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[PMID]: 26980915
[Au] Autor:Rosko AJ; Birkeland AC; Wilson KF; Muenz DG; Bellile E; Bradford CR; McHugh JB; Spector ME
[Ad] Address:Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA....
[Ti] Title:Tumor Biomarkers in Spindle Cell Variant Squamous Cell Carcinoma of the Head and Neck.
[So] Source:Otolaryngol Head Neck Surg;155(1):106-12, 2016 Jul.
[Is] ISSN:1097-6817
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To determine biomarkers of recurrence and survival in patients with spindle cell variant squamous cell carcinoma (SpSCC) of the head and neck. STUDY DESIGN: Retrospective case control study. SETTING: Tertiary academic center. SUBJECTS AND METHODS: Thirty-two SpSCC patients (mean age, 68.8) between 1987 and 2009 were identified and reviewed. A tissue microarray (TMA) was constructed from tumor specimens. Tumor biomarkers under study included p16, epidermal growth factor receptor (EGFR), p53, EZH2, cyclin D1, CD104, HGFa, p21, and cMET. An additional TMA was constructed from patients with non-SpSCC oral cavity squamous cell carcinoma for comparative purposes. The main outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). RESULTS: In the SpSCC cohort, tumors positive for cMet had worse OS (P < .001). Patients positive for cMet (P = .007), cyclin D1 (P = .019), and p16 (P = .004) had worse DSS. Recurrence-free survival was also worse in patients with tumors positive for cMet (P = .037), cyclin D1 (P = .012), and p16 (P < .001). Compared with the oral cavity cohort, there was a significantly larger proportion of patients in the SpSCC group with tumors staining positive for cMet and a lower proportion of tumors positive for cyclin D1. CONCLUSION: cMet, cyclin D1, and p16 are predictive tumor biomarkers for risk of recurrence and worse DSS in patients with SpSCC.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Cu] Class update date: 160702
[Lr] Last revision date:160702
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1177/0194599816636612

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[PMID]: 27197149
[Au] Autor:Morris ZS; Guy EI; Francis DM; Gressett MM; Werner LR; Carmichael LL; Yang RK; Armstrong EA; Huang S; Navid F; Gillies SD; Korman A; Hank JA; Rakhmilevich AL; Harari PM; Sondel PM
[Ad] Address:Department of Human Oncology, University of Wisconsin, Madison, Wisconsin. zmorris@uwhealth.org....
[Ti] Title:In Situ Tumor Vaccination by Combining Local Radiation and Tumor-Specific Antibody or Immunocytokine Treatments.
[So] Source:Cancer Res;76(13):3929-41, 2016 Jul 1.
[Is] ISSN:1538-7445
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Interest in combining radiotherapy and immune checkpoint therapy is growing rapidly. In this study, we explored a novel combination of this type to augment antitumor immune responses in preclinical murine models of melanoma, neuroblastoma, and head and neck squamous cell carcinoma. Cooperative effects were observed with local radiotherapy and intratumoral injection of tumor-specific antibodies, arising in part from enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We could improve this response by combining radiation with intratumoral injection of an IL2-linked tumor-specific antibody (termed here an immunocytokine), resulting in complete regression of established tumors in most animals associated with a tumor-specific memory T-cell response. Given the T-cell response elicited by combined local radiation and intratumoral immunocytokine, we tested the potential benefit of adding this treatment to immune checkpoint blockade. In mice bearing large primary tumors or disseminated metastases, the triple-combination of intratumoral immunocytokine, radiation, and systemic anti-CTLA-4 improved primary tumor response and animal survival compared with combinations of any two of these three interventions. Taken together, our results show how combining radiation and intratumoral immunocytokine in murine tumor models can eradicate large tumors and metastases, eliciting an in situ vaccination effect that can be leveraged further by T-cell checkpoint blockade, with immediate implications for clinical evaluation. Cancer Res; 76(13); 3929-41. ©2016 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Cu] Class update date: 160702
[Lr] Last revision date:160702
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/0008-5472.CAN-15-2644

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[PMID]: 27339168
[Au] Autor:Bauman JE; Zang Y; Sen M; Li C; Wang L; Egner PA; Fahey JW; Normolle DP; Grandis JR; Kensler TW; Johnson DE
[Ad] Address:Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania....
[Ti] Title:Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane.
[So] Source:Cancer Prev Res (Phila);9(7):547-57, 2016 Jul.
[Is] ISSN:1940-6215
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Cu] Class update date: 160702
[Lr] Last revision date:160702
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1940-6207.CAPR-15-0290

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[PMID]: 27150634
[Au] Autor:Lubet RA; Townsend R; Clapper ML; Juliana MM; Steele VE; McCormick DL; Grubbs CJ
[Ad] Address:Division of Cancer Prevention, Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, Maryland....
[Ti] Title:5MeCDDO Blocks Metabolic Activation but not Progression of Breast, Intestine, and Tongue Cancers. Is Antioxidant Response Element a Prevention Target?
[So] Source:Cancer Prev Res (Phila);9(7):616-23, 2016 Jul.
[Is] ISSN:1940-6215
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.7 ppm) decreased tumor multiplicity by 90%, 80%, and 50%, respectively. This anti-initiating effect which is presumably mediated by altered metabolic activation parallels our observation that 5MeCDDO induced proteins of various antioxidant response element (ARE)-related phase II drug-metabolizing enzymes [e.g., GST Pi, AKR 7A3 (aflatoxicol), epoxide hydrolase, and quinone reductase] in the liver. 5MeCDDO tested in the 4-nitroquinoline-l-oxide (4-NQO) head and neck cancer model failed to decrease tumor incidence or invasiveness. In the Min mouse model of intestinal cancer, a high dose of 5MeCDDO (80 ppm) was weakly effective in reducing adenoma multiplicity [∼30% (P < 0.05)]; however, a lower dose was totally ineffective. These findings question whether measuring increased levels of certain ARE-related genes (e.g., quinone reductase, GST Pi), indicating decreased carcinogen activation are sufficient to imply general chemopreventive efficacy of a given agent or mixture. Cancer Prev Res; 9(7); 616-23. ©2016 AACR.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1607
[Cu] Class update date: 160702
[Lr] Last revision date:160702
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1158/1940-6207.CAPR-15-0294

  5 / 369347 MEDLINE  
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[PMID]: 26937925
[Au] Autor:Shen CH; Chou CH; Liu FC; Lin TY; Huang WY; Wang YC; Kao CH
[Ad] Address:From the Division of Pulmonary and Critical Care Medicine (C-HS), Department of Internal Medicine; Department of Neurology (C-HC); Division of Rheumatology/Immunology and Allergy (F-CL); Division of Infectious Diseases and Tropical Medicine (T-YL), Department of Internal Medicine; Department of Radiation Oncology (W-YH), Tri-Service General Hospital, National Defense Medical Center, Taipei; School of Medicine (Y-CW), China Medical University; Management Office for Health Data (Y-CW), China Medical University Hospital; Graduate Institute of Clinical Medical Science (C-HK), College of Medicine, China Medical University, Taichung; and Department of Nuclear Medicine and PET Center (C-HK), China Medical University Hospital, Taichung, Taiwan.
[Ti] Title:Association Between Tuberculosis and Parkinson Disease: A Nationwide, Population-Based Cohort Study.
[So] Source:Medicine (Baltimore);95(8):e2883, 2016 Feb.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Few studies have investigated the association between tuberculosis (TB) and Parkinson disease (PD). This nationwide, population-based, retrospective cohort study investigated the risk of PD in patients with TB.We selected patients newly diagnosed with TB (International Classification of Diseases, Ninth Revision, Clinical Modification: 011) from 2000 to 2009 in the Taiwan National Health Insurance Database as the TB cohort. The comparison cohort (the non-TB cohort) was frequency matched to the TB cohort at a ratio of 4:1 by sex, age, and the index date. We analyzed the risks of PD by using Cox proportional hazard regression models.A total of 121,951 patients with TB and 487,800 non-TB controls were enrolled in this study. The TB cohort had a 1.38-fold risk of PD compared with the non-TB cohort after adjustment for age, sex, and comorbidities (aHR, 95% CI: 1.30-1.46). The adjusted risk of PD in the TB and non-TB cohorts increased in subgroups regardless of age, sex, and comorbidities. Combined effect of TB and comorbidities on the risk of PD were significant in patients with TB who had diabetes (aHR: 2.26, 95% CI: 2.02-2.52), hypertension (aHR: 2.23, 95% CI: 2.04-2.44), head injury (aHR: 2.32, 95% CI: 1.95-2.77), chronic kidney disease (aHR: 2.02, 95% CI: 1.49-2.72), chronic obstructive pulmonary disease (aHR: 1.84, 95% CI: 1.66-2.05), depression (aHR: 4.66, 95% CI: 3.59-6.05), dementia (aHR: 3.70, 95% CI: 2.99-4.59), and stroke (aHR: 2.56, 95% CI: 2.28-2.87). The risk of PD was higher in a follow-up within 1 year (aHR: 1.78, 95% CI: 1.58-2.00) and decreased with the follow-up period in the TB cohort.Patients with TB have an independently 1.38-fold risk of PD. The risk of PD decreased with the follow-up period in the TB cohort. Physicians should be aware of the risk of PD in patients with TB when treating such patients.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Cu] Class update date: 160325
[Lr] Last revision date:160325
[Js] Journal subset:AIM; IM
[St] Status:In-Process
[do] DOI:10.1097/MD.0000000000002883

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[PMID]: 26937921
[Au] Autor:Fromonot J; Chaumet G; Gavarry O; Rostain JC; Lucciano M; Joulia F; Brignole M; Deharo JC; Guieu R; Boussuges A
[Ad] Address:From the UMR-MD2, Dysoxie Suractivité, Institut de Recherche Biomédicale des Armées (IRBA) & Aix-Marseille Université, Faculté de Médecine Nord, Marseille, France (JF, GC, J-CR, FJ, J-CD, RG, AB); Laboratoire HandiBio EA 4322, Université du Sud Toulon Var, La Garde, France (OG); Laboratoire de biomécanique appliquée, Aix Marseille Université, Faculté de Médecine Nord, Marseille, France (ML); and Department of Cardiology, Arrhythmologic Centre, Ospedali del Tigullio, Lavagna, Italy (MB).
[Ti] Title:Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers: A Randomized Study.
[So] Source:Medicine (Baltimore);95(8):e2876, 2016 Feb.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing.Seventeen healthy male volunteers (mean age 35 ±â€Š11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels.No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ±â€Š0.08 µM) and during head-up tilt test (0.33 ±â€Š0.09 µM) when compared with baseline (0.6 ±â€Š0.1 µM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ±â€Š0.1 µM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air.These results suggest that hyperoxia was able to increase blood pressure during head-up tilt test via a decrease in plasma adenosine concentration. Our results also suggest that adenosine receptor antagonists are worth trying in neurocardiogenic syncope.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Cu] Class update date: 160325
[Lr] Last revision date:160325
[Js] Journal subset:AIM; IM
[St] Status:In-Process
[do] DOI:10.1097/MD.0000000000002876

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[PMID]: 26937914
[Au] Autor:Abdalbary SA; Elshaarawy EA; Khalid BE
[Ad] Address:From the Department of Physical Therapy for Musculoskeletal Disorder and its Surgery (SAA), Faculty of Physical Therapy, October 6 University, Cairo; and Department of Anatomy and Embryology (EAAE, BEAK), Faculty of Medicine, Cairo University, Egypt.
[Ti] Title:Tensile Properties of the Deep Transverse Metatarsal Ligament in Hallux Valgus: A CONSORT-Compliant Article.
[So] Source:Medicine (Baltimore);95(8):e2843, 2016 Feb.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The deep transverse metatarsal ligament (DTML) connects the neighboring2 metatarsal heads and is one of the stabilizers connecting the lateral sesamoid and second metatarsal head. In this study, we aimed to determine the tensile properties of the DTML in normal specimens and to compare these results with hallux valgus specimens. We hypothesized that the tensile properties of the DTML would be different between the 2 groups of specimens.The DTML in the first interspace was dissected from 12 fresh frozen human cadaveric specimens. Six cadavers had bilateral hallux valgus and the other 6 cadavers had normal feet. The initial length (L0) and cross-sectional area (A0) of the DTML were measured using a digital caliper, and tensile tests with load failure were performed using a material testing machine.There were significant between-groups differences in the initial length (L0) P = 0.009 and cross-sectional area (A0) of the DTML P = 0.007. There were also significant between-groups differences for maximum force (N) P = 0.004, maximum distance (mm) P = 0.005, maximum stress (N/mm) P = 0.003, and maximum strain (%) P = 0.006.The DTML is an anatomical structure for which the tensile properties differ in hallux valgus.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1603
[Cu] Class update date: 160325
[Lr] Last revision date:160325
[Js] Journal subset:AIM; IM
[St] Status:In-Process
[do] DOI:10.1097/MD.0000000000002843

  8 / 369347 MEDLINE  
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[PMID]: 26908107
[Au] Autor:Melmed S
[Ad] Address:Cedars-Sinai Medical Center, Los Angeles, California 90048.
[Ti] Title:Pituitary Medicine From Discovery to Patient-Focused Outcomes.
[So] Source:J Clin Endocrinol Metab;101(3):769-77, 2016 Mar.
[Is] ISSN:1945-7197
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:CONTEXT: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. OBJECTIVE: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. DESIGN: Author's perspective on reports of pituitary advances in the published literature. SETTING: Clinical and translational Endocrinology. OUTCOMES: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. CONCLUSIONS: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Em] Entry month:1603
[Cu] Class update date: 160403
[Lr] Last revision date:160403
[Js] Journal subset:AIM; IM
[St] Status:In-Process
[do] DOI:10.1210/jc.2015-3653

  9 / 369347 MEDLINE  
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[PMID]: 26876356
[Au] Autor:Giri SS; Sen SS; Jun JW; Park SC; Sukumaran V
[Ad] Address:Laboratory of Aquatic Biomedicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151742, South Korea; Dept. of Biotechnology, Periyar Maniammai University, Thanjavur 613403, Tamil Nadu, India. Electronic address: giribiotek@gmail.com....
[Ti] Title:Heat-killed whole-cell products of the probiotic Pseudomonas aeruginosa VSG2 strain affect in vitro cytokine expression in head kidney macrophages of Labeo rohita.
[So] Source:Fish Shellfish Immunol;50:310-6, 2016 Mar.
[Is] ISSN:1095-9947
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Present study was undertaken to investigate the efficiency of heat-killed whole-cell products (HKWCPs) of probiotic Pseudomonas aeruginosa VSG2 strain in stimulating the cytokine responses in the head kidney (HK) macrophages of Labeo rohita. The HK macrophages were incubated with HKWCPs or lipopolysaccharide (LPS), and the responses of cytokine genes, namely interleukin-10 (IL-10), IL-1ß, IL-p35, IL-12p40, tumour necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), interferon-alpha (IFN-α), and interferon-gamma (IFN-γ) were assessed by quantitative real-time PCR (qRT-PCR) at 2, 8, 16, 24, 48, 72 h post-stimulation (hps). Among proinflammatory cytokines, significantly higher expression of IL-1ß and TNF-α was observed at 8-24 hps, and 2-16 hps with HKWCPs, respectively, as compared to controls. However, COX-2 and NF-κB displayed strong expression (P < 0.05) at 2-8 hps, and 8, 16 and 72 hps with HKWCPs, respectively. Antiviral cytokines IFN-α and IFN-γ displayed strong expression (P < 0.05) at 8-24 hps, and 2, 24 and 48 hps with HKWCPs, respectively. Expressions of cell-mediated immune factor genes (IL-12p35 and IL-12p40) were also significantly upregulated at various time points, except IL-12p40 at 72 hps, in HK macrophages stimulated with HKWCPs. Expression of the anti-inflammatory cytokine IL-10 was upregulated (P < 0.05) at 2-24 hps HKWCPs, compared to controls. Enhanced cellular (phagocytic activity and superoxide anion production) and humoral (lysozyme) immune parameters of treated HK macrophages confirmed the induction of inflammatory response. Thus, our results indicated that HKWCPs of probiotic P. aeruginosa VSG2 had greater potential for stimulating the in vitro expression of cytokines in fish and that these HKWCPs may be used as vaccine adjuvants in aquaculture.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process

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[PMID]: 26868214
[Au] Autor:Zhu Q; Li C; Yu ZX; Zou PF; Meng QX; Yao CL
[Ad] Address:Fisheries College/Fujian Provincial Key Laboratory of Marine Fishery Resources and Eco-environment, Jimei University, Xiamen 361021, PR China....
[Ti] Title:Molecular and immune response characterizations of IL-6 in large yellow croaker (Larimichthys crocea).
[So] Source:Fish Shellfish Immunol;50:263-73, 2016 Mar.
[Is] ISSN:1095-9947
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine which exists in multiple tissues and cell lines. In the present study, the full-length cDNA and the genomic sequence of IL-6 (LcIL-6) were cloned from large yellow croaker, Larimichthys crocea. The full-length cDNA of LcIL-6 was 1066 base pairs (bp), containing an open reading frame (ORF) of 678 bp encoding for 225 amino acids, a 5' untranslated region (UTR) of 71 bp and a 3' UTR of 317 bp. The predicted LcIL-6 protein included a 24 amino acids (aa) signal peptide and a conserved IL-6 domain. However, the polypeptide sequence identities between LcIL-6 and its counterparts in mammals and other fish are from 12% to 45%. The genome sequence of LcIL-6 gene was composed of 2126 bp, including five exons and four introns. Phylogenetic analysis revealed that LcIL-6 showed a close relationship with the IL-6 from other bony fish. Quantitative real-time PCR (qRT-PCR) analysis revealed that LcIL-6 mRNA was expressed in most examined tissues, with the most predominant expression in stomach, followed by blood and very weak expression in other tissues. The expression levels of LcIL-6 after challenged with LPS, poly I:C and Vibrio parahaemolyticus were investigated in spleen, head-kidney and liver. LcIL-6 transcripts were induced significantly after immune challenge, with the peak-value of 33.5 times as much as the control in the head-kidney at 3 h after LPS injection (p < 0.05). Overexpression of LcIL-6 enhanced tumor necrosis factor (TNF)-α transcripts significantly (p < 0.05) in L. crocea kidney (LCK) cells. Additionally, recombinant LcIL-6 mature peptide was obtained in the supernatant of Escherichia coli BL21 (DE3). The purified recombinant LcIL-6 fusion protein was also demonstrated to improve the transcriptional expression levels of TNF-α significantly in LCK cells (p < 0.05). However, no significant changes of Mx (myxovirus resistant protein), IL-1ß, janus kinase (JAK)2, signal transducers and activators of transcription (STAT)3 and STAT5 in LCK cells was detected after LcIL-6 overexpression or recombinant LcIL-6 protein stimulation. Our results indicated that LcIL-6 might be important in large yellow croaker immune response and improve the inflammatory response by through activation TNF-α expression.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Process


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