Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Early restriction of peripheral and proximal cell lineages during formation of the lung.

Abstract: To establish the timing of lineage restriction among endodermal derivatives, we developed a method to label permanently subsets of lung precursor cells at defined times during development by using Cre recombinase to activate floxed alkaline phosphatase or green fluorescent protein genes under control of doxycycline-dependent surfactant protein C promoter. Extensive or complete labeling of peripheral lung, thyroid, and thymic epithelia, but not trachea, bronchi, or gastrointestinal tract occurred when mice were exposed to doxycycline from embryonic day (E) 4.5 to E6.5. Nonoverlapping cell lineages of conducting airways (trachea and bronchi), as distinct from those of peripheral airways (bronchioles, acini, and alveoli), were established well before formation of the definitive lung buds at E9–9.5. At E11.5, the labeled precursors of peripheral lung were restricted to relatively few cells along the bronchial tubes and clusters in bronchial tips and lateral buds. Thereafter, these cells underwent marked expansion to form the entire gas-exchange region in the lung. This study demonstrates early restriction of endodermal progenitor cells forming peripheral as compared with proximal airways, identifies distinct cell lineages in conducting airways, and distinguishes neuroepithelial and tracheal–bronchial gland cell lineages from those lining peripheral regions of the lung. This system for conditional gene addition or deletion is useful for the study of lung morphogenesis and gene function in vivo, and identifies progenitor cells that may serve as useful targets for cell or gene replacement for pulmonary disorders.

Antiangiogenic Therapy: A Universal Chemosensitization Strategy for Cancer?

Abstract: For more than 50 years, a major goal of research in cancer therapeutics has been to develop universally effective agents that render cancer cells more sensitive to cytotoxic chemotherapy without substantially increasing toxicity to normal cells. The results of recent clinical trials indicate that certain antiangiogenic drugs may produce this long-sought effect. Here, I describe three distinct mechanisms that may help to explain the chemosensitizing activity of these drugs: normalizing tumor vasculature, preventing rapid tumor cell repopulation, and augmenting the antivascular effects of chemotherapy. I then discuss how these potential mechanisms might be exploited to maximize therapeutic efficacy.

Development of a measure of physical function for patients with bone and soft tissue sarcoma.

Abstract: Patients undergoing limb salvage surgery for bone and soft tissue sarcoma of the extremities experience significant physical disability as a result of life-preserving treatment The existing health status measures do not adequately evaluate physical function from the patient's perspective This paper presents the developmental studies item selection, of a new measure, The Toronto Extremity Salvage Score (TESS) Patients with bone and soft tissue sarcoma (76 upper and 83 lower extremity) were randomly selected and mailed the TESS Patients rated the severity and importance of physical disabilities; the response options included a ‘not applicable’; category and open-ended questions that allowed patients to suggest additional items for inclusion in the questionnaire Therefore, patient perceptions were used to determine item content Difficulty and importance frequencies were calculated and items rated “totally unimportant’ or ‘not applicable’ by 30% of the sample were eliminated Extra items identified 30% of the time were added to the questionnaire Internal consistency was evaluated by Cronbach's alpha Test-retest reliability and validity were evaluated on subsequent patient samples The intraclass correlation coefficient (ICC) was calculated for test-retest reliability and correlations with The Musculoskeletal Tumour Society Rating Scale (MSTS) were calculated for construct validity Standardized effect sizes were calculated as a measure of responsiveness Fifty upper extremity and sixty-six lower extremity patients responded to the mailed questionnaire No items were eliminated based on importance or not applicable ratings Sporting activities were identified as additional items in both the upper and lower extremity questionnaire High internal consistency was demonstrated: 094 for the lower and 092 for the upper extremity questionnaires respectively Test-retest reliability was evaluated at multiple time-points and the intraclass correlation coefficient was greater than 087 in all instances Construct validity was shown by a moderate correlation with the MSTS The effect sizes were large demonstrating responsiveness The use of patients' perceptions in determining the content of the TESS has resulted in a reliable and valid measure that is able to detect change over time