News Article | May 18, 2017
Company pivots focus onto FAIMS Technology for new commercial applications VANCOUVER, BC--(Marketwired - May 18, 2017) - Breathtec BioMedical, Inc. ( : BTH) ( : BTH) ( : BTI) ( : BTHCF) (the "Company" or "Breathtec"), a medical diagnostics company focused on developing, in-licensing and commercializing proprietary, innovative breath analysis devices for the early detection of infectious and life threatening diseases, wishes to address recent corporate events and to provide an update regarding its immediate outlook and future plans. The Company is pleased to announce the formation of a new strategic alliance and research agreement with ZeptoMetrix™ Corporation, an industry leader and innovator for Infectious Disease Diagnostics and Development. Plans include an exploratory study to identify biomarkers associated with the Zika virus. The Company views the development of portable devices designed to screen individuals who may carry infections such as Zika at international points of entry as a significant opportunity for its technology. This is a new and exciting area of interest for the Company as current tests for infectious diseases are expensive and often require time consuming lab testing delays. "Our extensive experience and expertise in propagation and purification of infectious disease cultures will be a tremendous asset in this relationship," states Dr. Gregory R. Chiklis, President and CEO of ZeptoMetrix Corporation. "I am excited and pleased in what both ZeptoMetrix™ and Breathtec are committed to bringing to this alliance in order to help provide patients with proper results." Concurrently, Breathtec continues to progress its flagship FAIMS technology with advanced performance testing of its V2 prototype nearing completion. Updates to the system have increased sensitivity and resolution of the device and refinements to circuit design, ionization source and square wave generation. These improvements are subjects of new and important intellectual property scheduled for patent applications as added value opportunities for the Company. Additional efforts include design and fabrication of a clinically optimal breath intake system anticipated to undergo testing in June. As advancements are made, the Company continues to expand investigations into new avenues for future widespread commercial adoption. In related news, Breathtec welcomes the appointment of Mr. Alfred Wong as Vice President, Corporate Development and Communications. Mr. Wong is an experienced business development professional in the capital markets, technology, logistics, and waste management sectors. He has extensively consulted with early stage startup companies on the development of business plans, management recruitment, transaction negotiation, mergers & acquisitions, and related business development matters. Breathtec also announced today that Mr. Kal Malhi has resigned his positions as President and Director of the Company to pursue other interests. Breathtec thanks Mr. Malhi for his services and wishes him well on his future endeavors, and further advises that its CEO, Mr. Guy LaTorre now also serves in the role of President. In a related announcement pursuant to the Company's stock option plan, 700,000 incentive stock options exercisable at $0.15 per share for a period of five years have been granted to directors, officers and consultants of the Company. Moving ahead, and pursuant to its strategic goals and ongoing commitment to shareholder value, Company management has determined to solely dedicate its resources and efforts towards the advancement of its High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) technology. As a result, the Company and licensor advise their intent to mutually terminate the proposed licensing agreement for the NaNose electronic nose technology. The Company feels the advancement of the FAIMS technology platform and its associated exclusive licensing agreement and broad applicability for medical diagnostics worldwide, offers far greater incentives for commercialization of this singularly promising technology platform. As a result, plans for a clinical study of NaNose previously announced for Surrey, Canada will cease, and resources will be redirected to begin a clinical evaluation process of the FAIMS technology, which is currently scheduled to commence later this year. ON BEHALF OF THE BOARD "Guy LaTorre" CEO, President & Director ABOUT ZEPTO METRIX™ Founded in 1999 and headquartered in Buffalo, New York with additional facilities in Franklin, Massachusetts, ZeptoMetrix is a fully integrated biotechnology company, whose products and services support all phases of research & development, validation, manufacturing and commercialization of diagnostic tests. Find out more at www.zeptometrix.com. ABOUT BREATHTEC BIOMEDICAL INC. ( : BTH) ( : BTHCF) Breathtec Biomedical, Inc. ("Breathtec") was formed to propel innovative research in the area of airborne analysis as a medical screening tool. Our efforts are aimed at leading the development of commercially viable methods for the early screening of certain pathogens. Our primary avenue of investigation is focused on innovation and advances in the field of specialized mass spectrometry. For more information: www.breathtecbiomedical.com. CAUTIONARY DISCLAIMER STATEMENT: No Securities Exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to product development, licensing, commercialization and regulatory compliance issues and other statements that are not historical facts. Forward-looking statements are often identified by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company's expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law.
News Article | December 14, 2016
No statistical methods were used to predetermine sample size. The experiments were not randomized and the investigators were not blinded to allocation during experiments and outcome assessment. Human skin tissue was obtained from healthy donors undergoing corrective breast or abdominal surgery after informed consent in accordance with our institutional guidelines. This study was approved by the Medical Ethics Review Committee of the Academic Medical Center. Split-skin grafts of 0.3 mm in thickness were obtained using a dermatome (Zimmer). After incubation with Dispase II (1 U ml−1, Roche Diagnostics), epidermal sheets were separated from the dermis and cultured in in Iscoves Modified Dulbeccos’s Medium (IMDM, Thermo Fischer Scientific) supplemented with 10% FCS, gentamycine (20 μg ml−1, Centrafarm), pencilline/streptomycin (10 U ml−1 and 10 μg ml−1, respectively; Invitrogen). Further LC purification was performed using a Ficoll gradient (Axis-shield) and CD1a microbeads (Miltenyl Biotec) as described before4, 10. Isolated LCs were routinely 90% pure and expressed high levels of Langerin and CD1a. MUTZ-LCs were differentiated from CD34+ human AML cell line MUTZ3 progenitors in the presence of GM-CSF (100 ng ml−1, Invitrogen), TGF-β (10 ng ml−1, R&D) and TNF-α (2.5 ng ml−1, R&D) and cultured as described before14. Immature DCs were differentiated from monocytes, isolated from buffy coats of healthy volunteer blood donors (Sanquin, The Netherlands), in the presence of IL-4 (500 U ml−1, Invitrogen) and GM-CSF (800 U ml−1, Invitrogen) and used at day 6 or 7 as previously described20. CD4+ T cells were obtained from peripheral blood mononuclear cells (PBMCs) activated with phytohaemagglutinin (1 mg ml−1; L2769, Sigma Aldrich) for 3 days, enriched for CD4+ T cells by negative selection using MACS beads (130-096-533, Miltenyi) and cultured overnight with IL-2 (20 U ml−1; 130-097-745, Miltenyi) as described before5. The following inhibitors were used: rapamycin (mTOR inhibitor, tlrl-rap, Invivogen), bafilomycin A1 (V-ATPase inhibitor; tlrl-baf1; Invivogen) and MG-132 (proteasome inhibitor; 474790; Calbiochem). All cell lines were obtained from ATCC and tested negative for mycoplasma contamination, determined in 3-day-old cell cultures by PCR. Langerin and Langerin mutant W264R expression plasmid pcDNA3.1 were obtained from Life Technologies and subcloned into lentiviral construct pWPXLd (Addgene). HIV-1-based lentiviruses were produced by co-transfection of 293T cells with the lentiviral vector construct, the packaging construct (psPAX2, Addgene) and vesicular stomatitis virus glycoprotein envelope (pMD2.G, Addgene) as described previously31. U87 cell lines stably expressing CD4 and wild-type CCR5 co-receptor (obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: U87 CD4+CCR5+ cells from H. K. Deng and D. R. Littman32) were transduced with HIV-1-based lentiviruses expressing sequences coding human TRIM5α33, rhesus TRIM5α33, wild-type Langerin or Langerin(W264R). NL4.3, NL4.3-BaL, SF162, NL4.3eGFP-BaL, NL4.3-BlaM-Vpr and VSV-G-pseudotyped NL4.3(ΔEnv) HIV-1 were generated as described10. All produced viruses were quantified by p24 ELISA (Perkin Elmer Life Sciences) and titrated using the indicator cells TZM-Bl. Primary LCs and MUTZ-LCs were infected with a multiplicity of infection of 0.2–0.4 and HIV-1 infection was assessed by flow cytometry at day 7 after infection by intracellular p24 staining. Double staining with CD1a (LCs marker; HI149-APC; BD Pharmigen) and p24 (KC57-RD1-PE; Beckman Coulter) was used to discriminate the percentage of CD1a+p24+ infected LCs. CD4+CCR5+ U87 parental or transduced cells were infected at a multiplicity of infection of 0.1–0.2 and HIV-1 infection was assessed at day 3 after infection by intracellular p24 staining or GFP expression. For analysis of transmission of HIV-1 to T cells, LCs were stringently washed 3 days after infection followed by co-culture with activated allogeneic CD4+ T cells for 3 days. Triple staining with CD1a (LCs marker), CD3 (T cells marker; 552851-PercP, BD Pharmigen) and p24 was used to discriminate the percentage of CD3+CD1a−p24+ infected T cells. HIV-1 infection and transmission was assessed by FACSCanto II flow cytometer (BD Biosciences) and data analysis was carried out with FlowJo software (Treestar). HIV-1 production was determined by a p24 antigen ELISA in culture supernatants (ZeptoMetrix). mRNA was isolated with an mRNA Capture kit (Roche) and cDNA was synthesized with a reverse-transcriptase kit (Promega). For real-time PCR analysis, PCR amplification was performed in the presence of SYBR green in a 7500 Fast Realtime PCR System (ABI). Specific primers were designed with Primer Express 2.0 (Applied Biosystems; Extended Data Table 1). The cycling threshold (C ) value is defined as the number of PCR cycles in which the fluorescence signal exceeds the detection threshold value. For each sample, the normalized amount of target mRNA (N ) was calculated from the C values obtained for both target and household (GAPDH, primary LCs, DCs and U87 cells lines; β-actin, MUTZ-LCs) mRNA with the equation N = 2Ct(control) − Ct(target). For relative mRNA expression, control siRNA sample was set at 1 within the experiment and for each donor. A two-step Alu-long terminal repeat (LTR) PCR was used to quantify the integrated HIV-1 DNA in infected cells as previously described20. Total cell DNA was isolated at 16 h after infection (multiplicity of infection of 0.4) with a QIAamp blood isolation kit (Qiagen). In the first round of PCR, the DNA sequence between HIV-1 LTR (LTR R region, extended with a marker region at the 5′ end) and the nearest Alu repeat was amplified (primer sequences, Extended Data Table 1). The second round was nested quantitative real-time PCR of the first-round PCR products using primers annealing to the aforementioned marker region in combination with another HIV-1-specific primer (LTR U5 region) by real-time quantitative PCR. Two different dilutions of the PCR products from the first-round of PCR were assayed to ensure that PCR inhibitors were absent. For monitoring the signal contributed by unintegrated HIV-1 DNA, the first-round PCR was also performed using the HIV-1-specific primer (LTR R region) only. HIV-1 integration was normalized relative to GAPDH DNA levels. For relative HIV-1 integration, control siRNA-infected cells (total signal; Supplementary Table 1) was set as 1 for one experiment or for each donor. A BlaM-Vpr-based assay was used to quantify fusion of HIV-1 to the host membrane in infected LCs as previously described10. LCs were infected with NL4.3-BlaM-Vpr for 2 h and then loaded with CCF2/AM (1 mM, LiveBLAzer FRET-B/G Loading Kit, Life technologies) in serum-free IMDM medium for 1 h at 25 °C. After washing, BlaM reaction was allowed to develop for 16 h at 22 °C in IMDM supplemented with 10% FCS and 2.5 mM anion transport inhibitor probenecid (Sigma Pharmaceuticals). HIV-1 fusion was determined by monitoring the changes in fluorescence of CCF2/AM dye, which reflect the presence of BlaM-Vpr into the cytoplasm of target cells upon viral fusion. The shift from green emission fluorescence (500 nm) to blue emission fluorescence (450 nm) of CCF2/AM dye was assessed by flow cytometer LSRFortessa (BD Biosciences) and data analysis was carried out with FlowJo software. Percentages of blue fluorescent CCF2/AM+ cells are depicted as percentage of HIV-1 fusion. A fluorescent bead adhesion assay was used to examine the ability of HIV-1 gp120-coated fluorescent beads to bind Langerin in CD4+CCR5+ U87 transfectants as previously described5. Binding was measured by FACSCanto II flow cytometer and data analysis was carried out with FlowJo software. Skin LCs and DCs were transfected with 50 nm siRNA with the transfection reagent DF4 (Dharmacon) whereas MUTZ-LCs, CD4+CCR5+ U87 parental or transduced cells were transfected with transfection reagent DF1 (Dharmacon) and were used for experiments 48–72 h after transfection. The siRNA (SMARTpool; Dharmacon) were specific for Atg5, (M-004374-04), Atg16L1 (M-021033), LSP-1 (M-012640-00), TRIM5α (M-007100-00) and non-targeting siRNA (D-001206-13) served as control. Langerin was silenced in MUTZ-LCs by electroporation with Neon Transfection System (ThermoFischer Scientific) using siRNA Langerin (10 μM siRNA, M-013059-01, SMARTpool; Dharmacon). Silencing of the aforementioned targets was verified by real-time PCR, flow cytometer and immunoblotting (Extended Data Figs 1d, e, 2a–k). Cells were pre-treated with bafilomycin A1 for 2 h or left untreated followed by incubation with HIV-1 for 16 h. Quantification of intracellular LC3 II levels by saponin extraction was performed as described before34, 35. LCs were washed in PBS and permeabilized with 0.05% saponin in PBS. Cells were incubated at 4 °C for 30 min with mouse anti-LC3 primary antibody (M152-3; MBL International) or with mouse anti-IgG1 isotype control (MOPC-21; BD Pharmingen) followed by incubation with Alexa Fluor 488-conjugated goat-anti mouse IgG antibody (A-21121, Life Technologies) in saponin buffer. Intracellular LC3 II levels were assessed by FACSScan or FACSCanto II flow cytometers (BD Biosciences) and data analysis was carried out with FlowJo. Cells were pre-treated with bafilomycin for 2 h or left untreated followed by incubation with HIV-1 for 4 h. Quantification of intracellular LC3 II levels by saponin extraction was performed as described before35. Whole-cell extracts were prepared using RIPA lysis buffer supplemented with protease inhibitors (9806; Cell Signalling). 20–30 μg of extract were resolved by SDS–PAGE (15%) and immunoblotted with LC3 (2G6; Nanotools) and β-actin (sc-81178; Santa Cruz) antibodies, followed by incubation with HRP-conjugated secondary rabbit-anti-mouse antibody (P0161; Dako) and luminol-based enhanced chemiluminescence (ECL) detection (34075; Thermo Scientific). For gel source data, see Supplementary Fig. 1. MUTZ-LCs (2 × 106) were incubated for 16 h with HIV-1 NL4.3 (multiplicity of infection, 0.5) or left untreated as a control, fixed in 4% paraformaldehyde and 1% glutaraldehyde in sodium cacodylate buffer for 10 min at room temperature followed by 24 h at 4 °C. After fixation, cells were collected by centrifugation and the pellet was washed in sodium cacodylate buffer. Cells were post-fixed for 1 h at 4 °C (1% osmium tetroxide, 0.8% potassium ferrocyanide in the same buffer), contrasted in 0.5% uranyl acetate, dehydrated in a graded ethanol series and embedded in epon LX112. Ultrathin sections were stained with uranylacetate/lead citrate and examined with a FEI Tecnai-12 transmission electron microscope. Numbers of autophagosomes per cell was determined in 50 cells for each condition counted by two independent researchers. LCs were left to adhere onto poly-l-lysine coated slides. Cells were fixed in 4% paraformaldehyde and permeabilized with PBS/0.1% saponin/1% BSA/1 mM Hepes. Cells were stained with anti-Langerin (AF2088; R&D Systems) and TRIM5α (ab109709; Abcam) antibodies followed by Alexa Fluor 647-conjugated anti-goat (A-21447; Life Technologies) and Alexa Fluor 488-conjugated anti-rabbit (A-21206; Life Technologies). For detection of autophagic vesicles, LCs were pre-loaded with the Cyto-ID Green detection autophagy reagent (ENZ-51031; Enzo Life Sciences), which was previously shown to specifically stain autophagic vesicles36 before adherence to microscope slides and stained with p24 (KC57-RD1-PE; Beckman Coulter) followed by Alexa-Fluor-546-conjugated anti-mouse (A-11003; Life Technologies). Nuclei were counterstained with Hoechst (10 μg ml−1; Molecular Probes). Single plane images were obtained by Leica TCS SP-8 X confocal microscope and data analysis was carried out with Leica LAS AF Lite (Leica Microsystems). Whole-cell extracts were prepared using RIPA lysis buffer supplemented with protease inhibitors. Atg16L1, DC-SIGN, Langerin, p62 and TRIM5α were immunoprecipitated from 40 μg of extract with anti- Atg16L1 (PM040; MBL International), DC-SIGN (AZN-D1)19, Langerin (10E2)5, p62 (ab56416; Abcam), TRIM5α (ab109709; Abcam), mouse IgG1 isotype control (MOPC-21; BD Pharmingen), mouse IgG2a isotype control (IC003A; R&D systems) and rabbit IgG control (sc-2077; Santa Cruz) coated on protein A/G PLUS agarose beads (sc-2003; Santa Cruz), washed twice with ice-cold RIPA lysis buffer and resuspended in Laemmli sample buffer (161-0747, Bio-Rad). Immunoprecipitated samples were resolved by SDS–PAGE (12.5%), and detected by immunoblotting with Atg5 (PM050; MBL), Atg16L1 (MBL), DC-SIGN (551186; BD Biosciences), Langerin (AF2088; R&D Systems), LSP-1 (3812S; Cell Signalling), TRIM5α (Abcam) and HIV-p24 (KC57-RD1-PE; Beckman Coulter) antibodies, followed by incubation with Clean-Blot IP Detection Kit-HRP (21232; Thermo Scientific) and ECL detection (34075; Thermo Scientific). Data acquisition was carried out with ImageQuant LAS 4000 (GE Healthcare). Immunoprecipitation with TRIM5α, Langerin, DC-SIGN, Atg16L1 and p62 pulls-down mostly the TRIM5α (approximately 56 kDa) form. Relative intensity of the bands was quantified using Image Studio Lite 5.2 software by normalizing β-actin and set at 1 in untreated cells. For gel source data, see Supplementary Fig. 1. Two-tailed Student’s t-test for paired observations (differences of stimulations within the same donor or cell-type) or unpaired observation (differences between U87 transfectants). Statistical analyses were performed using GraphPad 6.0 software and significance was set at P < 0.05 (*P < 0.05; **P < 0.01). The data that support the findings of this study are available from the corresponding author upon reasonable request.
News Article | December 2, 2016
United States, EU, Japan, China, India and Southeast Asia Diagnosis and Treatment of Zika Virus Disease Market This report studies the Global Diagnosis and Treatment of Zika Virus Disease Market, analyzes and researches the Diagnosis and Treatment of Zika Virus Disease development status and forecast in United States, EU, Japan, China, India and Southeast Asia. This report focuses on the top players in global market, like Bharat Biotech Inovio Pharmaceuticals and GeneOne Life Sciences Intrexon Cerus Sanofi NewLink Genetics Immunovaccine GlaxoSmithKline ATCC ZeptoMetrix Market segment by Application, Diagnosis and Treatment of Zika Virus Disease can be split into Application 1 Application 2 Application 3 United States, EU, Japan, China, India and Southeast Asia Diagnosis and Treatment of Zika Virus Disease Market Size, Status and Forecast 2021 1 Industry Overview of Diagnosis and Treatment of Zika Virus Disease 1.1 Diagnosis and Treatment of Zika Virus Disease Market Overview 1.1.1 Diagnosis and Treatment of Zika Virus Disease Product Scope 1.1.2 Market Status and Outlook 1.2 Global Diagnosis and Treatment of Zika Virus Disease Market Size and Analysis by Regions 1.2.1 United States 1.2.2 EU 1.2.3 Japan 1.2.4 China 1.2.5 India 1.2.6 Southeast Asia 1.3 Diagnosis and Treatment of Zika Virus Disease Market by End Users/Application 1.3.1 Application 1 1.3.2 Application 2 1.3.3 Application 3 2 Global Diagnosis and Treatment of Zika Virus Disease Competition Analysis by Players 2.1 Diagnosis and Treatment of Zika Virus Disease Market Size (Value) by Players (2015-2016) 2.2 Competitive Status and Trend 2.2.1 Market Concentration Rate 2.2.2 Product/Service Differences 2.2.3 New Entrants 2.2.4 The Technology Trends in Future 3 Company (Top Players) Profiles 3.1 Bharat Biotech 3.1.1 Company Profile 3.1.2 Main Business/Business Overview 3.1.3 Products, Services and Solutions 3.1.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.1.5 Recent Developments 3.2 Inovio Pharmaceuticals and GeneOne Life Sciences 3.2.1 Company Profile 3.2.2 Main Business/Business Overview 3.2.3 Products, Services and Solutions 3.2.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.2.5 Recent Developments 3.3 Intrexon 3.3.1 Company Profile 3.3.2 Main Business/Business Overview 3.3.3 Products, Services and Solutions 3.3.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.3.5 Recent Developments 3.4 Cerus 3.4.1 Company Profile 3.4.2 Main Business/Business Overview 3.4.3 Products, Services and Solutions 3.4.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.4.5 Recent Developments 3.5 Sanofi 3.5.1 Company Profile 3.5.2 Main Business/Business Overview 3.5.3 Products, Services and Solutions 3.5.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.5.5 Recent Developments 3.6 NewLink Genetics 3.6.1 Company Profile 3.6.2 Main Business/Business Overview 3.6.3 Products, Services and Solutions 3.6.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.6.5 Recent Developments 3.7 Immunovaccine 3.7.1 Company Profile 3.7.2 Main Business/Business Overview 3.7.3 Products, Services and Solutions 3.7.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.7.5 Recent Developments 3.8 GlaxoSmithKline 3.8.1 Company Profile 3.8.2 Main Business/Business Overview 3.8.3 Products, Services and Solutions 3.8.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.8.5 Recent Developments 3.9 ATCC 3.9.1 Company Profile 3.9.2 Main Business/Business Overview 3.9.3 Products, Services and Solutions 3.9.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.9.5 Recent Developments 3.10 ZeptoMetrix 3.10.1 Company Profile 3.10.2 Main Business/Business Overview 3.10.3 Products, Services and Solutions 3.10.4 Diagnosis and Treatment of Zika Virus Disease Revenue (Value) (2011-2016) 3.10.5 Recent Developments For more information or any query mail at [email protected]
Roberts J.L.,Virginia Commonwealth University |
Tavallai M.,Virginia Commonwealth University |
Nourbakhsh A.,Virginia Commonwealth University |
Fidanza A.,ZeptoMetrix |
And 8 more authors.
Journal of Cellular Physiology | Year: 2015
Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A. Prolonged 'rafenib/sildenafil treatment killed tumor cells and also rapidly decreased the expression of: the drug efflux pumps ABCB1 and ABCG2; and NPC1 and NTCP, receptors for Ebola/Hepatitis A and B viruses, respectively. Pre-treatment with the 'Rafenib/sildenafil combination reduced expression of the Coxsackie and Adenovirus receptor in parallel with it also reducing the ability of a serotype 5 Adenovirus or Coxsackie virus B4 to infect and to reproduce. Sorafenib/pazopanib and sildenafil was much more potent than sorafenib/pazopanib as single agents at preventing Adenovirus, Mumps, Chikungunya, Dengue, Rabies, West Nile, Yellow Fever, and Enterovirus 71 infection and reproduction. 'Rafenib drugs/pazopanib as single agents killed laboratory generated antibiotic resistant E. coli which was associated with reduced Dna K and Rec A expression. Marginally toxic doses of 'Rafenib drugs/pazopanib restored antibiotic sensitivity in pan-antibiotic resistant bacteria including multiple strains of blakpc Klebsiella pneumoniae. Thus, Dna K is an antibiotic target for sorafenib, and inhibition of GRP78/Dna K has therapeutic utility for cancer and for bacterial and viral infections. © 2015 Wiley Periodicals, Inc.
PubMed | Virginia Commonwealth University and ZeptoMetrix
Type: Journal Article | Journal: Journal of cellular physiology | Year: 2015
Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A. Prolonged rafenib/sildenafil treatment killed tumor cells and also rapidly decreased the expression of: the drug efflux pumps ABCB1 and ABCG2; and NPC1 and NTCP, receptors for Ebola/Hepatitis A and B viruses, respectively. Pre-treatment with the Rafenib/sildenafil combination reduced expression of the Coxsackie and Adenovirus receptor in parallel with it also reducing the ability of a serotype 5 Adenovirus or Coxsackie virus B4 to infect and to reproduce. Sorafenib/pazopanib and sildenafil was much more potent than sorafenib/pazopanib as single agents at preventing Adenovirus, Mumps, Chikungunya, Dengue, Rabies, West Nile, Yellow Fever, and Enterovirus 71 infection and reproduction. Rafenib drugs/pazopanib as single agents killed laboratory generated antibiotic resistant E. coli which was associated with reduced Dna K and Rec A expression. Marginally toxic doses of Rafenib drugs/pazopanib restored antibiotic sensitivity in pan-antibiotic resistant bacteria including multiple strains of blakpc Klebsiella pneumoniae. Thus, Dna K is an antibiotic target for sorafenib, and inhibition of GRP78/Dna K has therapeutic utility for cancer and for bacterial and viral infections.
News Article | October 31, 2016
ZeptoMetrix™ Corporation, an industry leader and innovator for Infectious Disease Diagnostics and Development, announced today a broad, strategic collaboration with HarkerBIO for the development of unique recombinant proteins critical to tropical disease. HarkerBIO, known for its high success rate with challenging protein targets, is a premier partner for pharma and biotech companies with structure based drug discovery programs. Under this broad research, development and commercialization alliance, HarkerBIO (http://www.harkerbio.com) will combine its extensive background in the design and development of various recombinant proteins with ZeptoMetrix™ (http://www.zeptometrix.com), who in turn, will leverage its proficiency for production and commercialization to an anxious global market. The initial release of these new to market recombinant proteins are dedicated specifically to Tropical Disease detection. Presently, Ebola and Zika virus recombinants are prepared for retail sales with Yellow Fever, Lassa Fever, Chikungunya and Dengue viruses to be released in the immediate future. “Today, tropical diseases are a massive global concern," states Dr. Gregory R. Chiklis, President and CEO of ZeptoMetrix Corporation. "I am excited and pleased that both ZeptoMetrix™ and HarkerBIO are committed to bringing accurate, safe and reliable diagnostic tools to market to help provide patients with proper results." Founded in 1999 and headquartered in Buffalo, New York with additional facilities in Franklin, Massachusetts, ZeptoMetrix is a fully integrated biotechnology company, whose products and services support all phases of research & development, validation, manufacturing and commercialization of diagnostic tests. HarkerBio was founded in 2014 as a spin-off of the Hauptman-Woodward Medical Research Institute in Buffalo, NY. The company focuses on enabling its clients and partners to discover, optimize, and study drug candidates through holistic application of structural biology; including protein design, protein production, crystallization, crystallography, and structure determination. For more information, please contact: