CAR T-cells targeting FGFR4 and CD276 simultaneously show potent antitumor effect against childhood rhabdomyosarcoma.

Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here we report an optimization strategy of the co-stimulatory and targeting properties of a FGFR4 CAR. We replace the CD8 hinge and transmembrane domain and the 4-1BB co-stimulatory domain with those of CD28.

Preclinical development of a chimeric antigen receptor T cell therapy targeting FGFR4 in rhabdomyosarcoma.

Pediatric patients with relapsed or refractory rhabdomyosarcoma (RMS) have dismal cure rates, and effective therapy is urgently needed. The oncogenic receptor tyrosine kinase fibroblast growth factor receptor 4 (FGFR4) is highly expressed in RMS and lowly expressed in healthy tissues. Here, we describe a second-generation FGFR4-targeting chimeric antigen receptor (CAR), based on an anti-human FGFR4-specific murine monoclonal antibody 3A11, as an adoptive T cell treatment for RMS.

Optimizing evaluation in pediatric and young adult patients with Marfan syndrome: Novel longitudinal metrics to track growth of aortic structures.

Objective: Surveillance metrics in pediatric and young adult Marfan syndrome (pMFS) are challenging. We evaluated the utility of aortic root cross-sectional area/height index (CSA/Ht) on echocardiogram among pMFS patients as a risk stratification and surgical triage metric.

Methods: Genotype or phenotype positive pMFS patients aged 25 years or younger seen at our center from 2001 to 2020 were identified.

Hyperthermia-mediated changes in the tumor immune microenvironment using iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have often been investigated for tumor hyperthermia. IONPs act as heating foci in the presence of an alternating magnetic field (AMF). It has been shown that hyperthermia can significantly alter the tumor immune microenvironment.

Ability of the surgical Apgar score to predict acute kidney injury following radical cystectomy.

Purpose: Acute kidney injury (AKI) is a common complication after radical cystectomy (RC). Previous literature has shown that intraoperative hemodynamic instability measured via the surgical Apgar score is an independent predictor of major complications following RC. We sought to determine whether the surgical Apgar score is predictive of postoperative AKI.

PTPmu-targeted nanoparticles label invasive pediatric and adult glioblastoma.

Poor prognosis for glioblastoma (GBM) is a consequence of the aggressive and infiltrative nature of gliomas where individual cells migrate away from the main tumor to distant sites, making complete surgical resection and treatment difficult. In this manuscript, we characterize an invasive pediatric glioma model and determine if nanoparticles linked to a peptide recognizing the GBM tumor biomarker PTPmu can specifically target both the main tumor and invasive cancer cells in adult and pediatric glioma models. Using both iron and lipid-based nanoparticles, we demonstrate by magnetic resonance imaging, optical imaging, histology, and iron quantification that PTPmu-targeted nanoparticles effectively label adult gliomas.

Electroacupuncture Versus Aerobic Interval Training on Liver Functions in Patients with Nonalcoholic Fatty Liver.

Nonalcoholic fatty liver disease (NAFLD) is considered one of the most common and most important conditions affecting the liver, because of its increasing prevalence all over the world. It is usually associated with elevated liver enzymes and ranges from simple steatosis to liver cirrhosis. This study was conducted to compare the effects of electroacupuncture (EA) versus aerobic interval training (AIT) exercise and how they affect liver functions in people suffering from nonalcoholic fatty liver.

Effect of Dose and Selection of Two Different Ligands on the Deposition and Antitumor Efficacy of Targeted Nanoparticles in Brain Tumors.

Deposition of nanoparticles to tumors often can be enhanced by targeting receptors overexpressed in a tumor. However, a tumor may exhibit a finite number of a biomarker that is accessible and targetable by nanoparticles, limiting the available landing spots. To explore this, we selected two different biomarkers that effectively home nanoparticles in brain tumors.

Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells.

Imaging breast cancer using a dual-ligand nanochain particle.

Nanoparticles often only exploit the upregulation of a receptor on cancer cells to enhance intratumoral deposition of therapeutic and imaging agents. However, a single targeting moiety assumes that a tumor is homogenous and static. Tumoral microenvironments are both heterogenous and dynamic, often displaying variable spatial and temporal expression of targetable receptors throughout disease progression.

Early CT and FDG-metabolic tumour volume changes show a significant correlation with survival in stage I-III small cell lung cancer: a hypothesis generating study.

Background: Many patients with stage I-III small cell lung cancer (SCLC) experience disease progression short after the completion of concurrent chemoradiotherapy (CRT). The purpose of the current study was to evaluate whether CT or FDG metabolic response early after the start of chemotherapy, but before the beginning of chest RT, is predictive for survival in SCLC.

Methods: Fifteen stage I-III SCLC patients treated with concurrent CRT with an FDG-PET and CT scan available before the start of chemotherapy and after or during the first cycle of chemotherapy, but before the start of radiotherapy, were selected.

Correlation of Technetium-99m scintigraphy, progressive acetabular osteolysis and acetabular component loosening in total hip arthroplasty.

In total hip arthroplasty (THA) Technetium scintigraphy can help to diagnose a loose implant by detecting elevated osteoblastic activity. It has been used for timing the revision of cemented implants. In uncemented cups progressive radiological acetabular osteolysis can be present before loosening accurs, but it is probably unwise to await cup loosening before embarking on revision.

Tumor volume combined with number of positive lymph node stations is a more important prognostic factor than TNM stage for survival of non-small-cell lung cancer patients treated with (chemo)radiotherapy.

Purpose: The current tumor, node, metastasis system needs refinement to improve its ability to predict survival of patients with non-small-cell lung cancer (NSCLC) treated with (chemo)radiation. In this study, we investigated the prognostic value of tumor volume and N status, assessed by using fluorodeoxyglucose-positron emission tomography (PET).

Patients And Methods: Clinical data from 270 consecutive patients with inoperable NSCLC Stages I-IIIB treated radically with (chemo)radiation were collected retrospectively.

Preoperative bone quality as a factor in dual-energy X-ray absorptiometry analysis comparing bone remodelling between two implant types.

Recently it was shown that the design changes from the ABG-I to ABG-II hip stem resulted in a better, although not significant, proximal bone preservation. Our hypothesis was that by matching patients for preoperative bone quality, statistical power would increase and that the trend of better proximal bone preservation in ABG-II might become significant. Twenty-four ABG-II patients were compared to two different ABG-I groups: (1) 25 patients from our earlier prospective study and (2) a group of 24 patients selected to perfectly match the ABG-II group regarding gender, age and preoperative bone quality.

The influence of implant design on periprosthetic bone remodelling of two types of uncemented HA-coated hip stems. A two-year follow-up study using DEXA.

Unlabelled: Proximal bone resorption and an increased fracture rate in the ABG-I stem has been shown. For these reasons the ABG-I stem design was changed to the ABG-II. In this study periprosthetic bone loss around the ABG-I vs ABG-II is compared to verify if the design changes resulted in improved proximal bone preservation.

High survival rate of hydroxyapatite-coated hip prostheses: 100 consecutive hips followed for 10 years.

We followed 100 consecutive primary total hip replacements with a proximal hydroxyapatite coating for 10 years. No patient was lost to follow-up. 29 patients (32 hips) died before the 10-year follow-up was done; none of their hips had been revised.

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm.

Multiparameter flow cytometry as a tool for the detection of micrometastatic tumour cells in the sentinel lymph node procedure of patients with breast cancer.

Aim: To investigate whether multiparameter flow cytometry (MP-FCM) can be used for the detection of micrometastasis in sentinel lymph nodes (SLNs) in breast cancer.

Methods: Formalin fixed, paraffin wax embedded sentinel lymph nodes (n = 238) from 98 patients were analysed. For each lymph node, sections for haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) for cytokeratin (MNF116) were cut at three levels with a distance of 500 microm.

Hydroxyapatite-coated acetabular components. Histological and histomorphometric analysis of six cups retrieved at autopsy between three and seven years after successful implantation.

Background: Important questions remain regarding the use of hydroxyapatite-coated acetabular components in total hip arthroplasty. What is the relation of resorption of the hydroxyapatite coating to enduring fixation? Will unresorbed or dislodged hydroxyapatite particles cause adverse tissue reactions? Retrieval studies of clinically well-functioning acetabular components should help to answer these questions.

Methods: We examined six clinically successful hydroxyapatite-coated cementless acetabular components that were retrieved at autopsy between 3.

Hydroxyapatite coated hip prosthesis followed up for 5 years.

We prospectively studied 250 patients with a proximal hydroxyapatite coated hip prosthesis. The follow-up period was 5 years. All components showed osseointegration except for one deep infection.

The hydroxyapatite-ABG hip system: 5- to 7-year results from an international multicentre study. The International ABG Study Group.

A proximally hydroxyapatite (HA)-coated hip prosthesis designed for proximal stem bonding and stress transfer was studied in a consecutive series of 398 patients in an ongoing, prospective multicenter study. Follow-up was 5 to 7 years. The clinical results were excellent with a mean preoperative Merle d'Aubigné score of 8.

Quantitative analysis of technetium-99m-methylene diphosphonate uptake in unilateral hydroxyapatite-coated total hip prostheses: first year of follow-up.

Unlabelled: A prospective study was performed on 80 patients who had undergone a unilateral hydroxyapatite (HA)-coated total hip arthroplasty to establish the normal periprosthetic uptake of methylenediphosphonate (MDP) as a function of implant age.

Methods: Patients were imaged periodically while they were asymptomatic at 1, 3, 6 and 12 mo postoperatively. Quantitative measurements were performed with a region of interest (ROI) technique.

Pneumocystis carinii: recognition of the infection in albino rats using different stains.

Pneumocystis carinii is a commensal protozoan which may cause pneumonia in hosts with compromised immune status and may end fatally. Since effective management of pneumocystic pneumonia depends on rapid and accurate recognition of the disease, so, the present study aims to throw lights on the best staining method for cytodiagnosis of this organism with the sequential pathological changes in the infected lungs. An immunosuppression state was induced in albino rats for 6-8 weeks then rats were sacrificed weekly & lungs were examined for infection using different stains.