Biomedical subjects

Martin Funovics

Publications and source records attributed to Martin Funovics.

9 recordsLinked to original sources

PubMed2006

Multivalent effects of RGD peptides obtained by nanoparticle display.

The binding of RGD peptides to integrins offers an excellent system to study the multivalent mediated changes in affinity that arise when peptides, displayed on the surface of a nanoparticle carrier, bind to integrins displayed on the cell membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with strong multivalent effects, defined as a multivalent enhancement factor (MVE) of 38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The attachment of RGD peptides to nanoparticles resulted in an extension of the peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized materials should be potent inhibitors of the alpha(V)beta(3) function on endothelial cells in vivo.

Animals↗

PubMed2005

A novel mouse model for segmental orthotopic colon cancer.

Spontaneous colon tumor mouse strains offer numerous advantages in modeling disease. However, the wide temporal window in which lesions form and the stochastic nature of lesion location require larger cohorts for assessment of disease modulation. Reliable, reproducible and inexpensive mouse models of early-stage and invasive cancer would add to existing transgenic models. We show a new method for the creation of orthotopic murine tumors centered in the mucosal and submucosal layers anywhere in the colon, allowing creation of lesions of known age, location and extent. The system overcomes the disadvantages of heterotopic implantation and allows evaluation of lesions distally in the colon as well as proximally, thereby providing an additional method to study the effects of regionality. Invasion, host vascularization and application to disparate cell lines are demonstrated. Noninvasive imaging with magnetic resonance and colonoscopy, allowed in part by the tumor location, show potential applications of this approach.

Animals↗

PubMed2005

Nanoparticles for the optical imaging of tumor E-selectin.

We designed a fluorescent peptide-magnetic nanoparticle conjugate that images E-selectin expression in mouse xenograft models of Lewis lung carcinoma (LLC) by fluorescence reflectance imaging. It was synthesized by attaching the E-selectin-binding peptide (ESBP; CDSDSDITWDQLWDLMK) to a CLIO(Cy5.5) nanoparticle to yield ESBP-CLIO(Cy5.5). Internalization by activated human umbilical vein endothelial cells (HUVECs) was rapid and mediated by E-selectin, indicated by the lack of uptake of nanoparticles bearing similar numbers of a scrambled peptide (Scram). To demonstrate the specificity of E-selectin targeting to ESBP-CLIO(Cy5.5) in vivo, we coinjected ESBP-CLIO(Cy5.5) and Scram-CLIO(Cy3.5) and demonstrated a high Cy5.5/Cy3.5 fluorescence ratio using the LLC. Histology showed that ESBP-CLIO was associated with tumor cells as well as endothelial cells, but fluorescence-activated cell sorter analysis showed a far less expression of E-selectin on LLC than on HUVECs. Using immunohistochemistry, we demonstrated E-selectin expression in both endothelial cells and cancer cells in human prostate cancer specimens. We conclude that ESBP-CLIO(Cy5.5) is a useful probe for imaging E-selectin associated with the LLC tumor, and that E-selectin is expressed not only on endothelial cells but also on LLC cells and human prostate cancer specimens.

Animals↗

PubMed2004

Detection of invasive colon cancer using a novel, targeted, library-derived fluorescent peptide.

Sensitive methods to detect the earliest forms of colorectal cancers remain a challenge despite the development of serum and stool biomarkers. We reasoned that fluorescent affinity ligands derived from library screens can be developed to improve the detection and localization of early malignant lesions by endoscopy. We have developed an imaging agent for real-time endoscopic tumor detection in a murine model using a previously identified phage library-derived colon cancer-specific cyclic peptide and fluorescent moieties. The modified peptide had a 24 minute blood half life and tumoral accumulation was 6.9% of injected dose/g, approximately 7-fold higher than a scrambled control peptide. Orthotopic colonic tumors (HT29) were readily detectable by fluorescence endoscopy even when tumors were submucosal. These results show proof-of-principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means.

Adenoma↗

PubMed2003

Protease sensors for bioimaging.

Optical imaging of specific molecular targets and pathways in vivo has recently become possible through continued developments in imaging equipment, reconstruction algorithms, and more importantly the availability of imaging reporter molecules. These reporter molecules encompass photoproteins expressed in vivo and exogenously administered probes detectable by fluorescence and/or bioluminescence imaging. One particularly enticing aspect of optical imaging is the ability to design activatible probes with inherent amplification. This review summarizes our experience in developing novel near-infrared fluorescent (NIRF) imaging agents that report on protease activities. These agents are designed to be biocompatible, highly activatible, and able to produce bright NIRF following protease cleavage.

Animals↗

PubMed2003

Flow monitoring: performance characteristics of ultrasound dilution versus color Doppler ultrasound compared with fistulography.

BACKGROUND: Measurement of access blood flow is the preferred noninvasive screening test for hemodialysis arteriovenous (AV) fistula stenosis. However, performance characteristics of the 2 most frequently used ultrasound techniques compared with fistulography remain elusive. METHODS: We evaluated 59 hemodialysis patients with native forearm AV fistulae who underwent all 3 measurements in a prospective order: the ultrasound dilution technique (UDT), color Doppler ultrasonography (CDUS), and fistulography. Patients with angiographically diagnosed access stenosis underwent angioplasty and were followed up by means of monthly UDT measurements until restenosis occurred within the first 6 months. RESULTS: Both ultrasound techniques predicted access stenosis (P < 0.01). Performance was similar between both techniques, evaluated by receiver operating characteristic curves. Areas under the curve averaged 0.79 (95% confidence interval [CI], 0.66 to 0.91) for UDT and 0.80 (95% CI, 0.65 to 0.94) for CDUS. Correlation between measured UDT and CDUS blood flow rates was 0.37 (Spearman's rho, rho = 0.004). The calculated optimal cutoff value for the prediction of stenosis was 465 mL/min for the UDT and 390 mL/min for the CDUS technique. Access stenosis was diagnosed in 41 patients who subsequently underwent percutaneous angioplasty (PTA), which was successful in 34 patients. Restenosis occurred in 13 patients within the first 6 months after PTA. UDT access blood flow after PTA was significantly lower in these 13 patients compared with the other 21 patients. CONCLUSION: Our data suggest that blood flow monitoring of AV hemodialysis access by ultrasound provides a reasonable prediction of access stenosis and restenosis.

Adult↗

PubMed2003

Elective and emergent endovascular treatment of subclavian artery aneurysms and injuries.

PURPOSE: To demonstrate our short and long-term results after transbrachial treatment of subclavian artery aneurysms and injuries with stent-grafts in elective and emergency settings. METHODS: Ten of 12 consecutive patients (6 men; mean age 63.8 years, range 38-80) were treated electively with commercially prepared endografts delivered via a transbrachial access to repair a subclavian artery aneurysm (n=3) or an injury from a misplaced central venous catheter (n=7). Two patients required emergency treatment for a ruptured atherosclerotic aneurysm in one and an unintentional arterial puncture during placement of a central venous access in the other. Stent-graft patency during follow-up was assessed by physical examination with comparison of brachial blood pressures in all patients; computed tomography angiography (CTA) was performed in available patients. RESULTS: Successful deployment of stent-grafts with sealing of the lesion was achieved in all cases. There were 2 (17%) procedural complications. One patient developed an access-site hematoma that required surgical revision. The second patient, who had a right subclavian injury, suffered an embolic cerebral infarction. The primary stent-graft patency during follow-up (mean 11.6 months) was 100%. CTA examinations in 7 patients at a mean 18 months showed strut dislocation at the thoracic outlet without luminal narrowing in 1 patient. A 50% intraluminal narrowing due to compression between the clavicle and the first rib occurred in another patient. Six patients with a mean follow-up of 23 months (range 0.3-4.5 years) are still alive with patent stent-grafts. CONCLUSIONS: Endovascular stent-graft treatment of subclavian artery aneurysms and injuries is a less invasive alternative to surgical repair. Long-term results must still be confirmed in further studies.

Adult↗

PubMed2003

Elective endovascular stent-graft repair of atherosclerotic thoracic aortic aneurysms: clinical results and midterm follow-up.

OBJECTIVE: The purpose of this study was to evaluate the clinical and midterm results after endovascular treatment of atherosclerotic thoracic aortic aneurysms. MATERIALS AND METHODS: Twenty-eight consecutive patients who were 53-82 years old (mean age, 71.6 years) were treated with a commercially available endoprosthesis. Subclavian transposition or bypass surgery was performed before the procedure in eight patients. Size dynamics of the aneurysms were analyzed on the basis of diameter and thrombus volume measurements obtained on three-dimensional CT reconstructions before hospital discharge (n = 22) and at the 1-year (n = 22), 2-year (n = 12), and 3-year (n = 5) follow-ups. RESULTS: The technical success rate was 100%. There was no 30-day mortality. None of the patients had symptoms due to spinal cord ischemia. The survival rate at 1, 2, and 3 years was 96.1%, 90.9%, and 80.2%, respectively. During the perioperative period, patients presented with leukocytosis (37%), fever (36%), elevated C-reactive protein value (92%), pleural effusion (50%), and periaortic atelectasis (41%). Three early type I endoleaks sealed spontaneously. Three early type II endoleaks persisted over time, and one late type II endoleak was detected. In patients with type II endoleaks, thrombus volume of the aneurysms was constant (n = 2) or increased (n = 2). In patients without endoleaks, mean thrombus volume decreased (-53.2 +/- 56.8 mL, -40%) significantly (p = 0.001) during the first year. There was no significant interval decrease between the 1- and 2-year follow-ups (mean, -2.4 mL, p = 0.92) and between the 2- and 3-year follow-ups (mean, -0.4 mL, p = 0.68). CONCLUSION: Endovascular treatment of atherosclerotic thoracic aortic aneurysms may result in a substantial reduction of the aneurysm sac in patients without endoleaks.

Aged↗

PubMed2002

Vertebral metastases: assessment with apparent diffusion coefficient.

The authors evaluated the apparent diffusion coefficient (ADC) in the assessment of vertebral metastases and acute vertebral compression fractures in 22 patients with known or suspected vertebral metastases. On the basis of significantly (P <.03) different ADCs, vertebral metastases (0.69 x 10(-3) mm2/sec) and pathologic compression fractures (0.65 x 10(-3) mm2/sec) can be safely distinguished from vertebral bodies (1.66 x 10(-3) mm2/sec) and benign compression fractures (1.62 x 10(-3) mm2/sec). Thus, the use of ADCs may increase the specificity of magnetic resonance imaging in these patients.

Echo-Planar Imaging↗