Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip.

There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms.

Detection of Nine Oncogenes Amplification in Lung and Colorectal Cancer Formalin-Fixed Paraffin-Embedded Tissue Samples using Combined Next-Generation Sequencing-Based Script and Digital Droplet Polymerase Chain Reaction.

Introduction: Gene copy number variations have theranostic impact and require reliable methods for their identification. We aimed to evaluate the reliability of combined next-generation sequencing (NGS) and digital droplet PCR (ddPCR) method for gene amplification evaluation.

Methods: We conducted a retrospective multicentric observational study.

Autoantibodies are associated with disease progression in idiopathic pulmonary fibrosis.

Several reports have highlighted a potential role of autoreactive B-cells and autoantibodies that correlates with increased disease severity in patients with idiopathic pulmonary fibrosis (IPF). Here we show that patients with IPF have an altered B-cell phenotype and that those subjects who have autoantibodies against the intermediate filament protein periplakin (PPL) have a significantly worse outcome in terms of progression-free survival. Using a mouse model of lung fibrosis, we demonstrate that introducing antibodies targeting the endogenous protein PPL (mimicking naturally occurring autoantibodies seen in patients) directly in the lung increases lung injury, inflammation, collagen and fibronectin expression through direct activation of follicular dendritic cells, which in turn activates and drives proliferation of fibroblasts.

[Digestive infectious pathology: Diagnoses not to be missed].

The recent context of COVID-19 has renewed the interest of pathologists in diseases of infectious origin. This interest is even stronger in the gastrointestinal tract where symptoms are aspecific, often frustrating with a normal endoscopic appearance sometimes leading to diagnostic erraticity. In this context, systematic biopsies performed by the clinician are sometimes the only way to reach a diagnosis.

[Lymphocytic "…itis", from esophagus to large bowel].

Intra-epithelial lymphocytosis is an elementary lesion frequently observed in the gastrointestinal tract, which can be found from the esophagus to the colon. Many conditions of a varied nature (dysimmunitary diseases, drugs, infections…) are associated with intra-epithelial lymphocytosis, and the etiological diagnosis most often requires an anatomo-clinical correlation. The pathologist will have to identify histological lesions associated with intra-epithelial lymphocytosis allowing the diagnosis to be oriented in order to propose appropriate treatment.

Joint analysis of PK and immunogenicity outcomes using factorization model - a powerful approach for PK similarity study.

Biological products, whether they are innovator products or biosimilars, can incite an immunogenic response ensuing in the development of anti-drug antibodies (ADA). The presence of ADA's often affects the drug clearance, resulting in an increase in the variability of pharmacokinetic (PK) analysis and challenges in the design and analysis of PK similarity studies. Immunogenic response is a complex process which may be manifested by product and non-product-related factors.

A new - gene fusion in a lung adenocarcinoma patient.

https://bit.ly/3nYmGQ9.

Can neuroimaging differentiate PFO and AF-related cardioembolic stroke from the other embolic sources? Clinical-radiological correlation on a retrospective study.

Purpose: The aim of this retrospective study was to map the specific ischemic lesion patterns of distribution in patent foramen ovale-related stroke (PFO-stroke) and atrial fibrillation-related stroke (AF-stroke) in patients with idiopatic ischemic stroke.

Materials And Methods: 750 ischaemic strokes were screened on basis of diagnostic imaging and tests: patients with known causes were excluded. 171 patients with unknown cause were selected and divided in two groups: AF-stroke (43 patients) and PFO-stroke (128 patients).

Predictive value of pre-treatment apparent diffusion coefficient (ADC) in radio-chemiotherapy treated head and neck squamous cell carcinoma.

Objective: This study aimed at evaluating the role of "baseline" apparent diffusion coefficent (ADC), in patients affected by head and neck cancer treated with radio-chemotherapy, as a potential marker of response to therapy.

Methods: Fifty-seven patients underwent pretreatment ADC maps. Minimum, maximum, and medium ADC were computed.

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration.

Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNF, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration.

Prognostic value of relative cerebral blood volume in patients with recurrent glioblastoma multiforme treated with bevacizumab.

Background: The aim of this study was to assess whether the early monitoring of the effects of bevacizumab in patients with recurrent glioblastoma multiforme (GBM) using perfusional dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) before and after the beginning of antiangiogenic therapy is predictive of treatment response.

Methods: Thirteen patients with recurrent GBM underwent perfusion MRI with relative cerebral blood volume (rCBV) mapping before (T0) and after the beginning (T1) of bevacizumab treatment. Recurrence Regions of Interest (RoIs) were positioned on the enhancing component of tumoral tissue revealed by postcontrast T1-weighted images.

Antagonistic TNF receptor one-specific antibody (ATROSAB): receptor binding and in vitro bioactivity.

Background: Selective inhibition of TNFR1 signaling holds the potential to greatly reduce the pro-inflammatory activity of TNF, while leaving TNFR2 untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a humanized antagonistic anti-TNFR1 antibody developed for the treatment of inflammatory diseases.

Methodology/principal Findings: The epitope of ATROSAB resides in the N-terminal region of TNFR1 covering parts of CRD1 and CRD2.

MRI can assess glenoid bone loss after shoulder luxation: inter- and intra-individual comparison with CT.

Objective: Computed tomography (CT) is the gold standard for evaluating glenoid bone loss in patients with glenohumeral dislocations. The aim of this study was to verify if magnetic resonance imaging (MRI) can quantify the area of bone loss without any significant difference from CT.

Materials And Methods: Twenty-three patients, who had experienced one or more post-traumatic unilateral glenohumeral dislocations, underwent MRI and CT.

In vivo imaging of choroidal angiogenesis using fluorescence-labeled cationic liposomes.

Purpose: Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration (AMD) enables sensitive use of antiangiogenic drugs and reduces adverse side effects. So far, no in vivo imaging methods are available to specifically label active angiogenesis. Here, we report such a technique using fluorophore-labeled cationic liposomes (CL) detected with a standard clinical in vivo scanning laser ophthalmoscope (SLO).

Comparison of lung accumulation of cationic liposomes in normal rats and LPS-treated rats.

Objective: Cationic liposomes have been shown to target angiogenic endothelial cells in lungs and joints with evidence of chronic inflammation. We sought to determine whether cationic liposomes accumulate in acutely inflamed lung tissue. SUBJECTS, TREATMENT AND METHODS: Acute lung injury was induced by intratracheal instillation of lipopolysaccharide (LPS) in Sprague Dawley rats.

Vascular targeting by EndoTAG-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer.

Cationic lipid complexed paclitaxel (EndoTAG-1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG-1 therapy and analyze the impact of EndoTAG-1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG-1 in combination with conventional gemcitabine or cisplatin therapy was evaluated in L3.

Maternal HIV type 1 infection suppresses MMP-1 expression in endothelial cells of uninfected newborns: nonviral vertical transmission of HIV type 1-related effects.

HIV-1 infection is associated with vascular alterations. This is accompanied by an increased risk of cardiovascular diseases and Kaposi's sarcoma, an endothelial cell-derived tumor. We investigated the impact of maternal HIV-1 infection on phenotype and gene expression of endothelial cells in newborns.

EBV latent membrane protein-1 protects B cells from apoptosis by inhibition of BAX.

Latent membrane protein 1 (LMP-1) of Epstein-Barr virus (EBV) promotes tumorigenesis by inhibiting apoptosis. We show that an important antiapoptotic activity of LMP-1 is the inhibition of Bcl2-associated protein X (Bax), a potent proapoptotic protein. BAX expression was regulated by LMP-1 activation of nuclear factor kappaB (NF-kappaB) via the C-terminal activation region 1 (CTAR-1) and CTAR-2.