Moving Forward on Tumor Pathology Research Reporting: A Guide for Pathologists From the World Health Organization Classification of Tumors Living Evidence Gap Map by Tumour Type Group.

Evidence-based medicine (EBM) can be an unfamiliar territory for those working in tumor pathology research, and there is a great deal of uncertainty about how to undertake an EBM approach to planning and reporting histopathology-based studies. In this article, reviewed and endorsed by the Word Health Organization International Agency for Research on Cancer's International Collaboration for Cancer Classification and Research, we aim to help pathologists and researchers understand the basics of planning an evidence-based tumor pathology research study, as well as our recommendations on how to report the findings from these. We introduce some basic EBM concepts, a framework for research questions, and thoughts on study design and emphasize the concept of reporting standards.

A New Hierarchy of Research Evidence for Tumor Pathology: A Delphi Study to Define Levels of Evidence in Tumor Pathology.

The hierarchy of evidence is a fundamental concept in evidence-based medicine, but existing models can be challenging to apply in laboratory-based health care disciplines, such as pathology, where the types of evidence and contexts are significantly different from interventional medicine. This project aimed to define a comprehensive and complementary framework of new levels of evidence for evaluating research in tumor pathology-introducing a novel Hierarchy of Research Evidence for Tumor Pathology collaboratively designed by pathologists with help from epidemiologists, public health professionals, oncologists, and scientists, specifically tailored for use by pathologists-and to aid in the production of the World Health Organization Classification of Tumors (WCT) evidence gap maps. To achieve this, we adopted a modified Delphi approach, encompassing iterative online surveys, expert oversight, and external peer review, to establish the criteria for evidence in tumor pathology, determine the optimal structure for the new hierarchy, and ascertain the levels of confidence for each type of evidence.

The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment.

Background: A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression.

Understanding the use of evidence in the WHO Classification of Tumours: a protocol for an evidence gap map of the classification of tumours of the lung.

Introduction: There are gaps in the evidence base of tumour classification despite being essential for cancer diagnosis, treatment and patient care. The WHO in charge of the production of an updated international classification, the WHO Classification of Tumours (WCT), aims to adapt evidence gap map (EGM) methodology to inform future editions of the WCT, by providing a visual summary of the existing evidence.

Methods And Analysis: Bibliographical references used in the WCT fifth edition of Tumours of the Lung (Thoracic Tumours volume) will be used as search results of a literature search.

Beneficial effects of β-escin on muscle regeneration in rat model of skeletal muscle injury.

Background: Recent advancements in understanding β-escin action provide basis for new therapeutic claims for the drug. β-escin-evoked attenuation of NF-κB-dependent signaling, increase in MMP-14 and decrease in COUP-TFII content and a rise in cholesterol biosynthesis could be beneficial in alleviating muscle-damaging processes.

Purpose: The aim of this study was to investigate the effect of β-escin on skeletal muscle regeneration.

Circulating Hsa-miR-431-5p as Potential Biomarker for Squamous Cell Vulvar Carcinoma and Its Premalignant Lesions.

Vulvar squamous cell carcinoma (VSCC) develops from high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN). This study aimed to assess the diagnostic value of circulating hsa-miR-431-5p in vulvar precancers and VSCC. Expression levels of hsa-miR-431-5p were analyzed by quantitative RT-PCR in plasma samples of 29 patients with vulvar precancers (HSIL or dVIN), 107 with VSCC as well as 15 healthy blood donors.

CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma.

Aims: Vulvar squamous cell carcinoma (VSCC) spreads early and mainly locally direct expansion into adjacent structures, followed by lymphatic metastasis to the regional lymph nodes (LNs). In the lymphatic metastasis, cancer cells bearing CXCR4 and ACKR3 (CXCR7) receptors are recruited to the LNs that produce the CXCL12 ligand. Our study aimed to assess the role of the CXCR4/ACKR3/CXCL12 axis in VSCC progression.

Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression.

Current knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors that would permit to stratify patients by progression risk. Early-stage tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics.

Photoperiod Affects Leptin Action on the Choroid Plexus in Ewes Challenged with Lipopolysaccharide-Study on the mRNA Level.

The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (), proinflammatory cytokines (, ), their receptors (, , , , ) and inflammasome components necessary for pro-IL-1β activation (, , ), chemokine (), leptin receptor isoforms (, ) and a suppressor of cytokine signalling () in the ChP of ewes treated or not with lipopolysaccharide (LPS).

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma.

Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development.

Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies.

In this review, we summarize the existing literature on next generation sequencing (NGS) studies in vulvar squamous cell carcinoma (VSCC). A total of 201 VSCC tumor samples were investigated in five studies published between 2017 and 2019. Findings on somatic mutations in human papillomavirus (HPV)-DNA positive (HPV+) and HPV-DNA negative (HPV-) disease were extracted and submitted to pathway and drug candidate analyses.

The anti-inflammatory potential of cefazolin as common gamma chain cytokine inhibitor.

A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.

Melatonin from slow-release implants upregulates claudin-2 in the ovine choroid plexus.

In ewes, the turnover rate of cerebrospinal fluid (CSF), mainly produced by choroid plexus (ChP), is photoperiodically modulated and is higher during short days (SDs) than long days (LDs). We demonstrated that, melatonin from continuous slow-release implants increases the expression of aquaporins, water channel-forming proteins engaged in transcellular water transport (across the plasma membrane of the cells), in the ovine ChP. This study evaluated the effect of slow-release melatonin implants on the expression of claudin-2 (CLDN2), a pore-forming protein that allows the paracellular passage (between the cells) of select inorganic cations and water, in the ovine ChP.

Neostigmine Attenuates Proinflammatory Cytokine Expression in Preoptic Area but Not Choroid Plexus during Lipopolysaccharide-Induced Systemic Inflammation.

The study was designed to examine whether the administration of neostigmine (0.5 mg/animal), a peripheral inhibitor of acetylcholinesterase (AChE), during an immune/inflammatory challenge provoked by intravenous injection of bacterial endotoxin-lipopolysaccharide (LPS; 400 ng/kg)-attenuates the synthesis of proinflammatory cytokines in the ovine preoptic area (POA), the hypothalamic structure playing an essential role in the control of the reproduction process, and in the choroid plexus (CP), a multifunctional organ sited at the interface between the blood and cerebrospinal fluid in the ewe. Neostigmine suppressed ( < 0.

Somatic mutation profiling of vulvar cancer: Exploring therapeutic targets.

Background: Vulvar squamous cell carcinoma (VSCC) constitutes over 90% of vulvar cancer. Its pathogenesis can follow two different pathways; high risk human papillomavirus (hrHPV)-dependent and HPV-independent. Due to the rarity of VSCC, molecular mechanisms underlying VSCC development remain largely unknown.

Technetium-99m-based Radiopharmaceuticals in Sentinel Lymph Node Biopsy: Gynecologic Oncology Perspective.

Technetium (99mTc)-radiolabeled colloids are popular tracers used to map lymphatic vessels and regional lymph nodes (LNs). The regional LN status is a significant determinant of cancer stage and patient prognosis, and strongly influences treatment. Regional LN dissection has become a part of surgical treatment.

Normalizers for microRNA quantification in plasma of patients with vulvar intraepithelial neoplasia lesions and vulvar carcinoma.

The role of circulating microRNAs as a promising tool for diagnosing cancer and monitoring anticancer therapies has been widely studied in the past decades. To date, no suitable reference microRNAs for normalizing quantitative real-time polymerase chain reaction assays has been identified in vulvar intraepithelial neoplasia lesions and vulvar squamous cell carcinoma. The purpose of this study was to select appropriate references for gene expression studies in plasma of patients with these lesions.

BCOR Internal Tandem Duplication in High-grade Uterine Sarcomas.

Endometrial stromal sarcomas (ESSs) are mesenchymal uterine tumors characterized by recurrent genetic events, most commonly chromosomal rearrangements, that create oncogenic gene fusions. High-grade endometrial stromal sarcomas (HG-ESSs), as defined in the 2014 World Health Organization Classification, typically contain oncogenic YWHAE-NUTM2 fusions; however, although not well characterized, there are tumors morphologically overlapping with HG-ESS that do not contain the YWHAE-NUTM2 fusions. These fusions are also found in certain pediatric primitive sarcomas, including clear cell sarcoma of the kidney and soft tissue undifferentiated round cell sarcoma of infancy.

Interleukin 1β polymorphism and serum level are associated with pediatric asthma.

Background And Aim: Interleukin-1 is a pro-inflammatory cytokine found in two forms (α and β). The α form is mainly cell-bound, whereas IL-1β is primarily secreted by macrophages in response to immune system stimulation. We hypothesized that polymorphic variants of interleukin 1 genes may play a role in childhood asthma risk.

Plasma and cerebrospinal fluid interleukin-1β during lipopolysaccharide-induced systemic inflammation in ewes implanted or not with slow-release melatonin.

Background: Interleukin-1β (IL-1β) is important mediator of inflammatory-induced suppression of reproductive axis at the hypothalamic level. At the beginning of inflammation, the main source of cytokines in the cerebrospinal fluid (CSF) is peripheral circulation, while over time, cytokines produced in the brain are more important. Melatonin has been shown to decrease pro-inflammatory cytokines concentration in the brain.

The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes.

The present study concerns the effect of melatonin from slow-release implants on the expression of genes coding interleukin-1β (Il1B), inerleukin-6 (Il6), tumour necrosis factor α (Tnf) and their receptors: IL-1 receptor type I (Il1r1) and type II (Il1r2), IL-6 receptor (Il6r) and signal transducer (Il6st), TNFα receptor type I (Tnfrsf1a) and II (Tnfrsf1b) and retinoid-related orphan receptor α (RorA) and Rev.-erbα in the ovine choroid plexus (CP) under basal and lipopolysaccharide (LPS)-challenged conditions. Studies were performed on four groups: 1) sham-implanted and placebo-treated, 2) melatonin-implanted (Melovine, 18mg) and placebo-treated, 3) sham-implanted and LPS-treated (400ng/kg of body weight) and 4) melatonin-implanted and LPS-treated.

Macrophage infiltration and genetic landscape of undifferentiated uterine sarcomas.

Endometrial stromal tumors include translocation-associated low- and high-grade endometrial stromal sarcomas (ESS) and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of aggressive tumors and is often seen as a diagnosis of exclusion after ESS and leiomyosarcoma (LMS) have been ruled out. We performed a comprehensive analysis of gene expression, copy number variation, point mutations, and immune cell infiltrates in the largest series to date of all major types of uterine sarcomas to shed light on the biology of UUS and to identify potential novel therapeutic targets.

Pharmacophore guided discovery of small-molecule interleukin 15 inhibitors.

Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases.

Current approaches for avoiding the limitations of circulating tumor cells detection methods-implications for diagnosis and treatment of patients with solid tumors.

Eight million people die of cancer each year and 90% of deaths are caused by systemic disease. Circulating tumor cells (CTCs) contribute to the formation of metastases and thus are the subject of extensive research and an abiding interest to biotechnology and pharmaceutical companies. Recent technological advances have resulted in greatly improved CTC detection, enumeration, expansion, and culture methods.