Browsing by Author "Bebb, Gwyn"

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    ATM loss in non-small cell lung cancer: Therapeutic implications for platinum-based therapies
    (2017) Moore, Jarrett; Bebb, Gwyn; Lees-Miller, Susan; Jirik, Frank; Cobb, Jennifer
    Therapeutic strategies for non-small cell lung cancer (NSCLC), such as platinum-based antineoplastic therapies (platins), generate DNA breaks and stimulate DNA damage response pathways. A key component of the response to DNA damage is the protein ataxia telangiectasia mutated (ATM). Evidence from the Glans-Look Database suggests that patients with low tumour ATM protein expression have improved disease-free survival rates after adjuvant platin therapy. I hypothesize that ATM-deficient tumours will be innately sensitive to platin therapies. NSCLC cell lines were treated with increasing concentrations of platins and assessed for ATM activation. ATM knockdown cell lines were generated using shRNA and investigated for cisplatin sensitivity. ATM-proficient cell lines demonstrated increased levels of phosphorylated-ATM in response to platins. ATM knockdowns had increased sensitivity to IR and a trend toward increased sensitivity to cisplatin. It is evident that platin exposure induced an ATM mediated signaling, however the predictive capabilities for ATM-loss to platin sensitivity is still unclear.
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    Feasibility of a multimodal exercise, nutrition, and palliative care intervention in advanced lung cancer
    (2021-02-13) Ester, Manuel; Culos-Reed, S. N; Abdul-Razzak, Amane; Daun, Julia T; Duchek, Delaney; Francis, George; Bebb, Gwyn; Black, Jennifer; Arlain, Audra; Gillis, Chelsia; Galloway, Lyle; Capozzi, Lauren C
    Abstract Background Advanced lung cancer patients face significant physical and psychological burden leading to reduced physical function and quality of life. Separately, physical activity, nutrition, and palliative symptom management interventions have been shown to improve functioning in this population, however no study has combined all three in a multimodal intervention. Therefore, we assessed the feasibility of a multimodal physical activity, nutrition, and palliative symptom management intervention in advanced lung cancer. Methods Participants received an individually tailored 12-week intervention featuring in-person group-based exercise classes, at-home physical activity prescription, behaviour change education, and nutrition and palliative care consultations. Patients reported symptom burden, energy, and fatigue before and after each class. At baseline and post-intervention, symptom burden, quality of life, fatigue, physical activity, dietary intake, and physical function were assessed. Post-intervention interviews examined participant perspectives. Results The multimodal program was feasible, with 44% (10/23) recruitment, 75% (75/100) class attendance, 89% (8/9) nutrition and palliative consult attendance, and 85% (17/20) assessment completion. Of ten participants, 70% (7/10) completed the post-intervention follow-up. Participants perceived the intervention as feasible and valuable. Physical activity, symptom burden, and quality of life were maintained, while tiredness decreased significantly. Exercise classes prompted acute clinically meaningful reductions in fatigue, tiredness, depression, pain, and increases in energy and well-being. Conclusion A multimodal physical activity, nutrition, and palliative symptom management intervention is feasible and shows potential benefits on quality of life that warrant further investigation in a larger cohort trial. Trial registration NCT04575831 , Registered 05 October 2020 – Retrospectively registered.
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    Gender Disparities in NSCLC: A Systematic Review
    (2018-01-26) Alsaadoun, Noor Asaad; Bebb, Gwyn; Hollenberg, Morley; Hao, Diseree; Riabowol, Karl; Kopciuk, Karen
    Lung cancer is the second most common malignancy in both men and women. Non-small cell lung cancer (NSCLC) represents 80-85% of cases while the remaining 15 – 20% are small cell lung cancer. Lung cancer incidence in men has steadily decreased since the mid-1980s while it has increased in women. The sex differences in smoking behavior in the last two decades partly account for this incidence pattern. Interestingly, epidemiological evidence suggests that sex alone impacts most facets of lung cancer including the incidence, susceptibility, severity, and molecular basis of the disease; however, there is lack of consensus on the etiology of the gender-based differences as well its magnitude. Therefore, we conducted an evidence-based research of the literature to identify and describe sex-associated characteristics among non-small cell lung cancer patients. We identified all potentially relevant articles published in English by searching Medline between 1996 and 2016, worldwide. Using a systematic review protocol, all abstracts were reviewed for eligibility, and relevant studies meeting inclusion criteria were retained. We included all studies on NSCLC and its main subtypes for both men and women of age over 45. Pooled data was analyzed using a semi-parametric longitudinal regression model and an ANOVA two-way test. A data-visualization tool was used to demonstrate NSCLC incidence distribution and its sex-based disparities around the world. Our data found sex-based disparities in NSCLC incidence rates, and a possible increase in female’s risk of acquiring this disease. In addition, data reveal that both race and sex have a significant effect on NSCLC incidence rates and these trends changed with time. Our findings also illustrate that global trends are not always reflective of regional ones. Results also confirms that adenocarcinoma in women is the most commonly diagnosed histology regardless of their race; however, data indicate that Asians are the dominant race to express adenocarcinomas in their lungs. The objective of this systematic literature review is to more precisely describe this gender disparity among NSCLC patients worldwide and summarize current opinions about the molecular basis for these observations. Our findings serve as a basis to begin to resolve the inherent controversies in the research, and highlight the importance of the inclusion of sex as a risk modifier in the development of screening initiatives and therapies in NSCLC.
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    Treatment at Disease-progression in EGFR-mutated NSCLC Patients: Results from a single Canadian Institution
    (2016) Tudor, Roxana; Bebb, Gwyn; Kopciuk, Karen; Brenner, Darren; Tremblay, Alain; MacEachern, Paul
    Optimal treatment beyond disease-progression (PD) in non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations, treated with tyrosine kinase inhibitors (TKIs), is not well-defined. In this retrospective study, the following aims were set out: 1) compare outcomes and profile of EGFRmut+ NSCLC patients to large cohorts of lung-cancer patients from the Glans-Look lung cancer database -GLD; 2) examine the frequency of continuing TKI treatment beyond PD in EGFRmut+ patients; 3) examine overall survival (OS) and post-progression survival (PPS) according to clinicopathological characteristics and; 4) propose a new PD-scoring model to help guide subsequent treatment formulation. Compared to the GLD-NSCLC cohort without systemic chemotherapy, EGFRmut+ patients were more likely to be younger, female and Asian. Further, continuing TKI treatment beyond PD was associated with improved OS and PPS vs. discontinuation of TKI. A non-independent relationship between EGFRmutation type and smoking history was identified.