Tracking the gene expression programs and clonal relationships that underlie mast, myeloid, and T lineage specification from stem cells.

T cells develop from hematopoietic progenitors in the thymus and protect against pathogens and cancer. However, the emergence of human T cell-competent blood progenitors and their subsequent specification to the T lineage have been challenging to capture in real time. Here, we leveraged a pluripotent stem cell differentiation system to understand the transcriptional dynamics and cell fate restriction events that underlie this critical developmental process.

C1QTNF Related protein 8 (CTRP8) is a marker of myeloid derived innate immune cell populations in the human breast cancer microenvironment.

Innate immune cells in the tumor microenvironment (TME) play an important role in breast cancer (BC) metastatic spread and influence patient survival. Macrophages differentiate along a proinflammatory M1 to protumorigenic M2 phenotype spectrum which affects distinct functions, like angiogenesis and cytokine production, and modulates BC aggressiveness and affects patient survival. Mast cells (MCs) are myeloid derived cells that serve as the first line of innate immune defense but their role in the TME of BC is not well understood.

Netrin-1 and UNC5B Cooperate with Integrins to Mediate YAP-Driven Cytostasis.

Unlabelled: Opposite expression and pro- or anti-cancer function of YAP and its paralog TAZ/WWTR1 stratify cancers into binary YAPon and YAPoff classes. These transcriptional coactivators are oncogenic in YAPon cancers. In contrast, YAP/TAZ are silenced epigenetically along with their integrin and extracellular matrix adhesion target genes in neural and neuroendocrine YAPoff cancers (e.

A Population-Based Matched Cohort Study of Digestive System Cancer Incidence and Mortality in Individuals With and Without Inflammatory Bowel Disease.

Introduction: To study digestive system cancer risks in individuals with inflammatory bowel diseases (IBDs) in the biologic era.

Methods: We used population-level administrative and cancer registry data from Ontario, Canada, (1994-2020) to compare people with IBD to matched controls (1:10 by sex and birth year) on trends in age-sex standardized cancer incidence and risk ratios of incident cancers and cancer-related deaths.

Results: Among 110,919 people with IBD and 1,109,190 controls, colorectal cancer incidence (per 100,000 person-years) declined similarly in people with ulcerative colitis (average annual percentage change [AAPC] -1.

Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.

Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2-5% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes on whole exome sequencing data of 23 FASD-diagnosed individuals.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.

Background: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality.

PROTACs: Current and Future Potential as a Precision Medicine Strategy to Combat Cancer.

Proteolysis targeting chimeras (PROTAC) are an emerging precision medicine strategy, which targets key proteins for proteolytic degradation to ultimately induce cancer cell killing. These hetero-bifunctional molecules hijack the ubiquitin proteasome system to selectively add polyubiquitin chains onto a specific protein target to induce proteolytic degradation. Importantly, PROTACs have the capacity to target virtually any intracellular and transmembrane protein for degradation, including oncoproteins previously considered undruggable, which strategically positions PROTACs at the crossroads of multiple cancer research areas.

Measuring the impact of COVID-19 on cancer survival using an interrupted time series analysis.

Background: Few studies have investigated the impact of the COVID-19 pandemic on cancer survival. Those studies that have included pandemic vs prepandemic comparisons can mask differences during different periods of the pandemic such as COVID-19 waves. The objective of this study was to investigate the impact of the COVID-19 pandemic on cancer survival using an interrupted time series analysis and to identify time points during the pandemic when observed survival deviated from expected survival.

Steroid-Induced Hyperglycemia and Its Effect on Outcomes of R-CHOP Chemotherapy for Diffuse Large B-Cell Lymphoma.

Unlabelled: Large doses of steroids are integral to R-CHOP, a first-line systemic therapy for diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin Lymphoma (NHL). Patients on R-CHOP often develop clinically significant hyperglycemia from steroids. There is evidence of harms from steroid-induced hyperglycemia in the context of chemotherapy which are associated with a reduction in overall survival.

Long-term Survival Among Patients With De Novo Human Epidermal Growth Receptor 2-Positive Metastatic Breast Cancer in Manitoba.

Objectives: Although metastatic breast cancer (MBC) is considered incurable, human epidermal growth receptor 2 (HER2)-directed therapy has improved outcomes significantly, with some patients experiencing durable responses to treatment. The aim of this study was to identify potential predictors of long-term survival (LTS) among patients with de novo HER2-positive MBC who received HER2-directed treatment.

Methods: Eligible patients from 2008 to 2018 were identified using the Manitoba Cancer Registry.

Cancer incidence during the COVID-19 pandemic by region of residence in Manitoba, Canada: A cancer registry-based interrupted time series study.

Introduction: Health care in Manitoba, Canada is divided into five regions, each with unique geographies, demographics, health care access, and health status. COVID-19-related restrictions and subsequent responses also differed by region. To understand the impact of the pandemic on cancer incidence in the context of these differences, we examined age-standardized cancer incidence rates by region over time before and after the COVID-19 pandemic.

Province-Wide Ascertainment of Lynch Syndrome in Manitoba.

Background & Aims: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years.

Methods: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT).

New Cancer Diagnoses Before and During the COVID-19 Pandemic.

Importance: Disruptions to health care during the COVID-19 pandemic may have led to missed cancer diagnoses. It is critical to evaluate the association between the COVID-19 pandemic and cancer incidence to address public and patient anxiety, inform recovery efforts, and identify strategies to reduce the system's vulnerability to future disruptions.

Objective: To examine the association between the COVID-19 pandemic and cancer incidence in Manitoba, Canada.

Evaluation of the Impact of the Urgent Cancer Care Clinic on Emergency Department Visits, Primary Care Clinician Visits, and Hospitalizations in Winnipeg, Manitoba.

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015.

Clinical Outcomes in a Large Canadian Centralized CLL Clinic Based on Treatment and Molecular Factors over a Decade.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score.