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Challenges in Environmental Governance: A Case Study of Risk Perceptions of Environmental Agencies Involved in Flood Management in the Hawkesbury-Nepean Region, Australia
Get PDFThe Efficacy of Targeting Cell Cycle Regulators in the Treatment of Medulloblastoma
No full textMedulloblastoma (MB) is the most common malignant brain tumour diagnosed in children. This type of brain tumour is comprised of four molecular subgroups: WNT, Sonic Hedgehog (SHH), Group 3, and Group 4. Previous research has indicated that these four subgroups have a diverse set of clinical features, genetics, and cell subpopulations driving the tumour progression and resistance to treatment. Currently, a combination of surgery, radiotherapy, and chemotherapy are used to treat MB. Standard of care chemotherapy is a very aggressive protocol characterized by high general cytotoxicity. The search for new drugs efficiently targeting MB at the source of its origin, both on the genetic as well as cellular level is of high importance. In our lab, we study a cell cycle regulatory protein called Speedy (Spy1) which is able to override select cell cycle checkpoints thereby providing an avenue for cells to over-proliferate and become cancerous. Speedy is implicated in the maintenance of the aggressive and expansive stem-like populations of tumour initiating cells in the most aggressive brain tumour known, glioblastoma multiforme. It is our hypothesis that Spy1 drives specific populations of tumour initiating cells in MB and the reduction of Spy1 levels will increase sensitivity to synthetic CKIs (cyclin-dependent kinase inhibitors). To address our hypothesis we have sorted select populations of patient-derived MB initiating cells and have manipulated levels of Spy1 and/or Cyclin E1 using a lentiviral system. We use a high throughput platform where manipulated human cancer cells are injected into Zebrafish prior to establishment of the acquired immune system. This allows us to determine the effect of specific factors on tumour foci formation and cell characteristics in the presence of an intact immune system. We also study the effect of specific drugs on these in vivo tumours. This work addressed the role of Spy1 and other cyclins on MB aggressiveness and response CKI treatment. The results from our study will not only aid in better understanding of MB biology and dissecting its molecular drivers, but will potentially contribute to improved design of therapy regimens and successful clinical outcome
Transcending Borders: Visions from the Windsor-Detroit Corridor
No full textTranscending Borders: Visions from the Windsor-Detroit Corrido
Medical Student Mental Health and Wellness Pilot Study
No full text['UNSDG 3: Good Health and Well-being (https://sdgs.un.org/goals/goal3)', 'UNSDG 4: Quality Education (https://sdgs.un.org/goals/goal4)']Viable, Healthy and Safe CommunitiesThis study hopes to examine by way of electronic survey sources of stress, impact on perceived performance, impact on intentions to quit, perceived support and needs amongst the future physicians (medical students) currently at a medical school in Southwestern Ontario. The goal is to address learners from multiple campuses to analyze global wellness. Each cohort can be studied independently or comparatively to identify potential differences within the various populations, i.e. first year vs third year medical students. The importance of addressing physician mental health and wellness as early as in medical school has been shown through previous research. A study by Dyrbye et. al. found higher rates of psychological distress (stress, depression, and anxiety) amongst medical students in the U.S. and Canada compared to the general population and age-matched individuals (Dyrbye et. al., 2006). This type of burnout can negatively impact emotional wellness, professionalism in the workplace, and adversely affect patient care (Shanafelt et. al., 2002). The results of this study can potentially identify and inform future strategies to prevent burnout and tailor coping strategies for undergraduate medical students
CURating Clinical Trials: Helping Patients Find Hope Through Clinical Trial Opportunities
No full text['UNSDG 3: Good Health and Well-being (https://sdgs.un.org/goals/goal3)', 'UNSDG 10: Reduced Inequalities (https://sdgs.un.org/goals/goal10)']Viable, Healthy and Safe CommunitiesClinical trials (CTs) are essential to the advancement of clinical therapies. However, only 5% of cancer patients enroll in CTs due to limited accessibility. Given that greater participation in CTs is¯associated with better patient outcomes, patients from smaller centers are at a disadvantage. The Clinical Trials Navigator (CTN) program was established by Hamm (2022) to help patients in smaller communities navigate and enroll in CTs. Between March 2019 to September 2022, 241 patients were enrolled in the CTN program. CTNs receive referrals, review medical information, and search five CT registries. Eligibility criteria is scrutinized. A second review of the CT list is conducted by two physicians. This updated study found that 75.9% of patients were in stage IV of their disease, and 51% had at least two prior lines of therapy. 61.4% of patients deceased at last follow up, with a median of 5.9 months from CTN program referral to death. CTNs identified a median of three trials for each patient. 25.5% of patients referred to a CT enrolled onto the recommended trial. The expanded CTN program resulted in CT enrolment of 8.5% of total patient data-base. The CTN program is a successful tool to identify CTs for cancer patients and improve CT accrual, as one quarter of patients referred to a CT by the CTN program have successfully enrolled. Further investigation into reasoning for early high mortality rates should be assessed. New initiatives to improve uptake of the CTN program are ongoing
Kaiso at the Crossroads: Understanding the Transition from Inflammatory Bowel Disease to Colorectal Cancer
No full textIndividuals diagnosed with inflammatory bowel disease (IBD) experience chronic intestinal inflammation and are at increased risk of developing colitis-associated colorectal cancer (CAC). However, as the mechanisms involved in the IBD-to-CAC transition are not fully elucidated, it is necessary to identify key molecular pathways involved in IBD. Colon biopsies derived from IBD patients, along with primary and metastatic colorectal cancer tumours display elevated expression of the transcription factor Kaiso. Notably, Kaiso over-expressing mice (KaisoTg/+) exhibit altered morphology and chronic intestinal inflammation. RNA-sequencing revealed dysregulated expression of genes linked to immune response in 6 weeks old KaisoTg/+ mice, which were subsequently examined for other factors contributing to inflammation. Immunohistochemical staining of KaisoTg/+ mouse intestines showed unaltered expression of proliferative, apoptotic, and neutrophil protein markers compared to non-transgenic (NonTg) mice. In addition, Gram staining revealed that there was no notable bacterial infiltration into the lamina propria that could explain the inflammatory phenotype. Collectively, our findings implicate Kaiso’s transcriptional activity as the key driver of the inflammatory phenotype, positioning KaisoTg/+ mice as a pivotal model to unravel the IBD-to-CAC transition
Assumption College Review: Vol. 2: no. 4 (1909: Jan.)
No full text49 numbered pagesTo view online at the Internet Archive: https://archive.org/details/assumptioncollegereview19090
Tuberin as a Tumor Suppressor and Molecular Integrator of Growth Signaling and Cell Cycle Control
No full textThe controlled growth and proliferation of a cell depend on its ability to sense both internal and external conditions and mount appropriate physiological responses. When such regulations go awry, various proliferative diseases may arise, including but not limited to cancers. Central to this control is the cell cycle, a precisely coordinated process that integrates metabolic signals, environmental conditions, and stress responses to maintain cellular homeostasis and ensure proper cell division. The tumour suppressor Tuberin (TSC2) is a key regulator of the cell cycle, yet its role in directly controlling cell proliferation remains poorly understood. Our lab has demonstrated that mitogen and nutrient signaling cascades converge on Tuberin to regulate its interaction with the mitotic cyclin, Cyclin B1 (CCNB1), thereby modulating mitotic entry in a context-dependent manner. Using in vitro ectopic expression and CRISPR/Cas-based approaches, coupled with imaging and cell cycle analysis, we show that weakening Tuberin's interaction with Cyclin B1—either by altering its phosphorylation status or introducing loss-of-function TSC2 mutations-accelerates mitotic entry, increases proliferation, and leads to aberrant cellular phenotypes. By characterizing Tuberin as a non-canonical regulator of mitotic entry, this research provides new insights into how metabolic signaling influences cell cycle progression. Given the frequent dysregulation of TSC2 in cancer and other proliferative disorders, elucidating this mechanism could reveal novel therapeutic targets for controlling aberrant cell division in disease
