachea epithelial cells to facilitate viral transmission among humans.
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http://dx.doi.org/10.1016/j.ijid.2018.04.4322DOI Listing
September 2018

H19 promotes non-small-cell lung cancer (NSCLC) development through STAT3 signaling via sponging miR-17.

J Cell Physiol 2018 10 25;233(10):6768-6776. Epub 2018 Apr 25.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

LncRNAs can exhibit crucial roles in the development of multiple cancers, including non-small cell lung cancer (NSCLC). Currently, we investigated the role of lncRNA H19 in NSCLC. In our study, it was found that H19 was upregulated in A549 and H1299 cells compared to normal lung epithelial BEAS-2B cells. Meanwhile, we observed that miR-17 was downregulated in NSCLC cell lines. Inhibited H19 can suppress the growth, migration, and invasion of NSCLC cells and bioinformatics search was performed to predict the correlation between H19 and miR-17. Overexpression of miR-17 was able to inhibit the progression of NSCLC cells while reversely miR-17 inhibitors reversed this process. In addition, signal transducers and activators of transcription (STAT3), as an mRNA target of miR-17, was presented in our research. Moreover, we discovered that H19 demonstrated its biological functions via regulating miR-17 and STAT3 in vitro. Silencing H19 greatly increased STAT3 expression by sponging miR-19 in vitro. It was hypothesized that H19 may serve as a competing endogenous RNA (ceRNA) to modulate STAT3 by attaching miR-17 in lung cancer. In summary, our findings indicated that H19/miR-17/STAT3 axis participated in NSCLC development. H19 could be regarded as a significant prognostic biomarker in NSCLC progression.
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http://dx.doi.org/10.1002/jcp.26530DOI Listing
October 2018

Crucial role of OX40/OX40L signaling in a murine model of asthma.

Mol Med Rep 2018 Mar 18;17(3):4213-4220. Epub 2018 Jan 18.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L) signaling and OX40+ T cells in ovalbumin (OVA)‑induced mouse asthma model. Asthma was induced by OVA exposure and subsequent co‑treatment with OX40L protein, neutralizing anti‑OX40L blocking antibody, OX40+ T cells or PBS. The protein expression levels of interleukin (IL)‑4, IL‑6, IL‑13, IL‑17, tumor necrosis factor (TNF)‑α and interferon (IFN)‑γ in bronchoalveolar lavage fluid (BALF) were examined using murine cytokine‑specific ELISA. Eosinophil accumulation as well as proliferation and apoptosis of T cells in BALF were detected by Cell Counting kit‑8 and flow cytometric assays. Expression of the apoptosis‑related protein cleaved caspase‑3 was examined in OX40+ T cells using western blot assay. Flow cytometric analysis revealed that OVA‑treated mice that were co‑treated with OX40L or OX40+ T cells exhibited higher eosinophil infiltration compared with control mice treated only with OVA, whereas neutralizing anti‑OX40L blocking antibody inhibited eosinophil infiltration. ELISA assays demonstrated that the expression of IL‑4, IL‑6, IL‑13, IL‑17, TNF‑α and IFN‑γ in BALF in OX40L‑treated and OX40+ T cell‑treated mice was increased compared with expression levels in control mice. Treatment with OX40L protein effectively reduced apoptosis of T cells and the expression of cleaved caspase‑3 in T cells. OX40L‑treated and OX40+ T cell‑treated mice exhibited increased asthma through OX40/OX40L signaling, which probably promoted inflammatory factor expression, eosinophil infiltration and T cell proliferation.
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http://dx.doi.org/10.3892/mmr.2018.8453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802192PMC
March 2018

[Report of Successful Treatment of A Rectal Cancer Patient with Endobronchial 
Metastasis by Bronchial Stent Implantation Combined with Chemotherapy and Apatinib].

Zhongguo Fei Ai Za Zhi 2017 Sep;20(9):657-660

Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.

The lungs are the most common sites of metastases from non-pulmonary malignancies. On the other hand, endobronchial metastases are rare. Various tumors have been associated with endobronchial metastasis, most commonly renal, breast and colorectal cancer. Advanced rectal cancerwith lung metastasis is common. However, endobronchial metastasis without lung metastasis of rectal cancer is rare, and easily misdiagnosed. We report one case of postoperative rectal cancer with endobronchial, pleuralcavity, pericardial cavitymetastasis, giving the comprehensive treatment of bronchial stentimplantation, chemotherapy, targeted drugs and remission. The process of diagnosis and treatmentis relatively complex, therefore it has a certain clinical reference value.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2017.09.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973369PMC
September 2017

Measuring Endotracheal Tube Depth by Bedside Ultrasound in Adult Patients in an Intensive Care Unit: A Pilot Study.

Ultrasound Med Biol 2017 06 17;43(6):1163-1170. Epub 2017 Mar 17.

Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address:

The aim of the study described here was to evaluate the feasibility and accuracy of measuring endotracheal tube (ETT) depth with ultrasound in adult patients in an intensive care unit (ICU). The distance between the upper margin of the cuff and the upper margin of the aortic arch (Duc-ua) of 67 ICU patients was measured by ultrasound, and the time of measurement was recorded. The level of agreement between the distance between the tip of the ETT and the carina (Dtt-c) measured by ultrasound (U-Dtt-c) and Dtt-c measured by bronchoscopy (B-Dtt-c) was assessed using linear regression and a Bland-Altman plot. There was a significant correlation between B-Dtt-c and U-Dtt-c (r = 0.844, p < 0.001). Also, the Bland-Altman plot revealed strong agreement between B-Dtt-c and U-Dtt-c. The time it took to measure ETT depth by ultrasound was 33.91 ± 5.43 s. In conclusion, bedside ultrasound provides a novel and convenient method for measuring the depth of ETT in ICU patients.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.01.018DOI Listing
June 2017

Sudden Cardiac Arrest Triggered by Coadministration of Fluconazole and Amiodarone.

Cardiology 2017;137(2):92-95. Epub 2017 Feb 9.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.

Fluconazole for fungal infections and amiodarone for arrhythmia are commonly prescribed medications, and coadministration of such medications is sometimes inevitable in clinical practice. However, both medications have been associated with prolonged QTc intervals and subsequent arrhythmias, which are sometimes fatal. We present the case of a 75-year-old man with sudden cardiac arrest triggered by coadministration of fluconazole and amiodarone, which raises the need for caution regarding coadministration of these medications. To our knowledge, this case has not been previously described.
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http://dx.doi.org/10.1159/000455825DOI Listing
August 2018

Enhanced suppression of polyclonal CD825 regulatory T cells via exosomal arming of antigen-specific peptide/MHC complexes.

J Leukoc Biol 2017 05 17;101(5):1221-1231. Epub 2017 Jan 17.

Cancer Research Department, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Compared with CD425 regulatory T cells (T), the mechanisms for natural, polyclonal CD825 T immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD825 T or CD825 T armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DC)-stimulated antitumor immunity. We demonstrate that CD825 T inhibit T cell proliferation in vitro in a cell contact-dependent fashion but independent of the expression of immunosuppressive IL-10, TGF-β, and CTLA-4. CD825 T anergize naïve T cells upon stimulation by up-regulating T cell anergy-associated and down-regulating IL-2 production. T also anergize DCs by preventing DC maturation through the down-regulation of Ia, CD80, CD86, and inflammatory cytokines, leading to defects in T cell stimulation. Moreover, CD825 T inhibit CTLs through inducing CTL death via perforin-mediated apoptosis and through reducing effector CTL cytotoxic activity via down-regulating CTL perforin-production and degranulation. In addition, we show that CD825 T suppress DC-stimulated CTL responses in priming and effector phases and inhibit immunity against OVA-expressing CCL lung cancer. Remarkably, polyclonal CD825 T armed with OVA-specific exosomal pMHC class-II (pMHC-II), or pMHC class-I (pMHC-I) complexes exert their enhanced inhibition of CTL responses in the priming and the effector phases, respectively. Taken together, our investigation reveals that assigning antigen specificity to nonspecific polyclonal CD825 T for enhanced immune suppression can be achieved through exosomal pMHC arming. This principle may have a great effect on T-mediated immunotherapy of autoimmune diseases.
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http://dx.doi.org/10.1189/jlb.3A0716-295RRDOI Listing
May 2017

Rapid and partial remission of primary lesion but complicated by secondary fibrosis after treatment with nivolumab in a lung squamous carcinoma.

Ther Adv Respir Dis 2017 02 30;11(2):129-132. Epub 2016 Nov 30.

Respiratory Department, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China.

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http://dx.doi.org/10.1177/1753465816680574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933639PMC
February 2017

Primary pulmonary T-cell lymphoma mimicking pneumonia: A case report and literature review.

Exp Ther Med 2016 Jul 21;12(1):365-368. Epub 2016 Apr 21.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Primary pulmonary T-cell lymphoma is an extremely rare neoplasm. The present study describes the case of an elderly male patient who was admitted to hospital with initial symptoms including a fever, coughing and dyspnea. A chest computed tomography scan detected pneumonia-like features, including multiple variable nodules, ground-glass opacities, patchy infiltration and subpleural consolidation, which progressed rapidly. No mediastinal or hilar adenopathy was noted. The patient was initially diagnosed with severe pneumonia; however, the patient developed severe respiratory failure and extensive progression in radiographic manifestation despite receiving a combination treatment of broad-spectrum antibiotics and antifungal agents. Negative results were obtained for anti-nuclear antibodies and anti-neutrophil cytoplasmic antibody assays, which eliminated the possibility that the patient was affected by a connective tissue disease. A bronchoscopy with transbronchial lung biopsy was not performed on account of intolerance. A histological examination, which was performed using specimens obtained via video-assisted thoracoscopic surgery, allowed the final diagnosis of T-cell lymphoma to be confirmed. Unfortunately, the patient succumbed to respiratory failure and a probable thoracic hemorrhage prior to the initiation of chemotherapy.
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http://dx.doi.org/10.3892/etm.2016.3287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906885PMC
July 2016

[Diagnostic value of computed tomography-guided percutaneous needle biopsy versus radial probe endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions].

Zhonghua Jie He He Hu Xi Za Zhi 2015 Dec;38(12):897-900

Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215006, China; Email:

Objective: To evaluate the value of computed tomography-guided percutaneous needle biopsy (CT-PNB) and radial probe endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in the diagnosis of peripheral pulmonary lesions(PPLs).

Methods: The clinical data of 213 patients who were diagnosed as to have PPLs in the First Affiliated Hospital of Soochow University between December 1, 2012 and October 1, 2014 were studied retrospectively. The patients were divided into CT-PNB group and EBUS-TBLB group, according to biopsy methods. The diagnostic yield, complications and influencing factors of both groups were evaluated.

Results: The diagnostic yield (87.2%, 102/117) and complication rate (18.8%, 22/117) of the CT-PNB group were higher than those of the EBUS-TBLB group(61.5%, 59/96 and 18.8%, 22/117, respectively), the differences being statistically significant (χ(2)=18.906, P=0.000 and χ(2)=10.542, P=0.001, respectively). Analysis of the influencing factors showed that there were statistically significant correlations between pneumothorax and the lesion diameter(χ(2)=5.785, P=0.016) and location(χ(2)=7.559, P=0.006) in the CT-PNB group. The diagnostic yield was correlated with lesion diameter(χ(2)=7.995, P=0.004) and location(χ(2)=4.608, P=0.027) in the EBUS-TBLB group. There was no complicated pneumothorax if the lesions were attached to the chest wall in the CT-PNB group.

Conclusions: The diagnostic yield of CT-PNB in PPLs was better than that of EBUS-TBLB. Although CT-PNB had a higher complication rates, most complications were mild.
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December 2015

Innate and adoptive immune cells contribute to natural resistance to systemic metastasis of B16 melanoma.

Cancer Biother Radiopharm 2015 Mar 25;30(2):72-8. Epub 2015 Feb 25.

1 Cancer Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan , Saskatoon, Canada .

The greatest hurdle in cancer treatment is the metastasis of primary tumors to distant organs. Our knowledge on how different immune cells, in the absence of exogenous stimulation, prevent tumor metastasis in distant organs is poorly understood. Using a highly metastatic murine lung B16 melanoma cell line BL6-10, we employed naive mice that genetically lack CD4(+) or CD8(+) T cells, or are depleted of dendritic cells (DCs) or natural killer (NK) cells to understand the relative importance of these cells in metastasis prevention. Irrespective of the presence of naïve CD4(+) T, CD8(+) T, DCs, or NK cells, lungs, which act as primary site of predilection for B16 melanoma, readily developed numerous lung BL6-10 melanoma colonies. However, their absence led to B16 melanoma metastasis in variable proportions to distant organs, particularly livers, kidneys, adrenals, ovaries, and hearts. NK cells mediate prevention of BL6-10 metastasis to various organs, especially to livers. Mechanistically, CD40L signaling, a critical factor required for DC licensing and CD8(+) cytotoxic T lymphocyte (CTL) responses, was required for CD4(+) T cell-mediated prevention of systemic BL6-10 metastasis. These results suggest that the composition and functions of different immune cells in distant tissue microenvironments (distant organs other than primary sites of predilection) robustly mediate natural resistance against melanoma metastasis. Thus, harnessing these immune cells' responses in immunotherapeutics would considerably limit organ metastasis.
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http://dx.doi.org/10.1089/cbr.2014.1736DOI Listing
March 2015

[Effect of adenovirus-mediated ING4 and IL-24 co-expression on chemosensitivity to human lung adenocarcinoma in vitro and in vivo].

Sheng Wu Gong Cheng Xue Bao 2011 Jan;27(1):85-94

Department of Respiratory, First Affiliated Hospital in Soochow University, Suzhou 215006, China.

To study the chemosensitivity and the mechanisms of recombinant adenovirus vector expressing ING4 and IL-24 (Ad-ING4-IL-24) on lung adenocarcinoma in vitro and in vivo, the expression of ING4 and IL-24 in A549 cells was detected by RT-PCR and Western blotting. The growth inhibition, apoptosis rate and apoptosis body were measured by MTT, flow cytometry and Hoechst staining respectively. For in vivo study, we first established the A549 tumor model by grafting A549 cells in athymic nude mice; and then injected Ad-ING4-IL-24 into the tumors. Two weeks after injection, we killed the mice, removed the tumors, weighted and calculated the ratios of tumor-suppression. We also detected the expressions of ING4, IL-24, bax, bcl-2, VEGF with immunohistochemistry. The results indicated that ING4 and IL-24 were proved successfully transcription and expression in A549 cells. More interestingly, the joint group inhibited the growth of A549 cells and induced apoptosis. The in vivo data showed that the joint group suppressed the tumor growth conspicuously through up-regulating the expression of bax, and down-regulating the expression of bcl-2, VEGF. The study proved that Ad-ING4-IL-24 significantly enhanced the chemosensitivity to anticancer drug DDP in lung adenocarcinoma, which may related with cell apoptosis and antiangiogenesis.
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January 2011

Genetic variants in interleukin-6 modified risk of obstructive sleep apnea syndrome.

Int J Mol Med 2009 Apr;23(4):485-93

Department of Respiratory Medicine, The First Affiliated Hospital, Medical College of Soochow University, Suzhou, PR China.

Obesity and inflammation are known to correlate with the pathogenesis of obstructive sleep apnea syndrome (OSAS). Interleukin (IL)-6, an important regulator of obesity and inflammation, was reported to phenotypically increase in patients with OSAS. This study aimed to investigate whether genetic variants in IL-6 confer susceptibility to OSAS. The study population consisted of 151 patients with OSAS and 75 healthy controls from Southeast China. Five haplotype-tagging single nucleotide polymorphisms (tSNPs) were selected across 21 kb of the IL-6 locus using Haploview software V4.1. The tSNPs were amplified by polymerase chain reaction (PCR) and genotyped by restriction enzyme digestion followed by gel electrophoresis. Linkage disequilibrium (LD) and haplotype reconstruction were carried out by means of a SHEsis program. No distribution difference of any of the five tSNPs between OSAS patients and controls was observed. However, in non-obese individuals (n=117), the minor allele G (rs1800796) decreased risk of OSAS compared with the major allele C [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.26-0.86; p=0.014], and the haplotype TG (rs1880242, rs1800796) conferred a significantly decreased risk of OSAS than single allele G (rs1800796) (OR, 0.39; 95% CI, 0.20-0.74; p=0.003). Moreover, the severity of sleep-disordered breathing (measured by apnea hypopnea index) increased linearly in carriers of the C variant of IL-6 -572G/C polymorphism (14.3+/-5.1, 22.0+/-3.6 and 34.8+/-3.5 for GG, CG and CC, respectively; p=0.012). To the best of our knowledge, this is the first study to suggest that genetic variants in IL-6 could modify OSAS susceptibility. SNP genotyping of IL-6 is a potential strategy for detecting the risk of breathing disordered diseases in non-obese individuals.
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http://dx.doi.org/10.3892/ijmm_00000155DOI Listing
April 2009

Recombinant human IL-24 suppresses lung carcinoma cell growth via induction of cell apoptosis and inhibition of tumor angiogenesis.

Cancer Biother Radiopharm 2008 Jun;23(3):310-20

Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, China.

Previous studies have shown that interleukin-24 (IL-24; mda-7) as a novel tumor suppressor gene has tumor-suppressive activity against a broad spectrum of human cancers. However, the therapeutic effect of the recombinant human IL-24 (rhIL-24) protein purified from prokaryotic cells on human lung cancers has not been reported. In this study, we cloned the human gene coding for IL-24 from lipopolysaccharide-activated human peripheral blood mononuclear cells (PBMCs) by reverse-transcriptase polymerase chain reaction and constructed an expression vector pBV220-IL-24. We then transfected Escherichia coli DH5alpha with pBV220-IL-24. The soluble rhIL-24 was obtained from purified insoluble inclusion bodies of transfected cells by a denaturing and renaturing process. We demonstrated that the purified soluble rhIL-24 protein with 18.5 kappaDa was capable of (1) inducing in vitro apoptosis of A549 lung carcinoma cells; (2) activating PBMCs to secrete cytokines such as IL-6, tumor necrosis factor-alpha, and interferon-gamma; (3) inhibiting the formation of blood capillaries on chicken embryonic allantois and in vivo tumor angiogenesis; and (4) inhibiting A549 lung tumor cell growth in vitro and in vivo. Therefore, our results indicate its potent suppressive effect on human lung carcinoma cell line and warrant its further investigation for therapeutic application against human lung cancer.
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http://dx.doi.org/10.1089/cbr.2007.0453DOI Listing
June 2008