LIVIVO - Search results -

Search results

Result 1 - 10 of total 15

Search options

Article ; Online: A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients.

Yamada, Miko / Miller, Dennis M / Lowe, Melinda / Rowe, Casey / Wood, Dominic / Soyer, H Peter / Byrnes-Blake, Kelly / Parrish-Novak, Julia / Ishak, Laura / Olson, James M / Brandt, Gordon / Griffin, Paul / Spelman, Lynda / Prow, Tarl W

Contemporary clinical trials communications

2021 Volume 23, Page(s) 100830

Abstract: BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics ...

Abstract	BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers. Doses were 1, 3, 6, 12, and 18 mg, with 3-6 patients/cohort. Fluorescence imaging was conducted before and up to 48 h after dosing. BLZ-100 was well tolerated. There were no serious adverse events, deaths, or discontinuations due to adverse events, and no maximum tolerated dose (MTD) was identified. Headache (n = 2) and nausea (n = 2) were the only BLZ-100 treatment-related adverse events reported for >1 patient. Median time to maximal serum concentration was <0.5 h. Exposure based on maximal serum concentrations increased in a greater than dose-proportional manner. For intermediate dose-levels (3-12 mg), 4 of 5 basal cell carcinomas and 4 of 4 melanomas were considered positive for BLZ-100 fluorescence. BLZ-100 was well tolerated at all dose levels tested and these results support further clinical testing of this imaging agent in surgical oncology settings. Clinicaltrials.gov: NCT02097875.
Language	English
Publishing date	2021-08-04
Publishing country	Netherlands
Document type	Journal Article
ISSN	2451-8654
ISSN (online)	2451-8654
DOI	10.1016/j.conctc.2021.100830
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure.

Cook Sangar, Michelle L / Girard, Emily J / Hopping, Gene / Yin, Chunfeng / Pakiam, Fiona / Brusniak, Mi-Youn / Nguyen, Elizabeth / Ruff, Raymond / Gewe, Mesfin M / Byrnes-Blake, Kelly / Nairn, Natalie W / Miller, Dennis M / Mehlin, Christopher / Strand, Andrew D / Mhyre, Andrew J / Correnti, Colin E / Strong, Roland K / Simon, Julian A / Olson, James M

Science translational medicine

2020 Volume 12, Issue 533

Abstract: On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense ... ...

Abstract	On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense peptides (CDPs) that rapidly accumulate in cartilage of the knees, ankles, hips, shoulders, and intervertebral discs after systemic administration. These CDPs could be used to concentrate arthritis drugs in joints. A cartilage-accumulating peptide, CDP-11R, reached peak concentration in cartilage within 30 min after administration and remained detectable for more than 4 days. Structural analysis of the peptides by crystallography revealed that the distribution of positive charge may be a distinguishing feature of joint-accumulating CDPs. In addition, quantitative whole-body autoradiography showed that the disulfide-bonded tertiary structure is critical for cartilage accumulation and retention. CDP-11R distributed to joints while carrying a fluorophore imaging agent or one of two different steroid payloads, dexamethasone (dex) and triamcinolone acetonide (TAA). Of the two payloads, the dex conjugate did not advance because the free drug released into circulation was sufficient to cause on-target toxicity. In contrast, the CDP-11R-TAA conjugate alleviated joint inflammation in the rat collagen-induced model of rheumatoid arthritis while avoiding toxicities that occurred with nontargeted steroid treatment at the same molar dose. This conjugate shows promise for clinical development and establishes proof of concept for multijoint targeting of disease-modifying therapeutic payloads.
MeSH term(s)	Adrenal Cortex Hormones ; Animals ; Arthritis, Experimental/drug therapy ; Cartilage ; Humans ; Peptides ; Rats ; Steroids
Chemical Substances	Adrenal Cortex Hormones ; Peptides ; Steroids
Language	English
Publishing date	2020-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aay1041
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6941: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phase 1 Safety, Pharmacokinetics, and Fluorescence Imaging Study of Tozuleristide (BLZ-100) in Adults With Newly Diagnosed or Recurrent Gliomas.

Patil, Chirag G / Walker, David G / Miller, Dennis M / Butte, Pramod / Morrison, Beth / Kittle, David S / Hansen, Stacey J / Nufer, Kaitlin L / Byrnes-Blake, Kelly A / Yamada, Miko / Lin, Lynlee L / Pham, Kim / Perry, Jeff / Parrish-Novak, Julia / Ishak, Laura / Prow, Tarl / Black, Keith / Mamelak, Adam N

Neurosurgery

2019 Volume 85, Issue 4, Page(s) E641–E649

Abstract: Background: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate ... ...

Abstract	Background: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types. Objective: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. Methods: Patients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures. Results: A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with high-grade tumors generally showing greater fluorescence intensity compared to lower grade tumors. In high-grade tumors, signal intensity increased with increased dose levels of tozuleristide, regardless of the time of dosing relative to surgery. Conclusion: These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.
MeSH term(s)	Adult ; Aged ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/metabolism ; Brain Neoplasms/surgery ; Dose-Response Relationship, Drug ; Female ; Fluorescent Dyes/administration & dosage ; Fluorescent Dyes/pharmacokinetics ; Glioma/diagnostic imaging ; Glioma/metabolism ; Glioma/surgery ; Humans ; Indocyanine Green/administration & dosage ; Indocyanine Green/analogs & derivatives ; Indocyanine Green/pharmacokinetics ; Injections, Intravenous ; Male ; Middle Aged ; Neoplasm Recurrence, Local/diagnostic imaging ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/surgery ; Optical Imaging/methods ; Scorpion Venoms/administration & dosage ; Scorpion Venoms/pharmacokinetics
Chemical Substances	Fluorescent Dyes ; Scorpion Venoms ; tozuleristide (835UH424TU) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2019-05-08
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	135446-2
ISSN	1524-4040 ; 0148-396X
ISSN (online)	1524-4040
ISSN	0148-396X
DOI	10.1093/neuros/nyz125
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1424: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 539: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Pharmacokinetics and pharmacodynamics of pegylated interferon lambda-1 in cynomolgus monkeys.

Byrnes-Blake, Kelly A / Pederson, Susan / Klucher, Kevin M / Anderson-Haley, Monica / Miller, Dennis M / Lopez-Talavera, Juan Carlos / Freeman, Jeremy A

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2012 Volume 32, Issue 5, Page(s) 198–206

Abstract: Type III lambda interferons (IFNs) have activity similar to type I IFNs, but a more restricted receptor distribution. A pegylated human IFN lambda-1 (pegIFNλ) is under development for chronic hepatitis C. Induction of receptor signaling (STAT1 ... ...

Abstract	Type III lambda interferons (IFNs) have activity similar to type I IFNs, but a more restricted receptor distribution. A pegylated human IFN lambda-1 (pegIFNλ) is under development for chronic hepatitis C. Induction of receptor signaling (STAT1 phosphorylation) and expression of interferon-stimulated genes (ISGs) by pegIFNλ were assessed in, respectively, cynomolgus monkey leukocyte subsets and hepatocytes stimulated in vitro. ISG induction by pegIFNλ or IFNα was also assessed in peripheral leukocytes and liver biopsies after single and repeat (x3) dosing of pegIFNλ (0.03, 0.3, 3.0 mg/kg) or unpegylated IFNα-2b (10(7) IU/kg). Single-dose pharmacokinetics of pegIFNλ were evaluated. Strong ISG induction occurred in cultured hepatocytes and liver biopsies with both pegIFNλ and IFNα. However, STAT1 phosphorylation, MHC class 1 upregulation, and ISG induction in leukocytes only occurred with IFNα. Serum neopterin was unaffected by pegIFNλ; however, β-2-microglobulin was elevated at all doses. The terminal half-life of pegIFNλ was 23 h with a 59 mL/kg volume of distribution, consistent with other pegylated IFNs. Serum exposure was dose-proportional across the dosing range. These data demonstrate the suitability of cynomolgus monkeys for the preclinical evaluation of pegIFNλ. Additionally, the absence of pegIFNλ pharmacologic activity in leukocytes is consistent with its low receptor expression in blood.
MeSH term(s)	Animals ; Cells, Cultured ; Drug Evaluation, Preclinical ; Gene Expression Regulation ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/immunology ; Hepatocytes/drug effects ; Hepatocytes/immunology ; Humans ; Immunotherapy ; Interferons ; Interleukins/administration & dosage ; Interleukins/chemistry ; Interleukins/pharmacokinetics ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Macaca fascicularis ; Phosphorylation/drug effects ; Polyethylene Glycols/chemistry ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; Signal Transduction/drug effects
Chemical Substances	interferon-lambda, human ; Interleukins ; STAT1 Transcription Factor ; Polyethylene Glycols (3WJQ0SDW1A) ; Interferons (9008-11-1)
Language	English
Publishing date	2012-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2011.0075
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1748: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Preclinical safety, pharmacokinetics, and pharmacodynamics of recombinant human interleukin-21 in cynomolgus macaques (Macaca fascicularis).

Waggie, Kimberly S / Holdren, Matthew S / Byrnes-Blake, Kelly / Pedersen, Susan / Ponce, Rafael / Hughes, Steven / Miller, Dennis M

International journal of toxicology

2012 Volume 31, Issue 4, Page(s) 303–316

Abstract: Interleukin-21 (IL-21), a pleiotropic immunostimulatory type I cytokine, has anticancer effects in animal models. Preclinical studies designed to assess the safety of recombinant human IL-21 (rIL-21) for use in phase I oncology studies are described. The ...

Abstract	Interleukin-21 (IL-21), a pleiotropic immunostimulatory type I cytokine, has anticancer effects in animal models. Preclinical studies designed to assess the safety of recombinant human IL-21 (rIL-21) for use in phase I oncology studies are described. The rIL-21 (≤3.0 mg/kg per dose) was given intravenously to cynomolgus monkeys (Macaca fascicularis) once daily for 5 days, followed by 9 nondosing days (1 cycle) for ≤4 cycles. The rIL-21 pharmacokinetics was dose-dependent. Accumulation was not observed after repeated dosing, consistent with the short elimination half-life (t (1/2,λz); 0.4-0.8 hours). Safety findings included cyclical anemia and thrombocytopenia, clinical pathology changes consistent with acute-phase response, leukocyte infiltrates in hepatic sinusoids, and sporadic serum transaminase elevations (typically <3 times upper-limit of normal); all were reversible upon cessation of treatment. Decreased pharmacodynamic responses with time corresponded to the development of anti-rIL-21 antibodies; effects varied among individuals and were dose-dependent. These studies demonstrated rIL-21 to be generally well-tolerated when administered to cynomolgus monkeys, and all adverse effects were reversible upon treatment cessation. However, development of anti-rIL-21 antibodies may limit the use of this species in long-term studies.
MeSH term(s)	Acute-Phase Reaction/drug therapy ; Animals ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Female ; Half-Life ; Humans ; Interleukins/blood ; Interleukins/pharmacokinetics ; Interleukins/pharmacology ; Macaca fascicularis ; Male ; Phosphorylation ; Recombinant Proteins/pharmacokinetics ; Recombinant Proteins/pharmacology ; STAT3 Transcription Factor/metabolism
Chemical Substances	Interleukins ; Recombinant Proteins ; STAT3 Transcription Factor ; interleukin-21
Language	English
Publishing date	2012-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1379845-5
ISSN	1092-874X ; 1091-5818
ISSN (online)	1092-874X
ISSN	1091-5818
DOI	10.1177/1091581812449661
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1870: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

Parrish-Novak, Julia / Byrnes-Blake, Kelly / Lalayeva, Narine / Burleson, Stefanie / Fidel, Janean / Gilmore, Rhonda / Gayheart-Walsten, Pamela / Bricker, Gregory A / Crumb, William J / Tarlo, K S / Hansen, Stacey / Wiss, Valorie / Malta, Errol / Dernell, William S / Olson, James M / Miller, Dennis M

International journal of toxicology

2017 Volume 36, Issue 2, Page(s) 104–112

Abstract: BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. ... ...

Abstract	BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.
MeSH term(s)	Animals ; Complement System Proteins/analysis ; Dogs ; Drug Hypersensitivity/blood ; Female ; Fluorescent Dyes/pharmacokinetics ; Fluorescent Dyes/toxicity ; HEK293 Cells ; Histamine/blood ; Humans ; Indocyanine Green/analogs & derivatives ; Indocyanine Green/pharmacokinetics ; Indocyanine Green/toxicity ; Macaca fascicularis ; Male ; Mice ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Rats, Sprague-Dawley ; Scorpion Venoms/blood ; Scorpion Venoms/pharmacokinetics ; Scorpion Venoms/toxicity
Chemical Substances	Fluorescent Dyes ; Scorpion Venoms ; Histamine (820484N8I3) ; tozuleristide (835UH424TU) ; Complement System Proteins (9007-36-7) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2017-03-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1379845-5
ISSN	1092-874X ; 1091-5818
ISSN (online)	1092-874X
ISSN	1091-5818
DOI	10.1177/1091581817697685
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1870: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Monoclonal IgG affinity and treatment time alters antagonism of (+)-methamphetamine effects in rats.

Byrnes-Blake, Kelly A / Laurenzana, Elizabeth M / Landes, Reid D / Gentry, W Brooks / Owens, S Michael

European journal of pharmacology

2005 Volume 521, Issue 1-3, Page(s) 86–94

Abstract: The roles of monoclonal antibody affinity and treatment time of (+)-methamphetamine-induced pharmacological effects in rats were studied using two anti-(+)-methamphetamine monoclonal antibodies. These studies tested the preclinical protective effects of ... ...

Abstract	The roles of monoclonal antibody affinity and treatment time of (+)-methamphetamine-induced pharmacological effects in rats were studied using two anti-(+)-methamphetamine monoclonal antibodies. These studies tested the preclinical protective effects of monoclonal antibody antagonists in (+)-methamphetamine overdose and pretreatment scenarios. The higher affinity antibody (mAb6H4; KD=11 nM for (+)-methamphetamine) more effectively antagonized (+)-methamphetamine-induced behavioral effects (distance and rearing) than the low affinity antibody (designated mAb6H8; KD=250 nM) and had a longer duration of action. Both antibodies more effectively reduced (+)-methamphetamine effects in the overdose model than in the pretreatment model. (+)-Methamphetamine pharmacokinetic studies showed the mAb6H4 significantly reduced brain concentrations over time in both models. However, while mAb6H4 immediately reduced brain concentrations in the overdose model, it did not prevent the initial distribution of (+)-methamphetamine into the brain in the pretreatment model. Thus, anti-(+)-methamphetamine monoclonal antibody affinity and administration time (relative to (+)-methamphetamine dosing) are critical determinants of therapeutic success.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibody Affinity/immunology ; Antibody Specificity/immunology ; Behavior, Animal/drug effects ; Central Nervous System Stimulants/toxicity ; Disease Models, Animal ; Drug Overdose/drug therapy ; Drug Overdose/prevention & control ; Female ; Immunoglobulin G/immunology ; Immunoglobulin G/pharmacology ; Male ; Methamphetamine/immunology ; Methamphetamine/toxicity ; Mice ; Mice, Inbred BALB C ; Motor Activity/drug effects ; Rats ; Rats, Sprague-Dawley ; Time Factors
Chemical Substances	Antibodies, Monoclonal ; Central Nervous System Stimulants ; Immunoglobulin G ; Methamphetamine (44RAL3456C)
Language	English
Publishing date	2005-10-03
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2005.08.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 522: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study.

Bhatia, Shailender / Curti, Brendan / Ernstoff, Marc S / Gordon, Michael / Heath, Elisabeth I / Miller, Wilson H / Puzanov, Igor / Quinn, David I / Flaig, Thomas W / VanVeldhuizen, Peter / Byrnes-Blake, Kelly / Freeman, Jeremy A / Bittner, Rachel / Hunder, Naomi / Souza, Sonia / Thompson, John A

Journal for immunotherapy of cancer

2014 Volume 2, Page(s) 2

Abstract: Background: Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of ...

Abstract	Background: Despite the positive impact of targeted therapies on metastatic renal cell carcinoma (mRCC), durable responses are infrequent and an unmet need exists for novel therapies with distinct mechanisms of action. We investigated the combination of recombinant Interleukin 21 (IL-21), a cytokine with unique immunostimulatory properties, plus sorafenib, a VEGFR tyrosine kinase inhibitor. Methods: In this phase 1/2 study, 52 mRCC patients received outpatient treatment with oral sorafenib 400 mg twice daily plus intravenous IL-21 (10-50 mcg/kg) on days 1-5 and 15-19 of each 7-week treatment course. The safety, antitumor activity, pharmacokinetic and pharmacodynamic effects of the combination were evaluated. Results: In phase 1 (n = 19), the maximum tolerated dose for IL-21 with the standard dose of sorafenib was determined to be 30 mcg/kg/day; grade 3 skin rash was the only dose-limiting toxicity. In phase 2, 33 previously-treated patients tolerated the combination therapy well with appropriate dose reductions; toxicities were mostly grade 1 or 2. The objective response rate was 21% and disease control rate was 82%. Two patients have durable responses that are ongoing, despite cessation of both IL-21 and sorafenib, at 41+ and 30+ months, respectively. The median progression-free survival in phase 2 was 5.6 months. The pharmacokinetic and pharmacodynamic properties of IL-21 appeared to be preserved in the presence of sorafenib. Conclusion: IL-21 plus sorafenib has antitumor activity and acceptable safety in previously treated mRCC patients. IL-21 may represent a suitable immunotherapy in further exploration of combination strategies in mRCC. Trial registration: ClinicalTrials.gov Identifier: NCT00389285.
Language	English
Publishing date	2014-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426
ISSN	2051-1426
DOI	10.1186/2051-1426-2-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats.

Milesi-Hallé, Alessandra / McMillan, Donald E / Laurenzana, Elizabeth M / Byrnes-Blake, Kelly A / Owens, S Michael

Pharmacology, biochemistry, and behavior

2007 Volume 86, Issue 1, Page(s) 140–149

Abstract: Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, ... ...

Abstract	(+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics.
MeSH term(s)	Amphetamine/pharmacology ; Animals ; Behavior, Animal/drug effects ; Central Nervous System Stimulants/pharmacology ; Female ; Injections, Intravenous ; Male ; Methamphetamine/pharmacology ; Motor Activity/drug effects ; Rats ; Rats, Sprague-Dawley ; Sex Characteristics ; Stereotyped Behavior/drug effects ; Substance-Related Disorders
Chemical Substances	Central Nervous System Stimulants ; Methamphetamine (44RAL3456C) ; Amphetamine (CK833KGX7E)
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2006.12.018
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.A 1060: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Recombinant soluble human FcgammaR1A (CD64A) reduces inflammation in murine collagen-induced arthritis.

Ellsworth, Jeff L / Hamacher, Nels / Harder, Brandon / Bannink, Ken / Bukowski, Thomas R / Byrnes-Blake, Kelly / Underwood, Sara / Oliver, Colleen / Waggie, Kimberly S / Noriega, Claire / Hebb, LuAnne / Rixon, Mark W / Lewis, Katherine E

Journal of immunology (Baltimore, Md. : 1950)

2009 Volume 182, Issue 11, Page(s) 7272–7279

Abstract: Binding of immune complexes to cellular FcgammaRs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble FcgammaR, rh-FcgammaRIA (CD64A), was shown to block inflammation in passive transfer models of immune ... ...

Abstract	Binding of immune complexes to cellular FcgammaRs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble FcgammaR, rh-FcgammaRIA (CD64A), was shown to block inflammation in passive transfer models of immune complex-mediated disease. To assess whether rh-FcgammaRIA could block inflammation in a T cell- and B cell-dependent model of immune complex-mediated disease, the efficacy of rh-FcgammaRIA in collagen-induced arthritis was evaluated. Mice with established arthritis were treated with a single s.c. injection of rh-FcgammaRIA (0.2-2.0 mg/dose) given every other day for 11 days. Relative to mice injected with vehicle alone, mice treated with rh-FcgammaRIA exhibited lower serum concentrations of IL-6, anti-type II collagen Abs, and total IgG2a. These changes were correlated with lower levels of paw swelling and joint damage in the rh-FcgammaRIA-treated mice and occurred in the presence of a significant murine Ab response to rh-FcgammaRIA. Comparison of the serum rh-FcgammaRIA concentration vs time profiles for rh-FcgammaRIA administered at two dose levels by i.v. and s.c. injection revealed that the bioavailabilty of s.c. administered rh-FcgammaRIA was 27-37%. Taken together, these data show that rh-FcgammaRIA is an effective inhibitor of inflammation in a model of established arthritis in mice.
MeSH term(s)	Animals ; Antibodies/blood ; Antibody Formation ; Arthritis/chemically induced ; Arthritis/drug therapy ; Arthritis/pathology ; Collagen/adverse effects ; Collagen/immunology ; Humans ; Immunoglobulin G/blood ; Inflammation/drug therapy ; Interleukin-6/blood ; Mice ; Pharmacokinetics ; Receptors, IgG/administration & dosage ; Receptors, IgG/therapeutic use ; Recombinant Proteins ; Solubility ; Treatment Outcome
Chemical Substances	Antibodies ; Fcgr1 protein, mouse ; Immunoglobulin G ; Interleukin-6 ; Receptors, IgG ; Recombinant Proteins ; Collagen (9007-34-5)
Language	English
Publishing date	2009-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.0803497
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito