The use of a multi-metric readout screen to identify EHMT2/G9a-inhibition as a modulator of cancer-associated fibroblast activation state.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression, including mediating tumour cell invasion via their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM). Given that reduced CAF abundance in tumours correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in regions of tumour-stromal mixing with the goal of reducing tumour aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) platform, we performed an image-based, phenotypic screen that enabled us to identify modulators of CAF abundance and the capacity of CAFs to induce tumour cell invasion.

Single-Cell Analysis Reveals Transcriptomic Features of Drug-Tolerant Persisters and Stromal Adaptation in a Patient-Derived EGFR-Mutated Lung Adenocarcinoma Xenograft Model.

Introduction: Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is mainly driven by minor subpopulations of drug-tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted with cell line models.

Guided Self-Assembly of ES-Derived Lung Progenitors into Biomimetic Tube Structures That Impact Cell Differentiation.

Chemically directed differentiation of pluripotent stem cells (PSCs) into defined cell types is a potent strategy for creating regenerative tissue models and cell therapies. In vitro observations suggest that physical cues can augment directed differentiation. We recently demonstrated that confining human PSC-derived lung progenitor cells in a tube with a diameter that mimics those observed during lung development results in the alteration of cell differentiation towards SOX2SOX9 lung cells.

Compassionate use of anti-IL6 receptor antibodies in critically ill patients with acute respiratory distress syndrome due to SARS-CoV-2.

Background: COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19.

Patient-derived cell line, xenograft and organoid models in lung cancer therapy.

Lung cancer accounts for most cancer-related deaths worldwide and has an overall 5-year survival rate of ~15%. Cell lines have played important roles in the study of cancer biology and potential therapeutic targets, as well as pre-clinical testing of novel drugs. However, most experimental therapies that have cleared preclinical testing using established cell lines have failed phase III clinical trials.

Assembly of lung progenitors into developmentally-inspired geometry drives differentiation via cellular tension.

During organogenesis groups of differentiating cells self-organize into a series of structural intermediates with defined architectural forms. Evidence is emerging that such architectural forms are important in guiding cell fate, yet in vitro methods to guide cell fate have focused primarily on un-patterned exposure of stems cells to developmentally relevant chemical cues. We set out to ask if organizing differentiating lung progenitors into developmentally relevant structures could be used to influence differentiation status.

Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A tissue model to probe tumour phenotypes at tumour-stroma interfaces.

The interface between a tumour and the adjacent stroma is a site of great importance for tumour development. At this site, carcinoma cells are highly proliferative, undergo invasive phenotypic changes, and directly interact with surrounding stromal cells, such as cancer-associated fibroblasts (CAFs) which further exert pro-tumorigenic effects. Here we describe the development of GLAnCE (Gels for Live Analysis of Compartmentalized Environments), an easy-to-use hydrogel-culture platform for investigating CAF-tumour cell interaction dynamics in vitro at a tumour-stroma interface.

A TRACER 3D Co-Culture tumour model for head and neck cancer.

Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment and have been shown to play an important role in the progression of cancer. To probe these tumour-stroma interactions, we incorporated CAFs derived from head and neck cancer patients and squamous carcinoma cells of the hypopharynx (FaDu) into the Tissue Roll for the Analysis of Cellular Environment and Response (TRACER) platform to establish a co-culture platform that simulates the CAF-tumour microenvironmental interactions in head and neck tumours. TRACER culture involves infiltrating cells into a thin fibrous scaffold and then rolling the resulting biocomposite around a mandrel to generate a 3D and layered structure.

The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are Accessible for Drug Discovery?

Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted.

Modulation of cellular polarization and migration by ephrin/Eph signal-mediated boundary formation.

Compartment boundaries are essential for ensuring proper cell organization during embryo development and in adult tissues, yet the mechanisms underlying boundary establishment are not completely understood. A number of mechanisms, including (i) differential adhesion, (ii) differential tension, and (iii) cell signaling-mediated cell repulsion, are known to contribute and likely a context-dependent balance of each of these dictates boundary implementation. The ephrin/Eph signaling pathway is known to impact boundary formation in higher animals.

Correction: Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration.

Correction for 'Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration' by Michael Woolman et al., Analyst, 2017, 142, 3250-3260.

Rapid determination of the tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration.

Squamous cell carcinomas constitute a major class of head & neck cancers, where the tumour stroma ratio (TSR) carries prognostic information. Patients affected by stroma-rich tumours exhibit a poor prognosis and a higher chance of relapse. As such, there is a need for a technology platform that allows rapid determination of the tumour stroma ratio.

Hemoglobin levels and circulating blasts are two easily evaluable diagnostic parameters highly predictive of leukemic transformation in primary myelofibrosis.

To predict leukemic transformation (LT), we evaluated easily detectable diagnostic parameters in 338 patients with primary myelofibrosis (PMF) followed in the Latium region (Italy) between 1981 and 2010. Forty patients (11.8%) progressed to leukemia, with a resulting 10-year leukemia-free survival (LFS) rates of 72%.

An in vitro model of tissue boundary formation for dissecting the contribution of different boundary forming mechanisms.

During development and in adult tissues separation of phenotypically distinct cell populations is necessary to ensure proper organization and function of tissues and organs. Various phenomena, such as differential adhesion, differential mechanical tension and cell-cell repulsion, are proposed to cause boundary formation. Moreover, emerging evidence suggests that interplay between multiple such phenomena can underlie boundary formation.

Micropatterning strategies to engineer controlled cell and tissue architecture in vitro.

Micropatterning strategies, which enable control over cell and tissue architecture in vitro, have emerged as powerful platforms for modelling tissue microenvironments at different scales and complexities. Here, we provide an overview of popular micropatterning techniques, along with detailed descriptions, to guide new users through the decision making process of which micropatterning procedure to use, and how to best obtain desired tissue patterns. Example techniques and the types of biological observations that can be made are provided from the literature.

Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients.

Background: The correlation between obesity and severity of obstructive sleep apnea (OSA) is controversial. Although fat excess is a predisposing factor for the development of OSA, it has not been determined whether fat distribution rather than obesity per se is associated with OSA severity. Epicardial fat thickness (EFT) is an independent index of visceral adiposity and cardiometabolic risk.

Supracricoid partial laryngectomy in the treatment of laryngeal cancer: univariate and multivariate analysis of prognostic factors.

Objectives: To evaluate the oncological results of supracricoid partial laryngectomy as a treatment for selected glottic and supraglottic cancer in a large series of patients who had undergone uniform treatment over a 16-year period and to determine the different prognostic factors that may influence local control and survival.

Design: Retrospective clinical study.

Setting: Academic tertiary referral medical center.

The influence of lifestyle on cardiovascular risk factors. Analysis using a neural network.

The cardiovascular pathologies are the most common causes of death in the elderly patient. To single out the main risk factors in order to effectively prevent the onset of the disease, the authors experimented a special computerized tool, the neural network, that works out a mathematical relation that can obtain certain data (defined as output) as a function of other data (defined as input). Data were processed from a sample of 276 subjects of both sexes aged 26-69 years old.

Prognostic value of resection margins in supracricoid laryngectomy.

Objectives: The objective was to assess the prognostic value of surgical margin involvement in patients treated for squamous cell carcinoma of the larynx.

Study Design: Retrospective study.

Methods: A review was made of 253 patients treated with supracricoid laryngectomy between 1984 and 2001.

Decreased habituation of the R2 component of the blink reflex in migraine patients.

Objective: Activation of the trigemino-vascular system as well as of brainstem trigeminal nuclei are thought to play an important role in migraine. The aim of this study was to investigate the habituation phenomenon of the blink reflex in 30 headache-free migraine patients and 30 control subjects.

Methods: An electromyographic device with a specific habituation test program was used to elicit and record blink reflex responses on both the right and left sides, and to randomly repeat the stimulations at different time intervals in order to induce habituation.

Acute nonlymphocytic leukemia: onset after treatment for Hodgkin's disease.

This study was undertaken to examine the influence of various factors on the occurrence of acute nonlymphocytic leukemia (ANLL) in a group of longterm survivors of Hodgkin's disease (HD). From 1972 to 1992, 1045 patients with HD were assessed and treated at the Department of Radiation Oncology, the Institute of Radiology, and the Department of Human Biopathology, Hematology Section, University of Rome "La Sapienza". The average follow-up was 72 months.

Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias.

We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months.

Circadian variations of epithelial cell proliferation in human rectal crypts.

Background/aims: Evidence (almost exclusively from animal studies) suggests that proliferation within the colorectal mucosa undergoes circadian variations. The epithelial cells that line the human colorectal crypt occupy definite positions along the longitudinal axis according to their proliferative potential and degree of differentiation. Thus, circadian rhythmicity was investigated in humans to locate the areas along the longitudinal crypt axis in which diurnal fluctuation might occur.

Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group.

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%).