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Article ; Online: In vivo bio-imaging using chlorotoxin-based conjugates.

Stroud, Mark R / Hansen, Stacey J / Olson, James M

2011 Volume 17, Issue 38, Page(s) 4362–4371

Abstract: Surgical resection remains the primary component of cancer therapy. The precision required to successfully separate cancer tissue from normal tissue relies heavily on the surgeon's ability to delineate the tumor margins. Despite recent advances in ... ...

Abstract	Surgical resection remains the primary component of cancer therapy. The precision required to successfully separate cancer tissue from normal tissue relies heavily on the surgeon's ability to delineate the tumor margins. Despite recent advances in surgical guidance and monitoring systems, intra-operative identification of these margins remains imprecise and directly influences patient prognosis. If the surgeon had improved tools to distinguish these margins, tumor progression and unacceptable morbidity could be avoided. In this article, we review the history of chlorotoxin and its tumor specificity and discuss the research currently being generated to target optical imaging agents to cancer tissue.
MeSH term(s)	Amino Acid Sequence ; Animals ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Brain Neoplasms/surgery ; Contrast Media/chemistry ; Contrast Media/pharmacokinetics ; Diagnostic Imaging/instrumentation ; Diagnostic Imaging/methods ; Fluorescent Dyes/chemistry ; Humans ; Intraoperative Care/instrumentation ; Intraoperative Care/methods ; Models, Molecular ; Molecular Sequence Data ; Nanoparticles ; Protein Binding ; Scorpion Venoms/chemistry ; Scorpion Venoms/isolation & purification ; Scorpion Venoms/pharmacokinetics ; Spectrometry, Fluorescence
Chemical Substances	Contrast Media ; Fluorescent Dyes ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57)
Language	English
Publishing date	2011-12-28
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/138161211798999375
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Zs.A 4714: Show issues

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Article ; Online: Transcriptional inhibition of REST by NeuroD2 during neuronal differentiation.

Ravanpay, Ali C / Hansen, Stacey J / Olson, James M

Molecular and cellular neurosciences

2010 Volume 44, Issue 2, Page(s) 178–189

Abstract: For a progenitor cell to become a neuron, three activities must occur: neuronal differentiation program must be activated, elements repressing neuronal differentiation must be deactivated and competing differentiation programs must be silenced. It is ... ...

Abstract	For a progenitor cell to become a neuron, three activities must occur: neuronal differentiation program must be activated, elements repressing neuronal differentiation must be deactivated and competing differentiation programs must be silenced. It is known that NeuroD2 and related bHLH transcription factors induce neuronal differentiation, REST represses neuronal differentiation, and Zfhx1a prevents myogenic gene expression. We demonstrate that NeuroD2 suppresses REST during differentiation in culture. In the hippocampus of NeuroD2 knockout mice, higher level of REST is detected. Functional significance of NeuroD2-REST interplay is uncovered by showing that forced expression of REST interferes with neuronal differentiation in culture. NeuroD2 inhibits REST indirectly by involving the inhibitor of myogenic genes, Zfhx1a, which binds response elements in REST 5'-UTR. Our study supports a model wherein NeuroD2 induces transcription of neuronal genes and Zfhx1a, which in turn de-represses neuronal differentiation by down-regulating REST, and suppresses competing myogenic fate.
MeSH term(s)	5' Untranslated Regions/genetics ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Brain/cytology ; Brain/growth & development ; Brain/metabolism ; Cell Differentiation/physiology ; Cell Line, Tumor ; Down-Regulation/genetics ; Embryonal Carcinoma Stem Cells ; Gene Expression Regulation, Developmental/physiology ; Hippocampus/cytology ; Hippocampus/growth & development ; Hippocampus/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Mice ; Mice, Knockout ; Neurogenesis/physiology ; Neurons/cytology ; Neurons/metabolism ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Response Elements/genetics ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Activation/physiology
Chemical Substances	5' Untranslated Regions ; Basic Helix-Loop-Helix Transcription Factors ; Homeodomain Proteins ; Neurod2 protein, mouse ; Neuropeptides ; RE1-silencing transcription factor ; Repressor Proteins ; Transcription Factors ; Zfhx1a protein, mouse
Language	English
Publishing date	2010-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1046640-x
ISSN	1095-9327 ; 1044-7431
ISSN (online)	1095-9327
ISSN	1044-7431
DOI	10.1016/j.mcn.2010.03.006
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Zs.A 3035: Show issues

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Article ; Online: Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide.

Dintzis, Suzanne M / Hansen, Stacey / Harrington, Kristi M / Tan, Lennart C / Miller, Dennis M / Ishak, Laura / Parrish-Novak, Julia / Kittle, David / Perry, Jeff / Gombotz, Carolyn / Fortney, Tina / Porenta, Stephanie / Hales, Lisa / Calhoun, Kristine E / Anderson, Benjamin O / Javid, Sara H / Byrd, David R

Archives of pathology & laboratory medicine

2018 Volume 143, Issue 9, Page(s) 1076–1083

Abstract: Context.—: Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin ... ...

Abstract	Context.—: Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment. In this study, fluorescence imaging was conducted ex vivo on gross breast pathology specimens. Objectives.—: To determine the potential of tozuleristide to detect breast carcinoma in fresh pathology specimens and the feasibility of fluorescence-guided intraoperative pathology assessment of surgical margins. Design.—: Twenty-three patients received an intravenous bolus dose of 6 or 12 mg of tozuleristide at least 1 hour before surgery. Fifteen lumpectomy and 12 mastectomy specimens were evaluated for fluorescence by the site's clinical pathology staff using the SIRIS, an investigational near-infrared imaging device. The breast tissue was then processed per usual procedures. Fluorescent patterns were correlated with the corresponding hematoxylin-eosin-stained sections. Clinical pathology reports were used to correlate fluorescent signal to grade, histotype, prognostic marker status, and margin measurements. Results.—: Tozuleristide fluorescence was readily observed in invasive and in situ breast carcinoma specimens. Most invasive carcinomas were bright and focal, whereas in situ lesions demonstrated a less intense, more diffuse pattern. Tozuleristide was detected in ductal and lobular carcinomas with a similar fluorescent pattern. Fluorescence was detected in high- and low-grade lesions, and molecular marker/hormone receptor status did not affect signal. Fluorescence could be used to identify the relationship of carcinoma to margins intraoperatively. Conclusions.—: Tumor targeting with tozuleristide allowed visual real-time distinction between pathologically confirmed breast carcinoma and normal tissue.
MeSH term(s)	Breast Carcinoma In Situ/diagnostic imaging ; Breast Carcinoma In Situ/pathology ; Breast Carcinoma In Situ/surgery ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/surgery ; Carcinoma, Ductal, Breast/diagnostic imaging ; Carcinoma, Ductal, Breast/pathology ; Carcinoma, Ductal, Breast/surgery ; Carcinoma, Lobular/diagnostic imaging ; Carcinoma, Lobular/pathology ; Carcinoma, Lobular/surgery ; Female ; Fluorescent Dyes ; Humans ; Indocyanine Green/analogs & derivatives ; Intraoperative Care/methods ; Margins of Excision ; Mastectomy ; Mastectomy, Segmental ; Neoplasm Invasiveness/diagnostic imaging ; Neoplasm Invasiveness/pathology ; Prognosis ; Scorpion Venoms
Chemical Substances	Fluorescent Dyes ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57) ; tozuleristide (835UH424TU) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2018-12-14
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2018-0197-OA
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Article ; Online: Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate.

Baik, Fred M / Hansen, Stacey / Knoblaugh, Sue E / Sahetya, Disha / Mitchell, Ryan M / Xu, Chang / Olson, James M / Parrish-Novak, Julia / Méndez, Eduardo

JAMA otolaryngology-- head & neck surgery

2016 Volume 142, Issue 4, Page(s) 330–338

Abstract: Importance: Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet ... ...

Abstract	Importance: Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC. Objective: To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. Design, setting, and participants: This was an observational study (including sensitivity and specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches. Interventions: Various HNSCC xenografts were established in the tongues of NOD-scid IL2Rgammanull (NSG) mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the cheek pouch of Golden Syrian hamsters for 9 to16 weeks. BLZ-100 was subcutaneously injected, and fluorescence uptake was measured. Main outcomes and measures: The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades. Results: In HNSCC xenografts, BLZ-100 demonstrated a mean (SD) SBR of 2.51 (0.47). The ROC curve demonstrated an area under the curve (AUC) of 0.89; an SBR of 2.50 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and nontumor interface, the AUC increased to 0.97; an SBR of 2.50 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 [0.71] vs 1.51 [0.34], P = .006). Conclusions and relevance: BLZ-100 is a sensitive and specific marker of HNSCC and can distinguish high-risk from low-risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of premalignant lesions.
MeSH term(s)	Animals ; Carcinoma, Squamous Cell/diagnosis ; Carcinoma, Squamous Cell/metabolism ; Cell Line, Tumor ; Coloring Agents/pharmacology ; Cricetinae ; Head and Neck Neoplasms/diagnosis ; Head and Neck Neoplasms/metabolism ; Heterografts ; Humans ; Image Processing, Computer-Assisted ; Indocyanine Green/analogs & derivatives ; Indocyanine Green/pharmacokinetics ; Iodine Radioisotopes ; Mesocricetus ; Mice ; Mice, Inbred NOD ; Mouth Neoplasms/diagnosis ; Mouth Neoplasms/metabolism ; Neoplasms, Experimental ; ROC Curve ; Scorpion Venoms/pharmacokinetics ; Scorpion Venoms/pharmacology ; Squamous Cell Carcinoma of Head and Neck ; Tongue/pathology
Chemical Substances	Coloring Agents ; Iodine Radioisotopes ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57) ; tozuleristide (835UH424TU) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2016-02-12
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701825-8
ISSN	2168-619X ; 2168-6181
ISSN (online)	2168-619X
ISSN	2168-6181
DOI	10.1001/jamaoto.2015.3617
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Ul II Zs.87: Show issues

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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
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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

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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
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Article ; Online: Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy.

Akcan, Muharrem / Stroud, Mark R / Hansen, Stacey J / Clark, Richard J / Daly, Norelle L / Craik, David J / Olson, James M

Journal of medicinal chemistry

2011 Volume 54, Issue 3, Page(s) 782–787

Abstract: Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the ... ...

Abstract	Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and trilabeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either alanine or arginine, which resulted in only monolabeled peptide that was functionally equivalent to native chlorotoxin/Cy5.5. We also analyzed the serum stability and serum half-life of cyclized chlorotoxin, which showed an 11 h serum half-life and resulted in a monolabeled product. Based on these data, we propose to advance a monolabeled chlorotoxin to human clinical trials.
MeSH term(s)	Alanine/chemistry ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Arginine/chemistry ; Brain Neoplasms/diagnosis ; Brain Neoplasms/therapy ; Carbocyanines/chemistry ; Fluorescent Dyes/chemistry ; Half-Life ; Lysine/chemistry ; Medulloblastoma/diagnosis ; Medulloblastoma/therapy ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Molecular Sequence Data ; Peptides/blood ; Peptides/chemistry ; Peptides, Cyclic/blood ; Peptides, Cyclic/chemistry ; Scorpion Venoms/blood ; Scorpion Venoms/chemistry
Chemical Substances	CY5.5 cyanine dye ; Carbocyanines ; Fluorescent Dyes ; Peptides ; Peptides, Cyclic ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57) ; Arginine (94ZLA3W45F) ; Lysine (K3Z4F929H6) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2011-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/jm101018r
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Zs.B 151: 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)
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Article ; Online: Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.

Fidel, Janean / Kennedy, Katie C / Dernell, William S / Hansen, Stacey / Wiss, Valorie / Stroud, Mark R / Molho, Joshua I / Knoblaugh, Sue E / Meganck, Jeffrey / Olson, James M / Rice, Brad / Parrish-Novak, Julia

Cancer research

2014 Volume 75, Issue 20, Page(s) 4283–4291

Abstract: There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide- ... ...

Abstract	There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.
MeSH term(s)	Adolescent ; Animals ; Child ; Child, Preschool ; Contrast Media/administration & dosage ; Diagnostic Imaging/instrumentation ; Diagnostic Imaging/methods ; Disease Models, Animal ; Dogs ; Female ; Fluorescent Dyes/administration & dosage ; Humans ; Indocyanine Green/administration & dosage ; Indocyanine Green/analogs & derivatives ; Intraoperative Care ; Male ; Neoplasms/diagnosis ; Neoplasms/pathology ; Reproducibility of Results ; Scorpion Venoms/administration & dosage
Chemical Substances	Contrast Media ; Fluorescent Dyes ; Scorpion Venoms ; tozuleristide (835UH424TU) ; Indocyanine Green (IX6J1063HV)
Language	English
Publishing date	2014-08-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-15-0471
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Article: The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning.

Lin, Chin-Hsing / Hansen, Stacey / Wang, Zhenshan / Storm, Daniel R / Tapscott, Stephen J / Olson, James M

Proceedings of the National Academy of Sciences of the United States of America

2005 Volume 102, Issue 41, Page(s) 14877–14882

Abstract: The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this ...

Abstract	The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators of emotional learning were diminished in the brains of neuroD2 heterozygotes including Ulip1, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and GABA(A) receptor. Thus, neuroD2 is essential for amygdala development and genes involved in amygdala function are altered in neuroD2-deficient mice.
MeSH term(s)	Amygdala/growth & development ; Amygdala/metabolism ; Animals ; Apoptosis/physiology ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Behavioral Symptoms ; Blotting, Western ; Chromatin Immunoprecipitation ; Emotions/physiology ; Heterozygote ; Immunohistochemistry ; In Situ Nick-End Labeling ; Learning/physiology ; Mice ; Nerve Tissue Proteins/metabolism ; Neuropeptides/genetics ; Neuropeptides/metabolism
Chemical Substances	Basic Helix-Loop-Helix Transcription Factors ; Nerve Tissue Proteins ; Neurod2 protein, mouse ; Neuropeptides
Language	English
Publishing date	2005-10-11
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0506785102
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Article ; Online: Tumor-targeted drug delivery and MRI contrast enhancement by chlorotoxin-conjugated iron oxide nanoparticles.

Sun, Conroy / Fang, Chen / Stephen, Zachary / Veiseh, Omid / Hansen, Stacey / Lee, Donghoon / Ellenbogen, Richard G / Olson, Jim / Zhang, Miqin

Nanomedicine (London, England)

2007 Volume 3, Issue 4, Page(s) 495–505

Abstract: Aims: This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells.: Materials & methods: Iron oxide nanoparticles were synthesized and ... ...

Abstract	Aims: This study examines the capabilities of an actively targeting superparamagnetic nanoparticle to specifically deliver therapeutic and MRI contrast agents to cancer cells. Materials & methods: Iron oxide nanoparticles were synthesized and conjugated to both a chemotherapeutic agent, methotrexate, and a targeting ligand, chlorotoxin, through a poly(ethylene glycol) linker. Cytotoxicity of this nanoparticle conjugate was evaluated by Alamar Blue cell viability assays, while tumor-cell specificity was examined in vitro and in vivo by MRI. Results & discussion: Characterization of these multifunctional nanoparticles confirms the successful attachment of both drug and targeting ligands. The targeting nanoparticle demonstrated preferential accumulation and increased cytotoxicity in tumor cells. Furthermore, prolonged retention of these nanoparticles was observed within tumors in vivo. Conclusion: The improved specificity, extended particle retention and increased cytotoxicity toward tumor cells demonstrated by this multifunctional nanoparticle system suggest that it possesses potential for applications in cancer diagnosis and treatment.
MeSH term(s)	Animals ; Antimetabolites, Antineoplastic/administration & dosage ; Antimetabolites, Antineoplastic/chemistry ; Antimetabolites, Antineoplastic/therapeutic use ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects ; Contrast Media/administration & dosage ; Contrast Media/chemistry ; Drug Delivery Systems/methods ; Ferric Compounds/chemistry ; Humans ; Image Enhancement ; Magnetic Resonance Imaging/methods ; Methotrexate/administration & dosage ; Methotrexate/chemistry ; Methotrexate/therapeutic use ; Mice ; Microscopy, Electron ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Nanoparticles/ultrastructure ; Neoplasms/drug therapy ; Neoplasms/pathology ; Scorpion Venoms/chemistry ; Spectroscopy, Fourier Transform Infrared ; Xenograft Model Antitumor Assays
Chemical Substances	Antimetabolites, Antineoplastic ; Contrast Media ; Ferric Compounds ; Scorpion Venoms ; Chlorotoxin (06UV5RFW57) ; ferric oxide (1K09F3G675) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2007-10-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2277839-1
ISSN	1748-6963 ; 1743-5889
ISSN (online)	1748-6963
ISSN	1743-5889
DOI	10.2217/17435889.3.4.495
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