Beatrice Hunter Cancer Research Institute

Background: Due to advances in technology, non-curative cancer patients are living longer with the burden of the disease. Physical activity (PA) has value as a supportive service for individuals at any point on the cancer care continuum, including advanced cancer. Objectives: The objective of this study was to understand how oncology care providers (OCPs), family/friend caregivers, and health system decision makers can include conversations of PA into care for those living with non-curative cancer. Methods: We conducted 24 semi-structured interviews guided by the Capability, Opportunity, Motivation–Behaviour (COM-B) model and further refined them using the Theoretical Domains Framework (TDF). The data were then analyzed using a directed content analysis, with a codebook generated based on the TDF. Results: Findings highlighted the need for targeted education and effective communication to address knowledge gaps, motivation-enhancing strategies to overcome emotional barriers, and streamlined referral processes to address systemic barriers to PA across the cancer care journey. Conclusions: There is an ongoing need to support individuals in living well, which involves not only addressing their immediate cancer diagnoses but also promoting overall health. This can be performed through PA, supported by their OCPs. This study further emphasizes the inclusion of PA discussions in cancer care.

Breast cancer is a leading cause of cancer mortality in women with triple-negative breast cancer (TNBC) presenting greater treatment challenges due to its aggressive disease progression. Understanding TNBC's unique cell signaling and gene expression profiles will reveal novel therapeutic strategies.Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as key regulators of gene expression and potential therapeutic targets. This study focuses on a TNBC-enriched lncRNA, non-coding RNA in the aldehyde dehydrogenase 1A pathway (NRAD1, previously LINC00284), which promotes progression in multiple cancers. Our analysis reveals that NRAD1 is central to miRNA-mRNA networks in TNBC cells, mediating cancer-promoting gene expression changes. Fractionation studies showed that NRAD1 is primarily located in the nucleus and mitochondria, with some cytoplasmic presence allowing for transcript-specific competitive endogenous RNA (ceRNA) interactions with miRNAs. However, NRAD1 primarily effects miRNAs independently of ceRNA activity, instead upregulating DICER (a miRNA biogenesis protein), altering sub-cellular distribution, and reducing biogenesis of mitochondria-localized miRNA (i.e., miR-4485-3p). These findings demonstrate novel regulatory interactions between the cancer-promoting lncRNA NRAD1 and miRNAs that alter gene expression in TNBC, expanding our understanding of regulatory lncRNA-miRNA effects, TNBC biology, and highlighting future therapeutic strategies for targeting non-coding RNAs.

The war in Ukraine has resulted in a mass exodus of Ukrainians fleeing their country and seeking resettlement in many countries, including Canada. There is a lack of literature, particularly qualitative, that explores past experiences with oral health care in the country of origin for newcomers and the experience of access and utilization of oral health care once in Canada. The increase in Ukrainian newcomers to Canada requires an exploration of barriers and facilitators to oral health care access to inform policy. To explore the barriers and facilitators to oral health care experienced by Ukrainian newcomers during resettlement in Nova Scotia, Canada. This study used a narrative qualitative methodology. Adult Ukrainian newcomers who arrived in Canada after the Russian invasion in 2022 were recruited via social media and through recruitment flyers advertised at the Immigrant Services Association of Nova Scotia. They were interviewed between February 17 and July 1, 2023, in the Ukrainian language. The interviews were audio recorded, transcribed, and analyzed via inductive and deductive line-by-line coding per the thematic analysis method. Codes were grouped to form categories and themes. Participants identified facilitators to oral health care that included friends and family, social networks, and information provided through the workplace. Barriers to access included cost, referral process, location and wait times for specialists, language, and lack of understanding the oral health care and dental insurance systems in Canada. Ukrainian newcomers to Nova Scotia face several barriers to oral health care access. Interventions to address these barriers should be considered to ensure equitable access to oral health care services during the resettlement process.Knowledge Transfer Statement:The results of this study may be used to inform policy to facilitate timely access to oral health care for Ukrainian newcomers. The findings may also guide professionals when providing oral health care services to Ukrainian newcomers. Addressing the barriers and maximizing the facilitators to oral health care services for this population could help to improve access to oral health care services and oral health outcomes.

ABSTRACT CD38, a multifunctional enzyme involved in NAD+ catabolism, is hypothesized to act as a metabolic checkpoint for antitumor CD8 T cells. A recent study discovered that, apart from its direct metabolic mechanisms, CD38-mediated RyR2-AKT-TCF1 signaling regulates responsiveness to anti-PD1 cancer therapy at the molecular level. These findings advocate multiprong CD38 targeting to overcome resistance to immune checkpoint blockade therapy.

Temporal RNA-sequencing (RNA-seq) studies of bulk samples provide an opportunity for improved understanding of gene regulation during dynamic phenomena such as development, tumor progression or response to an incremental dose of a pharmacotherapeutic. Moreover, single-cell RNA-seq (scRNA-seq) data implicitly exhibit temporal characteristics because gene expression values recapitulate dynamic processes such as cellular transitions. Unfortunately, temporal RNA-seq data continue to be analyzed by methods that ignore this ordinal structure and yield results that are often difficult to interpret. Here, we present Error Modelled Gene Expression Analysis (EMOGEA), a framework for analyzing RNA-seq data that incorporates measurement uncertainty, while introducing a special formulation for those acquired to monitor dynamic phenomena. This method is specifically suited for RNA-seq studies in which low-count transcripts with small-fold changes lead to significant biological effects. Such transcripts include genes involved in signaling and non-coding RNAs that inherently exhibit low levels of expression. Using simulation studies, we show that this framework down-weights samples that exhibit extreme responses such as batch effects allowing them to be modeled with the rest of the samples and maintain the degrees of freedom originally envisioned for a study. Using temporal experimental data, we demonstrate the framework by extracting a cascade of gene expression waves from a well-designed RNA-seq study of zebrafish embryogenesis and an scRNA-seq study of mouse pre-implantation and provide unique biological insights into the regulation of genes in each wave. For non-ordinal measurements, we show that EMOGEA has a much higher rate of true positive calls and a vanishingly small rate of false negative discoveries compared to common approaches. Finally, we provide two packages in Python and R that are self-contained and easy to use, including test data.

Canada is in the midst of an overdose crisis. The use of prescription opioids in Canada has increased steadily over the past two decades, with stark increases in opioid-induced respiratory depression and related deaths. Opioids are the mainstay of treatment for cancer-related pain. Patients with cancer are not immune to the risks associated with opioid use but are underrepresented in available literature outlining risk mitigation strategies. Pharmacists are ideally placed to employ opioid risk mitigation practices to support safe and effective opioid use for patients with cancer-related pain. However, the current attitudes, confidence, and safety practices of pharmacists around how to best support these patients are not known. This study was a descriptive environmental scan of pharmacists who provide direct patient care in Canada. An electronic questionnaire was built using the web based Opinio software. It was distributed via email by several provincial and national pharmacy organizations and online platforms. The questionnaire consisted of Likert-scale and open-ended questions and was open to participants for a 6-week period from February 12th to March 23rd, 2020. Analysis was conducted using descriptive statistics and qualitative content analysis. Eighty-one responses from pharmacists in nine provinces were included in the analysis. Respondents endorsed limited and varied practices when caring for patients receiving opioids for cancer-related pain. Further, they demonstrated wide ranging confidence and attitudes regarding opioid risk mitigation practices and beliefs. Less than 50% of pharmacists were aware of resources available for their patients with non-medical opioid use, and/or patients at high risk of opioid-induced respiratory depression. Education, resources, and communication were the most commonly reported perceived facilitators and barriers to resource use. Pharmacists in Canada report employing opioid risk mitigation practices with low and varied frequency when caring for patients receiving opioids for cancer-related pain. They endorsed varied confidence and limited awareness of available provider and patient resources. These findings may help inform the development of new education models and evidence-based guidelines. New education models and evidence-based guidelines will support pharmacists in their pharmaceutical care of this vulnerable patient population, ultimately aiming to improve patient outcomes.

IntroductionBreast cancer is the most common cancer among females in Canada. This study examines trends in socioeconomic inequalities in the incidence of breast cancer in Canada over time from 1992 to 2010.MethodsA census division level dataset was constructed using the Canadian Cancer Registry, Canadian Census of the Population and National Household Survey. A summary measure of the Concentration index (C), which captures inequality across socioeconomic groups, was used to measure income and education inequalities in breast cancer incidence over the 19-year period.ResultsThe crude breast cancer incidence increased in Canada between 1992 and 2010. Age-standardized C values indicated no income or education inequalities in breast cancer incidence in the years from 1992 to 2004. However, the incidence was significantly concentrated among females in high income and highly educated neighbourhoods almost half the time in the 6 most recent years (2005–2010). The trend analysis indicated an increase in breast cancer incidence among females living in high income and highly educated neighbourhoods.ConclusionBreast cancer incidence in Canada was associated with increased socioeconomic status in some more recent years. Our study findings provide previously unavailable empirical evidence to inform discussions on socioeconomic inequalities in breast incidence.

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12 billion vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amid an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discussion of the effects of viral infections on placental amino acid transport and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infections and vaccine technologies on drug metabolism and disposition, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness. SIGNIFICANCE STATEMENT: Altered pharmacokinetics of small molecule and complex molecule drugs and fetal brain distribution of amino acids following SARS-CoV-2 infection or immunization are possible. The proposed mechanisms involve decreased liver cytochrome P450 metabolism of small molecules, enhanced innate immune system metabolism of complex molecules, and altered placental and fetal blood-brain barrier amino acid transport, respectively. Future research is needed to understand the effects of these interactions on adverse drug responses, drug and vaccine safety, and effectiveness and fetal neurodevelopment.