Cerebrovascular Reactivity Mapping in Brain Tumors Based on a Breath-Hold Task Using Arterial Spin Labeling.

Hemodynamic measurements such as cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) can provide useful information for the diagnosis and characterization of brain tumors. Previous work showed that arterial spin labeling (ASL) in combination with vasoactive stimulation enabled simultaneous non-invasive evaluation of both parameters, however this approach had not been previously tested in tumors. The aim of this work was to investigate the application of this technique, using a pseudo-continuous ASL (PCASL) sequence combined with breath-holding at 3 T, to measure CBF and CVR in high-grade gliomas and metastatic lesions, and to explore differences across tumoral-peritumoral regions and tumor types.

Presence of Activated (Phosphorylated) STAT3 in Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases.

Brain radiation necrosis (RN) is a subacute or late adverse event following radiotherapy, involving an exacerbated inflammatory response of the brain tissue. The risk of symptomatic RN associated with stereotactic radiosurgery (SRS) as part of the treatment of brain metastases (BMs) has been a subject of recent investigation. The activation of the signal transducer and activator of transcription 3 (STAT3) was shown in reactive astrocytes (RA) associated with BMs.

Targeting the extra domain A of fibronectin for cancer therapy with CAR-T cells.

Background: One of the main difficulties of adoptive cell therapies with chimeric antigen receptor (CAR)-T cells in solid tumors is the identification of specific target antigens. The tumor microenvironment can present suitable antigens for CAR design, even though they are not expressed by the tumor cells. We have generated a CAR specific for the splice variant extra domain A (EDA) of fibronectin, which is highly expressed in the tumor stroma of many types of tumors but not in healthy tissues.

Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19.

Background: Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but have also been shown to mediate tissue damage in a number of diseases.

Heterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8.

Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models.

PD-L1 in Cytological Samples: A Review and a Practical Approach.

With a growing number of predictive biomarkers needed to manage patients with non-small cell lung cancer (NSCLC), there has been a paradigm shift in care and handling of diagnostic samples. Among the various testing methods, immunohistochemistry (IHC) is the most cost- effective and widely available. Furthermore, over the past decade immunotherapy has emerged as one of the most promising cancer treatments.

Utilisation of cytological samples for multiplex immunofluorescence assay.

Objective: Understanding the immune environment of non-small cell lung cancer (NSCLC) is important for designing effective anticancer immunotherapies. We describe the use of multiplex immunofluorescence (mIF) assays to enable characterisation of the tumour-infiltrating immune cells and their interactions, both across and within immune subtypes.

Methods: Six cytological samples of NSCLC taken by transoesophageal ultrasound-guided fine needle aspiration were tested with an mIF assay designed to detect the expression of key immune cell markers such as CD3, CD8, CD20, CD11b, and CD68.

A comprehensive diagnosis of a desmoplastic small round cell tumor of unusual location based on fine-needle aspiration cytology: Report of a case arising in the parotid gland and review of the literature.

Desmoplastic small round cell tumor (DSRCT) is rare and a highly aggressive neoplasm that typically involves the soft tissues of the abdomen or pelvis in children or young adults, showing a male predilection. Although it can occurs over a wide age range, the peak incidence is in the third decade of life. DSRCT usually shows widespread abdominal serosal involvement, and overall patient survival is poor.

Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence.

The precise nature of the local immune responses in lung tuberculosis (TB) granulomas requires a comprehensive understanding of their environmental complexities. At its most basic level, a granuloma is a compact, organized immune aggregate of macrophages surrounded by myeloid, B and T cells. We established two complementary multiplex immunolabeling panels to simultaneously evaluate the myeloid and lymphocytic contexture of 14 human lung TB granulomas in formalin-fixed paraffin-embedded tissue samples.

Programmed death-ligand 1 expression on direct Pap-stained cytology smears from non-small cell lung cancer: Comparison with cell blocks and surgical resection specimens.

Background: Programmed death-ligand 1 (PD-L1) expression, as assessed by immunohistochemistry (IHC), is used to select patients with non-small cell lung cancer (NSCLC) for anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. The current study evaluated the feasibility and efficacy of PD-L1 immunostaining and quantitation on direct Papanicolaou-stained cytological smears compared with formalin-fixed paraffin-embedded samples (cytological cell blocks and surgical resection specimens) in NSCLC cases using 2 commercially available assays: the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies/Dako, Carpinteria, CA, USA) and the Ventana SP263 Assay (Ventana Medical Systems Inc, Tucson, Arizona).

Methods: PD-L1 immunostaining using either both or one of the assays was tested in 117 sets of paired samples obtained from 62 NSCLC cases.

Identification of mutations associated with acquired resistance to sunitinib in renal cell cancer.

Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC.

Metastatic tumors in the pancreas: the role of endoscopic ultrasound-guided fine-needle aspiration.

Background And Objectives: there are few published data on the use of EUS guided fine-needle aspiration in secondary pancreatic lesions. We describe the largest series published so far in a European country.

Patients And Methods: a retrospective review of the cases identified in our institution from 2004 to 2016 has been recorded.

Mechanical barriers and transforming growth factor beta inhibitor on epidural fibrosis in a rabbit laminectomy model.

Background: TGF-β has been described as a mediator of fibrosis and scarring. Several studies achieved reduction in experimental scarring through the inhibition of TGF-β. Fibroblasts have been defined as the cell population originating fibrosis, blocking fibroblast invasion may impair epidural fibrosis appearance.

Cytology Smears in the Era of Molecular Biomarkers in Non-Small Cell Lung Cancer: Doing More With Less.

Context: - The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used.

Immune mediated colitis caused by lung cancer treatment with atezolizumab.

Atezolizumab is an IgG1 isotype monoclonal antibody against the protein programmed cell death-ligand 1 (PD- L1). PD-L1 may be highly expressed in some tumors and is believed to inhibit immune cells that recognize and attack tumor cells. Inhibition of PD-L1 can remove its inhibitory effect and provoke an anti-tumor response.

White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.

Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. We look for WM tract voxel clusters showing significant differences when comparing of AD vs.

Functional expression of CD137 (4-1BB) on T helper follicular cells.

CD137 (4-1BB) is a surface protein initially discovered to mark activated T lymphocytes. However, its broader expression pattern also encompasses activated NK cells, B cells and myeloid cells, including mature dendritic cells. In this study, we have immunostained for CD137 on paraffin-embedded lymphoid tissues including tonsils, lymph nodes, ectopic tertiary lymphoid tissue in Hashimoto thyroiditis and cancer.

Eigenanatomy on Fractional Anisotropy Imaging Provides White Matter Anatomical Features Discriminating Between Alzheimer's Disease and Late Onset Bipolar Disorder.

Background: Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging.

Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis.

Objectives: Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes.

Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators.

Background: Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome.

Methods: Primary tumour tissue from 485 patients, surgically treated for stage I-II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR).

Lung cancer screening: fourteen year experience of the Pamplona early detection program (P-IELCAP).

Introduction And Objectives: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain.

Assessment of EGFR and KRAS mutation status from FNAs and core-needle biopsies of non-small cell lung cancer.

Background: Molecular testing to determine gene mutation status is now the recommended standard of care for patients with advanced or metastatic Non-small cell lung cancer (NSCLC). Because the majority of patients with NSCLC present with metastatic disease, minimally invasive procedures are necessary for diagnosis, staging, and molecular analysis. However, the resulting samples have perceived limitations in the oncology community, and most commercially available tests have not been validated for these sample types.