LYVE-1 macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer.

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer.

Epigenetic regulation of gene expression is crucial to the determination of cell fate in development and differentiation, and the Polycomb (PcG) and Trithorax (TrxG) groups of proteins, acting antagonistically as complexes, play a major role in this regulation. Although originally identified in Drosophila, these complexes are conserved in evolution and the components are well defined in mammals. Each complex contains a protein with methylase activity (KMT), which can add methyl groups to a specific lysine in histone tails, histone 3 lysine 27 (H3K27), by PcG complexes, and H3K4 and H3K36 by TrxG complexes, creating transcriptionally repressive or active marks, respectively.

Apoptosis in the Pancreatic Cancer Tumor Microenvironment-The Double-Edged Sword of Cancer-Associated Fibroblasts.

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. This is attributed to the disease already being advanced at presentation and having a particularly aggressive tumor biology. The PDAC tumor microenvironment (TME) is characterized by a dense desmoplastic stroma, dominated by cancer-associated fibroblasts (CAF), extracellular matrix (ECM) and immune cells displaying immunosuppressive phenotypes.

Social network analysis and whole-genome sequencing to evaluate disease transmission in a large, dynamic population: A study of avian mycobacteriosis in zoo birds.

This study combined a social network analysis and whole-genome sequencing (WGS) to test for general patterns of contagious spread of a mycobacterial infection for which pathways of disease acquisition are not well understood. Our population included 275 cases diagnosed with avian mycobacteriosis that were nested in a source population of 16,430 birds at San Diego Zoo Wildlife Alliance facilities from 1992 through mid-2014. Mycobacteria species were determined using conventional methods and whole genome sequencing (WGS).

Validation of the responding to urgency of need in palliative care (RUN-PC) triage tool.

Background: The Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool is a novel, evidence-based tool by which specialist palliative care services can manage waiting lists and workflow by prioritising access to care for those patients with the most pressing needs in an equitable, efficient and transparent manner.

Aim: This study aimed to establish the intra- and inter-rater reliability, and convergent validity of the RUN-PC Triage Tool and generate recommended response times.

Design: An online survey of palliative care intake officers applying the RUN-PC Triage Tool to a series of 49 real clinical vignettes was assessed against a reference standard: a postal survey of expert palliative care clinicians ranking the same vignettes in order of urgency.

Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype.

The tumour microenvironment plays a crucial role in the growth and progression of cancer, and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies have demonstrated that TAMs display transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype that to the best of our knowledge has not previously been described.

O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR.

Aberrant mucin-type O-linked glycosylation is a common occurrence in cancer where the upregulation of sialyltransferases is often seen leading to the early termination of O-glycan chains. Mucin-type O-linked glycosylation is not limited to mucins and occurs on many cell surface glycoproteins including EGFR, where the number of sites can be limited. Upon EGF ligation, EGFR induces a signaling cascade and may also translocate to the nucleus where it directly regulates gene transcription, a process modulated by Galectin-3 and MUC1 in some cancers.

Mucins and their receptors in chronic lung disease.

There is growing recognition that mucus and mucin biology have a considerable impact on respiratory health, and subsequent global morbidity and mortality. Mucins play a critical role in chronic lung disease, not only by providing a physical barrier and clearing pathogens, but also in immune homeostasis. The aim of this review is to familiarise the reader with the role of mucins in both lung health and disease, with particular focus on function in immunity, infection and inflammation.

Describing the psychosocial profile and unmet support needs of parents caring for a child with a life-limiting condition: A cross-sectional study of caregiver-reported outcomes.

Background: There is a lack of studies examining the prevalence and severity of psychosocial distress in parents caring for a child with life-limiting condition. More research is also needed to better understand the experience, support needs and quality-of-life of this population.

Aim: To describe the experience and support needs of caring for children with life-limiting conditions and examine the level of distress and quality-of-life experienced by parents.

Triaging the Terminally Ill-Development of the Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool.

Context: Evidence-based resource allocation is receiving increasing attention as we strive for equity, transparency, and cost-effectiveness across health care. In the context of finite resources, which of our patients with terminal illness should be prioritized for urgent palliative care?

Objectives: To develop the scoring system for the novel Responding to Urgency of Need in Palliative Care triage tool.

Methods: Online international discrete choice experiment involving palliative care clinicians to establish the relative importance of seven key attributes of palliative care triage identified during an earlier qualitative study.

The first reptilian circovirus identified infects gut and liver tissues of black-headed pythons.

Viral metagenomic analysis of the liver of a black headed python (Aspidites melanocephalus) euthanized for a proliferative spinal lesion of unknown etiology yielded the first characterized genome of a reptile-infecting circovirus (black-headed python circovirus or BhPyCV). BhPyCV-specific in situ hybridization (ISH) showed that viral nucleic acids were strongly expressed in the intestinal lining and mucosa and multifocally in the liver. To investigate the presence of this virus in other snakes and its possible pathogenicity, 17 snakes in the python family with spinal disease were screened with ISH yielding a second BhP positive in intestinal tissue, and a Boelen's python (Morelia boeleni) positive in the liver.

Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis.

Objective: We sought to develop the first Damage Index (DI) in systemic sclerosis (SSc).

Methods: The conceptual definition of 'damage' in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI.

Novel application of discrete choice experiment methodology to understand how clinicians around the world triage palliative care needs: A research protocol.

Objective: As referrals to specialist palliative care (PC) grow in volume and diversity, an evidence-based triage method is needed to enable services to manage waiting lists in a transparent, efficient, and equitable manner. Discrete choice experiments (DCEs) have not to date been used among PC clinicians, but may serve as a rigorous and efficient method to explore and inform the complex decision-making involved in PC triage. This article presents the protocol for a novel application of an international DCE as part of a mixed-method research program, ultimately aiming to develop a clinical decision-making tool for PC triage.

The trajectory of patients who die from metastatic prostate cancer: a population-based study.

Objectives: To describe health service use, symptom and survival characteristics in metastatic prostate cancer (mPCa) in order to outline usual care practices and identify future opportunities to improve the quality of care in this patient group.

Patients And Methods: This population cohort study, conducted in Victoria, Australia, used 10 years (2000-2010) of linked hospital discharge, emergency visit, and death registration data, to track patients from their first inpatient admission with mPCa until death. Descriptive statistics on inpatient health service use, symptoms, procedures, survival, and place of death are presented.

Patient-reported outcome measures and their utility in the management of patients with advanced chronic kidney disease.

Symptom and quality of life (QOL) measures in patients with advanced chronic kidney disease are recognized indicators of patient-centred care and represent important research, quality and clinical measures. This study examined relationships between symptom burden, QOL and functional status and associations of symptoms and mortality risk. A multisite longitudinal cohort analysis was undertaken in chronic kidney disease stage 4/5 (no dialysis) and dialysis patients.

Responding to urgency of need: Initial qualitative stage in the development of a triage tool for use in palliative care services.

Background: Palliative care services face the challenge of a workload increasing in volume and diversity. An evidence-based triage method to assess urgency of palliative care needs is required to ensure equitable, efficient and transparent allocation of specialist resources when managing waiting lists.

Aim: As the initial stage of a mixed-method sequential design, this study aimed to explore palliative care providers' practices and attitudes towards triaging palliative care needs and their views regarding the implementation of a standardised approach.

O-linked mucin-type glycosylation in breast cancer.

Changes in mucin-type O-linked glycosylation are seen in over 90% of breast cancers where increased sialylation is often observed and a change from branched glycans to linear glycans is often seen. There are many mechanisms involved including increased/altered expression of glycosyltransferases and relocalisation to the endoplasmic reticulum of the enzymes responsible for the addition of the first sugar, -acetyl-d-galactosamine. It is now becoming clear that these changes can contribute to tumour growth and progression by modulating the micro-environment through glycan-sensing lectins expressed on immune cells, by modulating interactions with tumour surface receptors and by binding to selectins.

Latest developments in MUC1 immunotherapy.

Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma.

Tn and STn are members of a family of carbohydrate tumor antigens that possess carbohydrate-carbohydrate interactions.

The mucin-type O-glycome in cancer aberrantly expresses the truncated glycans Tn (GalNAcα1-Ser/Thr) and STn (Neu5Acα2,6GalNAcα1-Ser/Thr). However, the role of Tn and STn in cancer and other diseases is not well understood. Our recent discovery of the self-binding properties (carbohydrate-carbohydrate interactions, CCIs) of Tn (Tn-Tn) and STn (STn-STn) provides a model for their possible roles in cellular transformation.

Transition Points for the Routine Integration of Palliative Care in Patients With Advanced Cancer.

Context: Increasing emphases are being placed on early integration of palliative care for patients with advanced cancers, yet barriers to implementation in clinical practice remain. Criteria to standardize referral have been endorsed, but their application is yet to be tested at the population level.

Objectives: This study sought to establish the need for standardized referral by examining current end-of-life care outcomes of decedents with cancer and define transition points within a cancer illness course, which are associated with poor prognosis, whereby palliative care should be routinely introduced to augment clinician-based decision making.

Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic Efficacy in Preclinical Models of Cancer.

Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immunosuppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited antitumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinemia, as an immune checkpoint blockade therapy for the treatment of cancer.