Search

Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post-transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles (PVP-SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP-SPIO-labeled NPI in an agarose gel was visualized clearly by MRI. PVP-SPIO-labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP-SPIO-labeled islets reached normoglycemia. Grafts appeared as hypo-intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP-SPIO did not affect the function of NPI that PVP-SPIO-labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP-SPIO-labeled islets to monitor graft viability.

To discriminate pathological from physiological hydronephrosis (99m)Tc-mercaptoacetyltriglycine (MAG3) diuretic renography is a fundamental imaging modality. Initial asymmetrical differential function or decreasing function on serial MAG3 scans is a classic surgical indication. However, prognostic evidence supporting this is limited. Therefore, we examined the association between initial function and outcomes. We hypothesized that patients with initially asymmetrical function would have higher odds of functional decline, and experience symptoms and surgical intervention compared to patients with initially symmetrical scans.We retrospectively reviewed the charts of 1,124 pediatric patients with hydronephrosis seen at Stollery Children's Hospital from 2000 to 2014. A total of 387 cases of unilateral ureteropelvic junction obstruction were grouped by initial postnatal differential function with asymmetrical defined as a greater than 10% difference in relative function. Postnatal surveillance, followup MAG3 results, pyeloplasty rates and post-pyeloplasty outcomes were compared.Of 387 patients 143 (37%) had initially asymmetrical function. Of those undergoing MAG3 scan surveillance 17% experienced a 10% or greater decline in ipsilateral differential function vs a 6% rate of function loss in the initially symmetrical group (OR 3.2, 95% CI 1.6-6.4, p = 0.0008). The overall pyeloplasty rate in patients with asymmetrical and symmetrical function was 27% and 16%, respectively (OR 1.9, 95% CI 1.1-3.2, p = 0.013). Patients with initially asymmetrical function had an increased rate of pyeloplasty secondary to symptoms compared to those with initially symmetrical function (16% vs 8%, OR 2.1, 95% CI 1.1-4.0, p = 0.019). Mean time to functional decline and pyeloplasty was 19 and 17 months, respectively.Patients with initially asymmetrical differential function had increased ORs for subsequent renal decline, symptom onset and pyeloplasty.

Current protocols to determine optimal nulling time in late enhancement imaging using adult techniques may not apply to children. To determine the optimal nulling time in anesthetised children, with the hypothesis that this occurs earlier than in adults. Sedated cardiac MRI was performed in 12 children (median age: 12 months, range: 1–60 months). After gadolinium administration, scout images at 2, 3, 4 and 10 min and phase sensitive inversion recovery (PSIR) images from 5 to 10 min were obtained. Signal-to-noise ratio (SNR) and inversion time (TI) were determined. Quality of nulling was assessed according to a grading score by three observers. Data was analysed using linear regression, Kruskal-Wallis and quadratic-weighted kappa statistics. One child with a cardiomyopathy had late enhancement. Good agreement in nulling occurred for scout images at 2 (κ = 0.69) and 3 (κ = 0.66) min and moderate agreement at 4 min (κ = 0.57). Agreement of PSIR images was moderate at 7 min (κ = 0.44) and poor-fair at other times. There were significant correlations between TI and scout time (r = 0.61, P

The interaction of dendritic cells (DCs) and T cells has been the cornerstone of approaches to cancer immunotherapy. Antitumoral immune responses can be elicited by delivering cancer antigens to DCs. As antigen presenting cells, these DCs activate cancer antigen specific T cells. Whereas the first part of the review discusses methods for delivery of cancer vaccines to DCs, in this part the focus is on the potential role of nanoscopic devices for molecular imaging of these immune responses. Nanoscopic devices could potentially deliver tracking molecules to DCs, enabling monitoring of DCs and/or T cell activation and tumoricidal activity during immunotherapy, using non-invasive imaging modalities such as nuclear imaging (single photon emission computed tomography (SPECT), positron emission tomography (PET)), magnetic resonance imaging (MRI) and optical imaging.

Dendritic cells (DCs) are the key antigen presenting cells that link innate and adaptive immunity. In the periphery, DCs capture antigens, process them and migrate into the regional lymph nodes where they could initiate antigen specific T cell immune responses. Immunotherapeutic strategies that aim to deliver tumor antigens specifically to DCs could not only boost anti-tumor immune responses but also could alleviate non-specific immune activation and/or unwanted side effects. Nano-sized particulate delivery systems are efficient modalities that can deliver tumor antigens to DCs in a targeted and specific manner. This review will provide general information on the rationale behind targeting antigens to DCs and the crucial role of DCs in initiating antigen specific T cell responses. Different strategies that have been employed in delivering antigens to DCs will be also discussed. A special emphasis will be put on specific targeting of cancer vaccine formulations to DC-specific receptors (e.g. CD11c, CD40, Fcγ, CCR6, pathogenic recognition receptors such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs)).

The purpose of this study was to identify an optimum targeted particulate formulation based on mannan (MN)-decorated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), for efficient delivery of incorporated cargo to dendritic cells (DCs). In brief, NPs were formulated from two different types of PLGA; ester-terminated (capped) or COOH-terminated (uncapped) polymer. Incorporation of MN in NPs was achieved either through addition of MN during the process of NP formation or by attachment of MN onto the surface of the freeze dried NPs by physical adsorption or chemical conjugation (to COOH terminated polymer). The formulated NPs were characterized in terms of particle size, Zeta potential and level of MN incorporation. The effect of polymer type and the incorporation method on the extent of fluorescently labelled NP uptake by murine bone marrow-derived DCs have been investigated using flowcytometry. The results of this study showed MN incorporation to enhance the uptake of PLGA NPs by DCs. Among different MN incorporation strategies, covalent attachment of MN to COOH-terminated PLGA-NPs provided the highest level of MN surface decoration on NPs. Maximum NP uptake by DCs was achieved by COOH terminated PLGA NPs containing covalent or adsorbed MN. Therefore, a better chance of success for these formulations for active targeted drug and/or vaccine delivery to DCs is anticipated.

A 63-year-old male was found to have a 7.5-cm splenic mass that had imaging appearances of an atypical haemangioma on CT, ultrasound and a 99mTc-RBC scan, and he was followed conservatively with serial ultrasounds. Sixteen months later, however, the splenic lesion grew and he developed numerous new liver masses which were biopsy confirmed to be a pleomorphic spindle cell sarcoma (PSCS), formerly known as malignant fibrous histiocytoma (MFH). A staging 18F-FDG PET/CT was performed and showed innumerable, mostly necrotic hepatic and splenic masses. The patient passed away a few days after the PET/CT, before a treatment program could be implemented. The use of 18F-FDG PET/CT in the staging of splenic PSCS has not been previously described. We present the 99mTc-RBC and 18F-FDG PET/CT image characteristics of a patient with splenic PSCS.

sporadic head and neck paragangliomas often represent familial paraganglioma syndrome (FPS). FPS patients require close follow-up, and family members will benefit from screening. No clear guideline for following these patients exists in the otolaryngology literature.to present a series of FPS patients, illustrating the importance of a cost-effective FPS genetic screening algorithm applicable in otolaryngology.case series, literature review, clinical guidelines.tertiary care hospital.adult patients with SDHx mutations were identified in the University of Alberta's head and neck mass database. Medical records were reviewed for presentation, diagnosis, findings, treatment, follow-up, and genetic testing. A literature review of FPS clinical features, treatment, and genetic screening methods was performed.genetic screening.cost-effectiveness of genetic testing for FPS screening.two patients with FPS were surgically treated by otolaryngologists. All patients presented with multifocal disease and carried SDHB or SDHD mutations. A screening and genetic testing protocol was implemented leading to early detection in a third patient, thus reducing morbidity. The literature review supports the contention that all patients with head and neck paragangliomas should undergo genetic testing. An algorithm to screen such patients is proposed. Cost analysis showed savings of over $2400 ($US 2200) every 6 years with this approach.owing to the potential morbidity associated with head and neck paragangliomas, it is prudent that FPS be ruled out. Those found to have SDHx mutations, and first-degree relatives, should be offered genetic testing with enrolment in a screening protocol. This provides a cost-effective, early detection approach to FPS.

Methods Sedated cardiac MRI was performed on a 1.5 T Siemens Sonata. After IV injection of 0.2 mmol/kg of gadolinium (Magnovist), scout images were obtained at 2, 3, 4 and 10 minutes, and turboFLASH PSIR were obtained using standard views at 5-9 minutes. All images were assessed according to a grading score: 0 = none; 1 = reverse; 2 = poor; 3 = partial; and 4 = good nulling. The inversion time (TI) was determined from the best nulled scout image. Images were analysed by 3 independent observers blinded to the clinical information. The mean and standard deviation of the grading score was analysed using the KruskalWallis analysis and interobserver variability was determined by quadratic weighted kappa statistics.

Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for the delivery of JSI-124 (a small molecule inhibitor of STAT3) to tumor and immunosuppressed DCs using poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs). For this purpose, JSI-124 was chemically conjugated to PLGA and the PLGA-JSI-124 conjugate was formulated into nanoparticles using the emulsification solvent evaporation method. The attachment of JSI-124 to PLGA was confirmed by a combination of thin layer chromatography and (1)H NMR. The level of JSI-124 in NPs, determined by liquid chromatography-mass spectrometry, was found to be 1.7 +/- 0.3 microg per mg of PLGA. The PLGA-JSI-124 NPs demonstrated a controlled drug release profile over a 1-month period and exhibited potent anticancer and STAT3 inhibitory activity comparable to the soluble JSI-124 after 24 h incubation with B16 melanoma cells, in vitro. Moreover, PLGA-JSI-124 NPs efficiently suppressed the level of p-STAT3 in p-STAT3(high) DCs, generated from mouse bone marrow cells in the presence of conditioned media of B16 cells (B16CM-DCs), and improved their function as assessed by mixed lymphocyte reaction (MLR). Specifically cotreatment of B16CM-DCs with PLGA-JSI-124 NPs and PLGA NPs containing the DC adjuvant CpG resulted in higher levels of T cell proliferation in the MLR assay compared with B16CM-DCs untreated or treated with either CpG NPs or JSI-124 NPs alone. Our results indicate that PLGA NPs containing conjugated JSI-124 can potentially provide a useful platform for sustained JSI-124 release in tumor and its targeted delivery to DCs leading to the modulation of anticancer response by JSI-124 in tumor cells and immunosuppressed DCs, in vitro.

Development of safe and effective cancer vaccine formulation is a primary focus in the field of cancer immunotherapy. The recognition of the crucial role of dendritic cells (DCs) in initiating anti-tumor immunity has led to the development of several strategies that target vaccine antigens to DCs as an attempt for developing potent, specific and lasting anti-tumor T cell responses. The main objective of this review is to provide an overview on the application of poly (d,l-lactic-co-glycolic acid) nanoparticles (PLGA-NPs) as cancer vaccine delivery system and highlight their potential in the development of future therapeutic cancer vaccines. PLGA-NPs containing antigens along with immunostimulatory molecules (adjuvants) can not only target antigen actively to DCs, but also provide immune activation and rescue impaired DCs from tumor-induced immuosupression.