Generation of Devil Facial Tumour Cells Co-Expressing MHC With CD80, CD86 or 41BBL to Enhance Tumour Immunogenicity.

The major histocompatibility complex (MHC) molecules play an integral role in the adaptive immune response to transmissible cancers through tumour antigen presentation and recognition of allogeneic MHC molecules. The transmissible devil facial tumours 1 and 2 (DFT1 and DFT2) modulate MHC-I antigen presentation to evade host immune responses and facilitate transmission of tumours cells to new Tasmanian devil (Sarcophilus harrisii) hosts. To enhance T-cell-driven tumour immunogenicity for vaccination and immunotherapy, DFT1 and DFT2 cells were co-transfected with (i) NLRC5 for MHC-I expression or CIITA for MHC-I and MHC-II expression, and (ii) a co-stimulatory molecule, either CD80, CD86 or 41BBL.

Assessing the clinical utility of toxicology testing in the peripartum period.

Background: Toxicology testing is frequently used as a means of gathering objective data about substance use in pregnancy, but little is known about the clinical utility of testing in the peripartum setting.

Objective: This study aimed to characterize the utility of obtaining maternal-neonatal dyad toxicology testing at the time of delivery.

Study Design: We performed a retrospective chart review of all deliveries in a single healthcare system in Massachusetts between 2016 and 2020, and identified deliveries with either maternal or neonatal toxicology testing at delivery.

Early Cancer Biomarker Discovery Using DIA-MS Proteomic Analysis of EVs from Peripheral Blood.

One of the cornerstones of effective cancer treatment is early diagnosis. In this context, the identification of proteins that can serve as cancer biomarkers in bodily fluids ("liquid biopsies") has gained attention over the last decade. Plasma and serum fractions of blood are the most commonly investigated sources of potential cancer liquid biopsy biomarkers.

Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours.

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population.

Cathelicidin-3 Associated With Serum Extracellular Vesicles Enables Early Diagnosis of a Transmissible Cancer.

The identification of practical early diagnostic biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumor disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumor lesions.

Expression of the Nonclassical MHC Class I, Saha-UD in the Transmissible Cancer Devil Facial Tumour Disease (DFTD).

Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells.

Challenges of an Emerging Disease: The Evolving Approach to Diagnosing Devil Facial Tumour Disease.

Devil Facial Tumour Disease (DFTD) is an emerging infectious disease that provides an excellent example of how diagnostic techniques improve as disease-specific knowledge is generated. DFTD manifests as tumour masses on the faces of Tasmanian devils, first noticed in 1996. As DFTD became more prevalent among devils, karyotyping of the lesions and their devil hosts demonstrated that DFTD was a transmissible cancer.

Extracellular vesicle proteomes of two transmissible cancers of Tasmanian devils reveal tenascin-C as a serum-based differential diagnostic biomarker.

The iconic Tasmanian devil (Sarcophilus harrisii) is endangered due to the transmissible cancer Devil Facial Tumour Disease (DFTD), of which there are two genetically independent subtypes (DFT1 and DFT2). While DFT1 and DFT2 can be differentially diagnosed using tumour biopsies, there is an urgent need to develop less-invasive biomarkers that can detect DFTD and distinguish between subtypes. Extracellular vesicles (EVs), the nano-sized membrane-enclosed vesicles present in most biofluids, represent a valuable resource for biomarker discovery.

NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers.

Purpose: Downregulation of MHC class I (MHC-I) is a common immune evasion strategy of many cancers. Similarly, two allogeneic clonal transmissible cancers have killed thousands of wild Tasmanian devils (Sarcophilus harrisii) and also modulate MHC-I expression to evade anti-cancer and allograft responses. IFNG treatment restores MHC-I expression on devil facial tumor (DFT) cells but is insufficient to control tumor growth.

Mesenchymal plasticity of devil facial tumour cells during in vivo vaccine and immunotherapy trials.

Immune evasion is critical to the growth and survival of cancer cells. This is especially pertinent to transmissible cancers, which evade immune detection across genetically diverse hosts. The Tasmanian devil (Sarcophilus harrisii) is threatened by the emergence of Devil Facial Tumour Disease (DFTD), comprising two transmissible cancers (DFT1 and DFT2).

Incidence of and Risk Factors for Failed Induction of Labor Using a Contemporary Definition.

Objective: To estimate the incidence of failed induction of labor and the associated patient risk factors.

Methods: We performed a case-control study from a cohort of nulliparous women who delivered between 39 and 41 weeks of gestation after an induction of labor in one of seven hospitals. Cases of failed induction were defined using the Obstetric Care Consensus criteria (ie, cesarean delivery performed in early labor [less than 6 cm dilatation] after at least 12 hours of oxytocin administration from membrane rupture).

Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils.

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018.

Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells.

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis.

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers.

Around 40% of humans and Tasmanian devils () develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species.

Assessing Medical Student Interest in Training About Medications for Opioid Use Disorder: A Pilot Intervention.

Objective: Educating medical students about buprenorphine may lessen barriers to providing treatment for opioid use disorder (OUD) by addressing stigma, removing the need to complete training while practicing, and normalizing it as a pharmacological option. We conducted a needs assessment to measure student interest in buprenorphine waiver training and pilot tested an online course with an in-person discussion for feasibility and acceptability.

Methods: All 2019 graduating students were surveyed to assess interest in completing buprenorphine waiver training and understand in which format they preferred to receive the training.

A Devil of a Transmissible Cancer.

Devil facial tumor disease (DFTD) encompasses two independent transmissible cancers that have killed the majority of Tasmanian devils. The cancer cells are derived from Schwann cells and are spread between devils during biting, a common behavior during the mating season. The Centers for Disease Control and Prevention (CDC) defines a parasite as "An organism that lives on or in a host organism and gets its food from, or at, the expense of its host.

Curse of the devil: molecular insights into the emergence of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii).

The Tasmanian devil (Sarcophilus harrisii) is the only mammalian species known to be affected by multiple transmissible cancers. Devil facial tumours 1 and 2 (DFT1 and DFT2) are independent neoplastic cell lineages that produce large, disfiguring cancers known as devil facial tumour disease (DFTD). The long-term persistence of wild Tasmanian devils is threatened due to the ability of DFTD cells to propagate as contagious allografts and the high mortality rate of DFTD.