On the cover, the tumor interstitial fluid (TIF) that perfuses breast invasive ductal carcinomas was analyzed using gel-based proteomics, Western immunoblotting, and cytokine antibody arrays (RayBiotech, Inc. Norcross, GA, USA) . The TIF was found to be composed of more than 1,000 proteins–either secreted, shed by membrane vesicles, or leaked due to cell death–produced by the complex network of cell types that make up the tumor microenvironment. For details, see the article by Celis et al., Molecular Cellular Proteomics. April 2004; 11(3):328-39.

Reference List

LPS induces the interaction of a transcription factor, LPS-induced TNF-a factor, and STAT6(B) with effects on multiple cytokines. Xiaoren Tang, Deborah Levy Marciano, Susan E. Leeman and Salomon Amar. PNAS. April 5, 2005 vol. 102 no. 14 5132-5137 "...In this study, analysis by means of a RayBio cytokine antibody array (RayBiotech, Inc. Norcross, GA) demonstrated that the LITAFSTAT6(B) complex significantly up-regulated GRO, IL-1 alpha, RANTES,TNF-alpha, IFN-Gamma, MCP-2, and IL-10.

HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy. Yan Xu, Joseph Kulkoshy, Roger j. Pomerantz.  PNAS. 2004 May 4, 2004 Vol. 101 No. 18.   "...A human protein cytokine-array kit was purchased from RayBiotech (Norcross, GA). Briefly, the membranes were blocked with a blocking buffer, and then 1 ml of medium from either infected or noninfected macrophage or T lymphocyte cultures was added and incubated at room temperature for 2 h..."

Bacteriolytic therapy can generate a potent immune response against experimental tumors. PNAS. October 19, 2004 vol. 101 no. 42 "...... The RayBio Mouse Cytokine Array II was. purchased from RayBiotech (Norcross, GA) and used according. to the manufacturer’s instructions. ...."

Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA. Eur. Journal of Immunology. 2005. 35: 1557–1566  "..... The results were obtained using the RayBio Human Cytokine Array III. PBMC were incubated. in medium, with b-Gal RNA or with b-Gal RNA-protamine ..."

Paneth Cell Cryptdins Act in Vitro as Apical Paracrine Regulators of the Innate Inflammatory Response. Patricia W. Lin, Peter O. Simon, Andrew T. Gewirtz, Andrew S. Neish, Andre J. Ouellette, James L. Madara, and Wayne I. Lencer J. Biol. Chem., Vol. 279, Issue 19, 19902-19907, May 7, 2004   "... ... RayBioTM Inflammation Antibody Array Analysis—After 5 h agonist treatment ..."

Mycobacterium avium 104 deleted of the methyltransferase D gene by allelic replacement lacks serotype-specific glycopeptidolipids and shows attenuated virulence in mice Elzbieta Krzywinska1, Sanchita Bhatnagar, Lindsay Sweet1, Delphi Chatterjee2 and Jeffrey S. Schorey Molecular Microbiology Volume 56 Issue 5 Page 1262  - June 2005   "... isogenic strains were obtained using mouse cytokine array membranes (RayBio®,RayBiotech Norcross, GA, USA) according to the manufacturer's protocol. ..."

The LPA2 receptor mediates mitogenic signals in human colon cancer cells. Am J Physiol Cell Physiol. February 23, 2005. doi:10.1152/ajpcell.00610.2004 "...we treated Caco-2 cells with 10 µM LPA for 5 hrs. The medium was applied to the Human Inflammatory Antibody Array III (RayBiotech: Norcross, GA)."

Recurrent transverse myelitis following neurobrucellosis: Immunologic features and beneficial response to immunosuppression. Chitra Krishnan, Adam I Kaplin, Jerome S Graber, Jessica S Darman, and Douglas A Kerr. Journal of NeuroVirology, 11: 225–231, 2005.  "...cytokine antibody arrays were purchased (RayBio Human Cytokine Antibody Array V— H0108005, 79 cytokines detected;RayBiotech, Inc., Norcross, GA) and carried out according to the manufacturer’s recommendations. A total of 1000 µl of CSF"

Interleukin-12 driven primary hypothyroidism: the contrasting roles of two Th1 cytokines (IL-12 and IFN-alpha). Hiroaki Kimura, Shey-Cherng Tzou, Roberto Rocchi, Patrizio Caturegli. Endocrinology, first published April 28, 2005 ".....detect the greatest number of cytokines with the smallest volume of serum, were purchased from RayBiotech (Norcross, GA). The array allows for the simultaneous detection....."

Effects of Gentianine on the Production of Pro-inflammatory Cytokines in Male Sprague-Dawley Rats Treated with Lipopolysaccharide (LPS) Biol. Pharm. Bull. 28(4) 750—753 (2005) "...LPS markedly increased the production of two pro-inflammatory cytokines (TNF- a and IL-6) and those increased production was specifically inhibited by gentianine...."

Synergistic increases in intracellular Ca(2+), and the release of MCP-1, RANTES, and IL-6 by astrocytes treated with opiates and HIV-1 Tat. GLIA. 2005 Apr 15;50(2):91-106. "...astrocyte cultures treated with morphine and Tat showed exaggerated increases in chemokine release, including monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted (RANTES), as well as interleukin-6 (IL-6)...."

Bone Marrow Stroma Influences Transforming Growth Factor-β Production in Breast Cancer Cells to Regulate c-myc Activation of the Preprotachykinin-I Gene in Breast Cancer Cells. Hyun S. Oh, Anabella Moharita… Pranela Rameshwar. CANCER RESEARCH. 64, 6327-6336, September 1, 2004.   "...Human Cytokine protein array II was purchased from from RayBiotech, Inc… Membranes were incubated with fresh culture media, culture supernatants, cell extracts, or culture supernatants +cell extracts..."

Recombinant Herpes Simplex Virus Type 1 (HSV-1) Codelivering Interleukin-12p35 as a Molecular Adjuvant Enhances the Protective Immune Response against Ocular HSV-1 Challenge JOURNAL OF VIROLOGY. Mar. 2005 Vol. 79, No. 6.   "... Three weeks after the third immunization, spleens from immunized mice were removed aseptically, and single cell suspensions were prepared…. Cell-free culture supernatants were assayed for 32 different cytokines and chemokines by using a mouse cytokine antibody array, (Ray Biotech, Norcross, Ga.)...."

Dysregulated Inflammatory Response to Candida albicans in a C5-Deficient Mouse Strain.  Alaka Mullick, Miria Elias, Serge Picard, Philippe Gros.  Infection and Immunity, Oct. 2004, p. 5868-5876, DOI: 10.1128/IAI.72.10.5868-5876.2004   "... determination of 32 cytokines and chemokines was carried out on serum and peritoneal exudates with RayBio Mouse Cytokine Array II...."

Leukotriene B4 Strongly Increases Monocyte Chemoattractant Protein-1 in Human Monocytes Li Huang, Annie Zhao, Frederick Wong, Julia M. Ayala, Jisong Cui Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1783-1788.   " ... cell free supernatant was collected and hybridized with the membrane blot of human cytokine array that contains 79 human cytokines/chemokines.  Compared with the vehicle-treated control LTB4 induced expression of MCP-1 protein...RayBio Human Cytokine Array V... "

Human CD1d-unrestricted NKT cells release chemokines upon Fas engagement. Martin Giroux and François Denis. Yan Xu, Joseph Kulkoshy, Roger j. Pomerantz.  Blood. prepublished online September 2, 2004; DOI 10.1182/blood-2004-04-1537   "...To evaluate chemokine release, 2.5 x 105 CD56+CD3+ cells were treated for 2 h at 37ºC with 100 ng/ml of sFasL with 3 µg/ml of enhancer or control antibody in 3 ml. The supernatants were analyzed with the RayBio Human Cytokine Antibody Array C Series 1000 (RayBiotech) that allows to detect 34 different chemokines..."

Monitoring the response of orthotopic bladder tumors to granulocyte macrophage colony-stimulating factor therapy using the prostate-specific antigen gene as a reporter. Wu Q, Esuvaranathan K, Mahendran R.  Clinical Cancer Research. 2004 Oct 15; 10(20):6977-84.   "...Cytokine array analysis revealed that GM-CSF gene therapy induced the production of other cytokines and chemokines. CONCLUSIONS: MB49 cells modified to secrete PSA are a reliable method to evaluate therapeutic modalities for bladder cancer...."

Neuroglial activation and neuroinflammation in the brain of patients with autism (p NA).  Diana L. Vargas, Caterina Nascimbene, Chitra Krishnan, Andrew W. Zimmerman, Carlos A. Pardo. Annals of Neurology. 2005 Jan 1; DOI: 10.1002/ana.20315 "...To further characterize the nature of the inflammatory responses in autistic brains, we studied the relative expression of 79 proteins: cytokines associated with innate and adaptive immunity, chemokines, and growth and differentiation factors by human cytokine protein array methods.27,28 Human cytokine array kits (5.1 and V; Raybiotech, Norcross, GA) were used, consisting of 79 different cytokines, chemokines, and growth factors (Table 4) imprinted on a nitrocellulose membrane..."

Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its LPS or its FimA. Qingde Zhou, Tesfahun Desta, Dana T. Graves and Salomon Amar.  Infection and Immunity (IAI). 2005 Feb;73(2):935-43..   "...Culture samples were analyzed with cytokine antibody array using either RayBio Human Cytokine Antibody Array V or RayBio Mouse Cytokine Antibody Array III (RayBiotech, Inc., Norcross, GA)...

Veto-like activity of mesenchymal stem cells: functional discrimination between cellular responses to alloantigens and recall antigens. Rameshwar P. Journal of Immunology. 2003 Oct 1;171(7):3426-34. "...The human cytokine protein array II was purchased from RayBiotech (Norcross, GA) and used according to the manufacturer’s instructions. Briefly, membranes were incubated for 30 min in 5% BSA in 0.01 M Tris buffer with 0.15 M NaCl, pH 7.6..."

Cytokine responses elicited in endothelial cells after treatment with a specific toxin. Jaya Pandey. BioCompare Product Review. May 13, 2004 "...While looking around for the right product, I came across the cytokine antibody array by RayBiotech. Since proteins execute all cell functions, it is more beneficial to look at the protein level than at the mRNA level. Raybiotech has, for the first time, come up with a protein array that is convenient to use..."

Proteomic Characterization of the Interstitial Fluid Perfusing the Breast Tumor Microenvironment. A Novel Resource for Biomarker and Therapeutic Target Discovery. Julio E. Celis, Pavel Gromov, Teresa Cabezón, José M. A. Moreira, Noona Ambartsumian, Kerstin Sandelin, Fritz Rank, and Irina Gromova. Molecular Cellular Proteomics. April 2004; 11(3):328-39. "...Detection of multiple cytokines present in TIFs was done using array-based technology. For this purpose, RayBioTM Cytokine Antibody Arrays 5.1 were purchased from RayBiotech, Inc. (Atlanta, GA)..."

Increased Expression and Secretion of Interleukin-6 in Patients with Barrett’s Esophagus.. Katerina Dvorakova, Harinder Garewal Clinical Cancer Research. 2004 Mar 15;10(6):2020-8. "...In a preliminary study, the secretion of various cytokines into conditioned media from duodenum, BE, and normal squamous esophageal epithelium was evaluated in four BE patients using Human Cytokine Protein Array II obtained from RayBiotech, Inc. (Norcross, GA) according to the manufacturer’s protocol. This assay can simultaneously detect 43 different cytokines with high specificity..."

Antibody array-generated profiles of cytokine release from THP-1 leukemic monocytes exposed to different amphotericin B formulations. Turtinen LW, Prall DN, Bremer LA, Nauss RE, Hartsel SC. Antimicrobial Agents Chemotherapy. 2004 Feb;48(2):396-403. "...Human Cytokine Array I (Ray Biotech Inc., Norcross, Ga.) consisted of 23 different cytokine and chemokine antibodies spotted in duplicate onto a membrane..."

Effects of Gentianine on the Production of Pro-inflammatory Cytokines in Male Sprague-Dawley Rats Treated with Lipopolysaccharide (LPS). Wie-Jong KWAK,a,b Joo-Hyon KIM,a Keun-Ho RYU,a Yong-Baik CHO,a Sun-Duck JEON,a and Chang-Kiu MOON* Biol. Pharm. Bull. 28(4) 750—753 (2005). "...antibody array was performed to detect the cytokines, of which production was changed in the sera from the rats treated with gentianine followed by LPS challenge...LPS markedly increased the production of two pro-inflammatory cytokines (TNF- a and IL-6)..."

Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and protaglandin e(2) secretion in patients with breast cancer".  Pockaj BA, Basu GD. Annals of Surgical Oncology. 3:327-344, 2004. "...A cytokine/chemokine array kit (Ray Biotech Inc., Norcross, GA) was used to detect a panel of 22 secreted cytokines and chemokines in the serum from healthy patients and those with breast cancer..."

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells. Katherine L Meyer-Siegler, BMC Cancer. 2004, 4:34. "...An array for secreted human cytokine proteins (Human Cytokine Array V, RayBio, Norcross, GA) was used to determine relative changes in secreted cytokines..."

The malaria metabolite hemozoin initiates proinflammatory signaling via a MyD88- dependent pathway.International Congress of Immunology. 2004 July W23-81. "...C57/Bl6 mice were injected i.p. with either 2 ml of saline or 2 ml of 4mg/ml hemozoin in saline (n=4 for each group). The serum was collected via cardiac puncture, pooled and then subjected to cytokine array analysis according to manufactures instructions (Raybiotech)..."

In Vivo Proteomic Analysis of Cytokine Expression in Laser Capture-Microdissected Urothelial Cells of Obstructed Ureteropelvic Junction Procured by Laparoscopic Dismembered Pyeloplasty. Journal of Endourology. 2003 June; Volume:17 Number:5 Page:333--336. "...Differential expression profile analysis of cytokines in normal and hyperplastic cells was performed using a human cytokine protein chip (RayBiotech, Norcross, GA)..."

Distinct Cytokine Release Profiles from Human Endothelial and THP-1 Macrophage-like Cells Exposed to Different Amphotericin B Formulations. Lloyd W. Turtinen, Lindsay A. Bremer, David N. Prall, Jenifer Schwartzhoff, Scott C. Hartsel, Taylor & Francis. Volume 27, Number 1 / 2005  "......43 cytokine antibody pairs plus controls; RayBio Array III). ... multiple cytokines by protein arrays from cell lysate and tissue lysate. Clin. ..."

Cytokine Antibody Arrays: A Promising Tool to Identify Molecular Targets for Drug Discovery.  Huang, Combinatorial Chemistry & High Throughput Screening. 2003, 6,79-99  "...RayBiotech, Inc, which develops and produces protein array technology..."

Identification of Extracellular and Intracellular Signaling Components of the Mammary Adipose Tissue and Its Interstitial Fluid in High Risk Breast Cancer Patients.  Julio E. Celis, José M. A. Moreira,, Teresa Cabezón,, Pavel Gromov,, Esbern Friis,||, Fritz Rank, and Irina Gromova Molecular & Cellular Proteomics 4:492-522, 2005 "...... Cytokines present in FIFs were detected using the RayBio® Human Cytokine Array C Series ....."

Phenotype and function of a CD56+ peripheral blood monocyte.  G Sconocchia, K Keyvanfar, F El Ouriaghli, M Grube, K Rezvani, H Fujiwara, J P McCoy, N Hensel, A J Barrett Leukemia 19, 69-76 (01 Jan 2005) "...supernatants were assessed for cytokine content in a 42 human cytokine array system (RayBiotech Inc., Norcross, GA, USA), which detects the antibody–cytokine sandwich by..."

K.S. Rosenthal, N.Goel, R. Singavarapu, D.H. Zimmerman. Cel-1000 protects mice against HSV-1 challenge by stimulating IL-2 production. Abstract published in abstract book of Interscience Conference on Antimicrobial Agents and Chemotherapy held in Chicago during Sept14-17, 2003. "...Cytokines were assayed with a cytokine array system (RayBiotech). Monoclonal antibodies (1mg/day for 5 days) were used to ablate CD4 or CD8 expressing cells or interferon gamma (IFN?) either prior to CEL-1000 treatment or virus challenge to determine their role in CEL-1000 action...."

Impact of proteomics on bladder cancer research. Julio E Celis, Irina Gromova­. Pharmacogenomics, June 2004, Vol. 5, No. 4, Pages 381-394  "...... The RayBio™ Cytokine Antibody Arrays 5.1 was obtained from RayBiotech, USA. Antibodies present in the table are listed above the. arrays. ..."

Bone Marrow Mesenchymal Stem Cells Provide an Alternate Pathway of Osteoclast Activation and Bone Destruction by Cancer Cells. Yasuyoshi Sohara, Hiroyuki Shimada, Cedric Minkin, Anat Erdreich-Epstein, Jan A. Nolta and Yves A. DeClerck. Cancer Research 65, 1129-1135, February 15, 2005.  "...... cells and bone marrow mesenchymal stem cells was done using the  RayBio Cytokine Antibody Array kit of ..." pan

G-CSF-mobilized CD34+ cells cultured in interleukin-2 and stem cell factor generate a phenotypically novel monocyte. Giuseppe Sconocchia1, Hiroshi Fujiwara, Katayoun Rezvani, Keyvan Keyvanfar, Frank El Ouriaghli, Matthias Grube, Jos Melenhorst, Nancy Hensel and A. John Barrett. Journal of Leukocyte Biology. 2004;76:1214-1219.  "...... cytokine array system RayBio. TM. (RayBiotech, Norcross, GA), which detects. the antibody-cytokine sandwich by chemiluminescence. ..."

Adenosine-Activated Mast Cells Induce IgE Synthesis by B Lymphocytes: An A2B-Mediated Process Involving Th2 Cytokines IL-4 and IL-13 with Implications for Asthma. Sergey Ryzhov, Anna E. Goldstein, Anton Matafonov and Igor Feoktistov. The Journal of Immunology, 2004, 172: 7726-7733.  "...... at 4°C. Secreted cytokines were assayed with RayBio Human Cytokine Array III (RayBiotech, Norcross, GA) in accordance with manufacturer’s instructions. ..."

Attenuation of Th1 Effector Cell Responses and Susceptibility to Experimental Allergic Encephalomyelitis in Histamine H2 Receptor Knockout Mice Is Due to Dysregulation of Cytokine Production by Antigen-Presenting Cells. Cory Teuscher*, Matthew E. Poynter*, Halina Offner, Alex Zamora, Takeshi Watanabe, Parley D. Fillmore, James F. Zachary and Elizabeth P. Blankenhorn. American Journal of Pathology. 2004;164:883-892.).   "...... In some experiments cytokine production was assessed using RayBio Mouse Cytokine Array 1 (RayBiotech, Inc., Norcross, GA). ..."

Towards discovery-driven translational research in breast cancer. Julio E. Celis, José M. A. Moreira and Pavel Gromov FEBS Journal, Volume 272 Issue 1 Page 2  - January 2005 "..... (A) Cytokine-specific antibody arrays (RayBio® human cytokine array ... [Full Size]. Fig. 4. IHC of nonmalignant epithelial cells (A) and tumour cells ..."

Effect of Cognate Human CD4+ T Cell and Endothelial Cell Interactions Upon Chemokine Production. Tay, Szun S.; McCormack, Ann; Rose, Marlene L Transplantation. 78(7):987-994, October 15, 2004 "..... ... Measurement of Chemokines Using the RayBio Cytokine Array TOP. Secretion of chemokine into supernatants was measured using the RayBio Human Cytokine ..."

Lack of Stringent Serum Requirement in Growth of Oral Mucosal Fibroblasts Derived from Diabetic Patients. Q. ZHANG, Y. WU, M. CHAN, A.P. KELLY, D.V. MESSADI, and A.D. LE. Seq #73 - Mucosal Biology - Epithelial Biology, Wound Healing and Angiogenesis  11:00 AM-12:15 PM, Thursday, 26 June 2003 Svenska Massan Exhibition Hall B "...... A panel of 36 cytokines will be used to screen differentially expressed protein products using RayBio Human Cytokine Array (RayBiotech Inc., GA). ...".

Protein array analysis of peripheral/central cytokine levels in rats. W. GUO, S.-P. ZOU, S. SUGIYO, R. DUBNER, and K. REN Seq #122 - Basic Sensory Mechanisms and Molecular Studies 10:15 AM-11:30 AM, Thursday, 11 March 2004 Hawaii Convention Center Exhibit Hall 1-2   "...... Rat cytokine array membranes coated with 19 specific cytokine antibodies (RayBio) were probed with isolated protein samples and the relative cytokine ..."

LPS induces the interaction of a transcription factor, LPS-induced TNF-a factor, and STAT6(B) with effects on multiple cytokines. Xiaoren Tang, Deborah Levy Marciano, Susan E. Leeman and Salomon Amar. PNAS. April 5, 2005 vol. 102 no. 14 5132-5137 "...In this study, analysis by means of a RayBio cytokine antibody array (RayBiotech, Inc. Norcross, GA) demonstrated that the LITAFSTAT6(B) complex significantly up-regulated GRO, IL-1 alpha, RANTES,TNF-alpha, IFN-Gamma, MCP-2, and IL-10.

HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy. Yan Xu, Joseph Kulkoshy, Roger j. Pomerantz.  PNAS. 2004 May 4, 2004 Vol. 101 No. 18.   "...A human protein cytokine-array kit was purchased from RayBiotech (Norcross, GA). Briefly, the membranes were blocked with a blocking buffer, and then 1 ml of medium from either infected or noninfected macrophage or T lymphocyte cultures was added and incubated at room temperature for 2 h..."

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Y. Lin, Ruochun Huang, Li-Pai Chen, Henry Lisoukov, Zhen-Hai Lu, Shiyong Li, Cheng C. Wang and R.-P. Huang. (2003) Profiling of cytokine expression by biotin-labeled-based protein arrays. Proteomics.3: 1750-1757.

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