This work represents the first set of HU scores for numerous cancer sites derived using Canadian preference weights. The dataset demonstrated construct validity and HU scores varied by general socio-demographic and clinical parameters.
As part of a project to identify nove1 maize (Zea mays 1. cv B73) genes functionally, we have partially sequenced 130 randomly selected clones from a maize leaf cDNA library. Data base comparisons revealed seven previously sequenced maize cDNAs and 18 cDNAs with sequence similarity to related maize genes or to genes from other organisms. One hundred five cDNAs show little or no similarity to previously sequenced genes. Our results also establish the suitability of this library for large-scale sequencing in terms of its large insert size, proper insert orientation, and low duplication rate.
Purpose Smoking cessation and increased physical activity (pa) have been linked to better outcomes in cancer survivors. We assessed whether socioeconomic factors influence changes in those behaviours after a cancer diagnosis. MethodsAs part of a cross-sectional study, a diverse group of cancer survivors at the Princess Margaret Cancer Centre (Toronto, ON), completed a questionnaire about past and current lifestyle behaviours and perceptions about the importance of those behaviours with respect to their health. The influence of socioeconomic indicators on smoking status and physical inactivity at 1 year before and after diagnosis were assessed using multivariable logistic regression with adjustment for clinico-demographic factors. ResultsOf 1222 participants, 1192 completed the smoking component. Of those respondents, 15% smoked before diagnosis, and 43% of those smokers continued to smoke after. The proportion of survivors who continued to smoke increased with lower education level (p = 0.03). Of the 1106 participants answering pa questions, 39% reported being physically inactive before diagnosis, of whom 82% remained inactive afterward. Survivors with a lower education level were most likely to remain inactive after diagnosis (p = 0.003). Lower education level, household income, and occupation were associated with the perception that pa had no effect or could worsen fatigue and quality of life (p ≤ 0.0001).Conclusions In cancer survivors, education level was a major modifier of smoking and pa behaviours. Lower socioeconomic status was associated with incorrect perceptions about pa. Targeting at-risk survivors by education level should be evaluated as a strategy in cancer survivorship programs.
There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (Po0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P ¼ 0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances.
BackgroundThe Hedgehog (Hh) signaling pathway is active in esophageal adenocarcinoma (EAC). We used a patient-derived murine xenograft (PDX) model of EAC to evaluate tumour response to conventional treatment with radiation/chemoradiation with or without Hh inhibition. Our goal was to determine the potential radioresistance effects of Hh signaling and radiosensitization by Hh inhibitors.MethodsPDX models were treated with radiation, chemotherapy or combined chemoradiation. Tumour response was measured by growth delay. Hh transcript levels (qRT-PCR) were compared among frozen tumours from treated and control mice. 5E1, a monoclonal SHH antibody, or LDE225, a clinical SMO inhibitor (Novartis®) inhibited Hh signaling.ResultsPrecision irradiation significantly delayed xenograft tumour growth in all 7 PDX models. Combined chemoradiation further delayed growth relative to either modality alone in three of six PDX models. Following irradiation, two of three PDX models demonstrated sustained up-regulation of Hh transcripts. Combined LDE225 and radiation, and 5E1 alone delayed growth relative to either treatment alone in a Hh-responsive PDX model, but not in a non-responsive model.ConclusionHh signaling mediates the radiation response in some EAC PDX models, and inhibition of this pathway may augment the efficacy of radiation in tumours that are Hh dependent.
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