A5026680987- Muscle Physiology and Disorders
- Nutrition and Health in Aging
- Genetic Neurodegenerative Diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Adipose Tissue and Metabolism
- Autophagy in Disease and Therapy
- Cancer survivorship and care
- Frailty in Older Adults
- Cancer-related cognitive impairment studies
- Medical Image Segmentation Techniques
- Childhood Cancer Survivors' Quality of Life
- Body Composition Measurement Techniques
- Lung Cancer Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Muscle metabolism and nutrition
- Lung Cancer Treatments and Mutations
- AI in cancer detection
- Cardiovascular and exercise physiology
- Cerebral Palsy and Movement Disorders
- Diet and metabolism studies
- Cancer Treatment and Pharmacology
- Medical Imaging Techniques and Applications
- RNA modifications and cancer
- Pharmacogenetics and Drug Metabolism
Jewish General Hospital
2014-2025
McGill University
2011-2025
McGill University Health Centre
2021-2025
University Hospital of Larissa
2014
Institut Gustave Roussy
2014
Aintree University Hospital
2003-2013
University of Liverpool
2003-2013
Newcastle University
2002
Harvard University
2001-2002
Carrier (United States)
2001
Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal atrophying muscles found unique gene fragment induced more than ninefold fasted mice. We cloned gene, which expressed specifically striated muscles. Because mRNA also markedly increases because diabetes,...
Skeletal muscle atrophy is a debilitating response to starvation and many systemic diseases including diabetes, cancer, renal failure. We had proposed that common set of transcriptional adaptations underlie the loss mass in these different states. To test this hypothesis, we used cDNA microarrays compare changes content specific mRNAs muscles atrophying from causes. compared fasted mice, rats with cancer cachexia, streptozotocin-induced diabetes mellitus, uremia induced by subtotal...
Purpose Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous do not consider current trends toward obesity. Methods Canadian European (n = 8,160) formed a population-based data set. Body mass index (BMI) percent WL (%WL) were recorded, observed prospectively until death. Data entered into multivariable analysis controlling for age, sex, site, stage, performance status. Relationships BMI %WL to overall survival examined develop...
We previously identified a common set of genes, termed atrogenes, whose expression is coordinately induced or suppressed in muscle during systemic wasting states (fasting, cancer cachexia, renal failure, diabetes). To determine whether this transcriptional program also functions atrophy resulting from loss contractile activity and atrogene correlates with the rate weight loss, we used cDNA microarrays RT-polymerase chain reaction to analyze changes mRNA rat gastrocnemius disuse by...
In the last half of century, advances in systemic therapy cancer, including chemotherapy, hormonal therapy, targeted and immunotherapy have been responsible for improvements cancer related mortality developed countries even as population continues to age. Although such advancements yet benefit all types, therapies led an improvement overall survival both adjuvant metastatic setting many cancers. With pressure make available soon possible, side-effects therapies, particular long-term are not...
During fasting and many systemic diseases, muscle undergoes rapid loss of protein functional capacity. To define the transcriptional changes triggering atrophy energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles control food-deprived mice. Expression >94% genes did not change, but interesting patterns emerged among that were differentially expressed: 1) encoding polyubiquitin, ubiquitin extension proteins, (but all) proteasome subunits increased, which...
Restenosis after angioplasty is due predominantly to accumulation of vascular smooth muscle cells (VSMCs). The resistance restenosis pharmacological treatment has prompted investigation genes involved in VSMC proliferation. We have examined the effect on proliferation blocking expression c-myc proto-oncogene with antisense oligodeoxynucleotides, both vitro and a rat carotid artery injury model restenosis. Antisense oligodeoxynucleotides reduced average cell levels mRNA protein by 50-55%...
An automatic method for the accurate registration of computed tomography (CT) data with two camera‐calibrated radiographs is presented. The based on skull as visualized both in plain and digitally reconstructed from CT. A reference coordinate system established radiographic projection parameters obtained using an angiographic stereotactic localizer. CT‐derived are aligned iteratively at multiple resolutions until a best match found by adjusting position orientation CT set relative to system....
Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to degradation.To investigate whether enhanced locomotor muscles stable COPD, quantify autophagy-related gene expression these muscles, and identify mechanisms induction.Muscle biopsies were obtained from two cohorts control subjects COPD numbers autophagosomes vastus...
Key points Mitochondria are frequently implicated in the ageing of skeletal muscle, although role denervation modulating mitochondrial function muscle is unknown. We show that increased sensitivity to apoptosis initiation occurs prior evidence persistent and thus a primary defect worthy therapeutic targeting. However, at more advanced age, changes markedly impacted by sporadic myofibre denervation, suggesting mitochondrion may be less viable target. Abstract Experimental modulates function,...
Abstract Background Cancer‐associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented inflammatory biomarker C‐reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate associations CRP cancer‐associated (primary endpoint) overall survival (OS, secondary endpoint). Methods The set included...
Abstract Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but now implicated in causing impaired muscle function long-term survivors. However, no comprehensive assessment of skeletal mitochondrial functions survivors has been performed and the presence persistent chemotherapy-induced dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have used frequently ALL treatment (doxorubicin dexamethasone) up to...
There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL), have increased rates longterm skeletal muscle dysfunction. This places them at higher risk physical restriction and functional impairment well potentially contributing to observed increases in cardiovascular disease insulin resistance later life. The mechanisms underlying these changes are unknown but chemotherapy drugs used treatment for ALL strongly implicated. Normal growth, development...
Eccentric ergometer training (EET) is increasingly being proposed as a therapeutic strategy to improve skeletal muscle strength in various cardiorespiratory diseases, due the principle that lengthening actions lead high force-generating capacity at low cardiopulmonary load. One clinical population may particularly benefit from this chronic obstructive pulmonary disease (COPD), ventilatory constraints and locomotor dysfunction often limit efficacy of conventional exercise rehabilitation...
Muscle wasting is a common and prominent feature of advanced cancer, including lung cancer. Evidence from animal experiments suggests that accelerated proteolysis via the ubiquitin--proteasome pathway primary cause cancer-related cachexia. However, there are few data on role this in determining muscle human The present study was designed to measure whether skeletal gene expression components ubiquitin-proteasome and/or lysosomal proteolytic increased patients with early A total 36 cancer...
Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD). Although the exact cause is not firmly established, physical inactivity stress among proposed underlying mechanisms. Here, we assess impact COPD pathophysiology on DNA (mtDNA) integrity, biogenesis, cellular healthy controls. We hypothesized that high environment would yield...
Key points Chronic obstructive pulmonary disease (COPD) is largely caused by smoking, and patient limb muscle exhibits a fast fibre shift atrophy. We show that this associated with type grouping, suggesting recurring cycles of denervation–reinnervation underlie the shift. Compared to patients normal fat‐free mass index (FFMI), low FFMI exhibited an exacerbated shift, marked accumulation very small persistently denervated fibres, blunted denervation‐responsive transcript profile, failed...
Objectives Patients with cancer cachexia have severely impaired quality of life (QoL). Multidisciplinary, multimodal treatment approaches potential for stabilising weight and correcting other features this syndrome, but the impact on QoL is unknown. Methods A retrospective analysis in patients advanced cancer, referred management by a specialised multidisciplinary clinic (The McGill Cancer Nutrition Rehabilitation Program at Jewish General Hospital (CNR-JGH)). was assessed visits 1–3 using...