Targeted intracellular delivery of dimeric STINGa by two pHLIP peptides for treatment of solid tumors.

We have developed a delivery approach that uses two pHLIP peptides that collaborate in the targeted intracellular delivery of a single payload, dimeric STINGa (dMSA). dMSA was conjugated with two pHLIP peptides via S-S cleavable self-immolating linkers to form 2pHLIP-dMSA. Biophysical studies were carried out to confirm pH-triggered interactions of the 2pHLIP-dMSA with membrane lipid bilayers.

pHLIP targeted intracellular delivery of calicheamicin.

Calicheamicin is a potent, cell-cycle independent enediyne antibiotic that binds and cleaves DNA. Toxicity has led to its use in a targeted form, as an antibody-drug conjugate approved for the treatment of liquid tumors. We used a reduced calicheamicin to conjugate it to a single cysteine residue at the membrane-inserting end of a pH Low Insertion Peptide (pHLIP) that targets imaging and therapeutic agents to tumors.

Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors.

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al.

Tumor treatment by pHLIP-targeted antigen delivery.

Targeted antigen delivery allows activation of the immune system to kill cancer cells. Here we report the targeted delivery of various epitopes, including a peptide, a small molecule, and a sugar, to tumors by pH Low Insertion Peptides (pHLIPs), which respond to surface acidity and insert to span the membranes of metabolically activated cancer and immune cells within tumors. Epitopes linked to the extracellular ends of pH Low Insertion Peptide peptides were positioned at the surfaces of tumor cells and were recognized by corresponding anti-epitope antibodies.

Comparison of Retinal Imaging Techniques in Individuals with Pulmonary Artery Hypertension Using Vessel Generation Analysis.

(1) Background: Retinal vascular imaging plays an essential role in diagnosing and managing chronic diseases such as diabetic retinopathy, sickle cell retinopathy, and systemic hypertension. Previously, we have shown that individuals with pulmonary arterial hypertension (PAH), a rare disorder, exhibit unique retinal vascular changes as seen using fluorescein angiography (FA) and that these changes correlate with PAH severity. This study aimed to determine if color fundus (CF) imaging could garner identical retinal information as previously seen using FA images in individuals with PAH.

Targeting Bladder Urothelial Carcinoma with pHLIP-ICG and Inhibition of Urothelial Cancer Cell Proliferation by pHLIP-amanitin.

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers.

D-dimer Testing in Pulmonary Embolism with a Focus on Potential Pitfalls: A Narrative Review.

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process.

Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA -rearranged lung adenocarcinoma who developed a A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity.

Eradication of tumors and development of anti-cancer immunity using STINGa targeted by pHLIP.

Despite significant progress in the development of novel STING agonists (STINGa), applications appear to be challenged by the low efficiency and poor selectivity of these agents. A pH Low Insertion Peptide (pHLIP) extends the lifetime of a STINGa in the blood and targets it to acidic cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid derived suppressor cells (mMDSCs) and dendritic cells (DCs). CAFs constitute 25% of all live cells within CT26 tumors, and M2-type TAMs and mMDSCs are the most abundant among the immune cells.

pHLIP Peptides Target Acidity in Activated Macrophages.

Purpose: Acidity can be a useful alternative biomarker for the targeting of metabolically active cells in certain diseased tissues, as in acute inflammation or aggressive tumors. We investigated the targeting of activated macrophages by pH low insertion peptides (pHLIPs), an established technology for targeting cell-surface acidity.

Procedures: The uptake of fluorescent pHLIPs by activated macrophages was studied in cell cultures, in a mouse model of lung inflammation, and in a mouse tumor model.

Abdominal CT findings in Puumala hantavirus-infected patients.

Background: Previous clinical studies have reported abdominal findings on ultrasonography or MRI in Puumala hantavirus-infected patients.

Purpose: To determine if abdominal computed tomography (CT) can lead to a diagnosis of Puumala virus infection in the presence of a suggestive clinical picture.

Material And Methods: CT findings were studied retrospectively in 30 patients who presented to the emergency department of two (Belgian) hospitals with serologically confirmed Puumala hantavirus infection.

Cardiac CT findings in patients with family history of premature CAD: an observational study.

Introduction: A family history of premature CAD may promote enhanced development of coronary atherosclerosis in a sibling population. Baseline CV algorithms may underestimate the risk of coronary incidents in individuals at familial risk. Cardiac CT provides high diagnostic performance for the detection of coronary plaques.

Subgaleal Lipoma: Imaging Findings.

Unlabelled: Subgaleal lipoma is a benign tumor of adipose tissue. It should be suspected when a semi-spherical avascular mass with well-defined margins, iso- or hyperechoic in most cases, with thin internal echogenic lines parallel to the long axis of the tumor, is observed between the galea aponeurosis and periosteum of the cranial bone. We report a series of cases of three patients who underwent surgical lesion excision and whose histopathological examination findings confirmed the diagnosis of lipoma.

Presacral Myelolipoma: The Usefulness of a 99mTc-Albumin Nanocolloid Scintigraphy.

Myelolipoma is a rare mesenchymal tumor consisting of adipose tissue and hematopoietic cells. Found usually in the adrenal region, however, few cases have been reported in extra-adrenal regions, most frequently in the presacral region. It is important to recognize such tumor, as it can attain massive size and causes pressure symptoms, and needs to be differentiated from malignant tumors, including liposarcomas.

Anatomy and external landmarks of the superficial temporal artery using 3-dimensional computed tomography.

Purpose: The purpose of this study was to analyze the anatomical variability of the superficial temporal artery (STA) and to provide an easy visual landmark to find the STA and its branches to facilitate its surgical access.

Methods: A retrospective study was conducted on 57 patients who underwent a head and neck computed tomography with contrast injection. A visual landmark running from the tragus to the corner of the eye was used: the "eye-tragus-line" (ETL).

pHLIP ICG for delineation of tumors and blood flow during fluorescence-guided surgery.

Fluorescence imaging has seen enduring use in blood flow visualization and is now finding a new range of applications in image-guided surgery. In this paper, we report a translational study of a new fluorescent agent for use in surgery, pHLIP ICG, where ICG (indocyanine green) is a surgical fluorescent dye used widely for imaging blood flow. We studied pHLIP ICG interaction with the cell membrane lipid bilayer, the pharmacology and toxicology in vitro and in vivo (mice and dogs), and the biodistribution and clearance of pHLIP ICG in mice.

Early Chest Imaging in Patients with Puumala Hantavirus Infection.

Purpose: To describe early chest imaging abnormalities in patients with acute Puumala virus infection.

Materials And Methods: This retrospective study (2005-2017) comprised 64 patients who were admitted to the emergency department of a Belgian hospital. These patients were diagnosed with serologically confirmed acute Puumala virus infection and had at least one chest X-ray (CRX).

Systematic scrotum ultrasound in male infertility: what to look for.

Ultrasound is a useful, cost-effective and minimally invasive tool that can be used in the workup of male infertility. Patient history, semen analysis and hormonal results often precede ultrasound examination as a part of the workup of male factor infertility.In our article, we advocate the added value of a systematic approach of the scrotal ultrasound.

Puumala hantavirus: an imaging review.

Puumala virus (PUUV) is the most common hantavirus in Europe. It is known to cause nephropathia epidemica, which is considered a mild type of hemorrhagic fever with renal syndrome. However, it does not only involve the kidneys and is rarely accompanied by symptomatic hemorrhage.

A Patient with GOLD Stage 3 COPD « cured » by One-Way Endobronchial Valves.

Lung hyperinflation is a main determinant of dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Surgical or bronchoscopic lung volume reduction are the most efficient therapeutic approaches for reducing hyperinflation in selected patients with emphysema. We here report the case of a 69-year old woman with COPD (GOLD stage 3-D) referred for lung volume reduction.

Cardiac computed tomography in asymptomatic siblings of patients with premature coronary disease: illustrations and current knowledge.

A strong family history of early-onset coronary artery disease (CAD) may represent a substantial predictor of enhanced development of subclinical atherosclerosis in a sibling population. In this population, standard cardiovascular (CV) risk assessment could be underrated with the predictive capacity of the Framingham Risk Score. At present, cardiac computed tomography (CT) provides a high diagnostic performance for the detection of coronary atherosclerosis.

Cytotoxic Lesion of the Corpus Callosum Caused by Puumala Hantavirus Infection.

We report the case of a 45-year-old male referred to our hospital with fever, asthenia, visual disturbances and increasing headaches. Diffusion-weighted imaging of the brain showed high signal intensity in the splenium of corpus callosum with low apparent diffusion coefficient values. Diagnosis of cytotoxic lesion of corpus callosum was made with Puumala Hantavirus infection serologically confirmed and should not be mistaken for ischemia.