Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.     

Oral and maxillofacial manifestations of Gardner's syndrome associated with growth hormone deficiency: case report and literature review

Gardner's syndrome (GS) is a hereditary disorder inherited as autosomal dominant with complete penetrance and variable expression. GS is a variant of familial adenomatous polyposis characterized by extracolonic manifestations including osteomas, dental anomalies, and epidermoid cysts. The association between GS and endocrine abnormalities has been well documented but a direct pituitary involvement has never been reported. We present a case of oral and maxillofacial manifestations in an adult patient affected by GS associated with growth hormone deficiency, a hitherto unreported association. The possible pathogenic mechanisms are discussed.     

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic,multicenter cross-sectional cohort study

Background

The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities.

Methods

Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry.

Findings

A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007).

Interpretation

When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options.     

Evaluation of the Cyclic Fatigue of Two Single Files at Body and Room Temperature with Different Radii of Curvature

Background: To compare the influence of different temperatures and curvature radii on the cyclic fatigue resistance of F6 SkyTaper (F6ST) and One Curve (OC) single file nickel-titanium rotary instruments. Methods: A total of 120 instruments of F6ST and OC #25.06 were evaluated in 5 mm and 3 mm curvature radii at two temperatures (20 °C ± 1 °C and 37 °C ± 1 °C) in 16 mm stainless steel artificial canals associated with a curvature of 60°. The cyclic fatigue of tested files was assessed by employing a customized testing apparatus and expressed as times to fracture (TtF). A statistical analysis was performed with the significance level set at 95%. Results: All instruments decreased their TtF at 37 °C except for OC in the 3 mm radius, in which no significant difference was detected between 20 °C and 37 °C. A 3 mm curvature radius negatively affected TtF of all tested instruments, except for F6ST at 20 °C. F6ST had higher TtF than OC in the 3 mm radius at 20 °C, with no significant difference between them in the other tested conditions. Conclusions: Under the limits of the present in vitro study, body temperature impaired cyclic fatigue resistance of all files, except for OC in the 3 mm curvature radius. All instruments exhibited lower times to fracture in the 3 mm radius, excluding F6ST at 20 °C.     

Phage-Displayed Peptides for Targeting Tyrosine Kinase Membrane Receptors in Cancer Therapy

Receptor tyrosine kinases (RTKs) regulate critical physiological processes, such as cell growth, survival, motility, and metabolism. Abnormal activation of RTKs and relative downstream signaling is implicated in cancer pathogenesis. Phage display allows the rapid selection of peptide ligands of membrane receptors. These peptides can target in vitro and in vivo tumor cells and represent a novel therapeutic approach for cancer therapy. Further, they are more convenient compared to antibodies, being less expensive and non-immunogenic. In this review, we describe the state-of-the-art of phage display for development of peptide ligands of tyrosine kinase membrane receptors and discuss their potential applications for tumor-targeted therapy.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Snuffbox approach for balloon aortic valvuloplasty: A case series

In the era of transcatheter aortic valve replacement (TAVR), the spectrum of indications for balloon aortic valvuloplasty is growing, especially in old and frail patients. Mini-invasive approaches via radial access reduce vascular complications and length of hospital stay. The snuffbox approach has never been described for Balloon aortic valvuloplasty (BAV). We performed a review of patients who underwent BAV using distal radial access between January 2019 and December 2019 in a single Italian Centre. All patients received a 30-day follow-up. The procedure was successfully conducted by anatomical snuffbox in all reported cases. All patients were mobilized within 10 h from the procedure without vascular access-related complications. Thirty-day color Doppler ultrasound showed distal radial artery patency in 89% of cases. In our case series, the snuffbox approach for balloon aortic valvuloplasty appeared to be safe and feasible. This approach could be a valid alternative especially in old and frail adults waiting for TAVR.