Developing PRISM: A Pragmatic Institutional Survey and Bench Marking Tool to Measure Digital Research Maturity of Cancer Centers.

Background:  Multicenter precision oncology real-world evidence requires a substantial long-term investment by hospitals to prepare their data and align on common Clinical Research processes and medical definitions. Our team has developed a self-assessment framework to support hospitals and hospital networks to measure their digital maturity and better plan and coordinate those investments. From that framework, we developed PRISM for Cancer Outcomes: PR: agmatic I: nstitutional S: urvey and benchM: arking.

Association between health-related quality-of-life results, outcomes of efficacy and drug approvals: a meta-research study of randomized phase III trials in oncology.

Background: Despite the interest from the scientific community and regulatory agencies, limited data are available on the association between health-related quality-of-life (QoL) results, outcome of efficacy and drug approvals.

Materials And Methods: We updated the previously published meta-research study of phase III clinical trials in patients with solid tumours treated with systemic treatments, published from 2012 to 2021 in 11 selected journals. For the present analysis, we focused on studies conducted in the advanced setting.

Gut and local microbiota in patients with cancer: increasing evidence and potential clinical applications.

In recent years, cancer research has highlighted the role of disrupted microbiota in carcinogenesis and cancer recurrence. However, microbiota may also interfere with drug metabolism, influencing the efficacy of cancer drugs, especially immunotherapy, and modulating the onset of adverse events. Intestinal micro-organisms can be altered by external factors, such as use of antibiotics, proton pump inhibitors treatment, lifestyle and the use of prebiotics or probiotics.

Analysis of the adequacy of control arms in oncology randomised clinical trials published between 2017 and 2021: a meta-research study.

Introduction: Randomised controlled trials (RCTs) are usually considered the highest level of evidence for clinical practice. Patients assigned to control arm in RCTs should always receive the best available treatments to protect participants while also allowing for proper interpretation and applicability of study results. Here we analysed RCTs published in oncology between 2017 and 2021 to describe the frequency of suboptimal control arms.

Second-line therapy in pancreatic ductal adenocarcinoma (PDAC) patients with germline BRCA1-2 pathogenic variants (gBRCA1-2pv).

Background: Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking.

Methods: Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected.

Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer.

Background: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB).

Methods: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion.

Subgroup analyses in randomized phase III trials of systemic treatments in patients with advanced solid tumours: a systematic review of trials published between 2017 and 2020.

Background: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer.

Methods: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020.

A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma.

Introduction: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM.

Methods: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

Background: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting.

Patients And Methods: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible.

Adoption of multiple primary endpoints in phase III trials of systemic treatments in patients with advanced solid tumours. A systematic review.

Background And Aim: Trial designs using multiple primary endpoints (MPEs) are increasing in phase III cancer trials. Our objectives were to describe the incidence of MPEs in recently published phase III trials testing systemic treatments in patients with advanced cancer; the main characteristics of trials adopting MPEs; the presence of mature results for all endpoints in the primary publication; consistency between results of each endpoint and authors' conclusions.

Methods: Articles of randomised phase III trials conducted in patients with advanced cancer, published between 2017 and 2020, were retrieved from PubMed.

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort.

Objective: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients.

A review of molecularly targeted therapy in biliary tract carcinoma: what is the next step?

Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials.

Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion.

Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium.

Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin.

Given their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and display extensive self-renewal capacity in sphere cultures. To determine the origin of these cells, we genetically mapped the fate of neural crest cells in face and trunk skin of mouse.

Lineage-specific requirements of beta-catenin in neural crest development.

Beta-catenin plays a pivotal role in cadherin-mediated cell adhesion. Moreover, it is a downstream signaling component of Wnt that controls multiple developmental processes such as cell proliferation, apoptosis, and fate decisions. To study the role of beta-catenin in neural crest development, we used the Cre/loxP system to ablate beta-catenin specifically in neural crest stem cells.

Sox10 haploinsufficiency affects maintenance of progenitor cells in a mouse model of Hirschsprung disease.

Hirschsprung disease, or congenital megacolon, is characterized by aganglionosis of the terminal bowel, which leads to intestinal obstruction and chronic constipation. Several genes involved in the disease have been identified. In particular, haploinsufficiency of SOX10, which encodes a transcription factor, results in megacolon, often in combination with other disorders.

The role of the Ets domain transcription factor Erm in modulating differentiation of neural crest stem cells.

The transcription factor Erm is a member of the Pea3 subfamily of Ets domain proteins that is expressed in multipotent neural crest cells, peripheral neurons, and satellite glia. A specific role of Erm during development has not yet been established. We addressed the function of Erm in neural crest development by forced expression of a dominant-negative form of Erm.

Cell-intrinsic and cell-extrinsic cues regulating lineage decisions in multipotent neural crest-derived progenitor cells.

Multipotent stem cells must generate various differentiated cell types in correct number and sequence during neural development. In the peripheral nervous system (PNS), this involves the formation of postmigratory progenitor cell types which maintain multipotency and are able to give rise to neural and non-neural cells in response to instructive growth factors. We propose that fate restrictions in such progenitor cells are controlled by the combinatorial interaction of different extracellular signals, including community effects in response to both neurogenic and gliogenic factors.

Survival and glial fate acquisition of neural crest cells are regulated by an interplay between the transcription factor Sox10 and extrinsic combinatorial signaling.

The transcription factor Sox10 is required for proper development of various neural crest-derived cell types. Several lineages including melanocytes, autonomic and enteric neurons, and all subtypes of peripheral glia are missing in mice homozygous for Sox10 mutations. Moreover, haploinsufficiency of Sox10 results in neural crest defects that cause Waardenburg/Hirschsprung disease in humans.

The Ets domain transcription factor Erm distinguishes rat satellite glia from Schwann cells and is regulated in satellite cells by neuregulin signaling.

Distinct glial cell types of the vertebrate peripheral nervous system (PNS) are derived from the neural crest. Here we show that the expression of the Ets domain transcription factor Erm distinguishes satellite glia from Schwann cells beginning early in rat PNS development. In developing dorsal root ganglia (DRG), Erm is present both in presumptive satellite glia and in neurons.

Embryonic gene expression resolved at the cellular level by fluorescence in situ hybridization.

Tyramide signal amplification has successfully been applied to enhance detection limits of both immunological reactions and in situ hybridization methods. The technique uses short-range deposition of activated tyramide mediated by horseradish peroxidase. We have adapted this method to fluorescence in situ hybridization on embryonic tissue sections using fluorophore-labeled tyramide.