PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN ؉/؊ mice have elevated levels of phosphorylated Akt and activated p70͞S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR͞ RAFT͞FRAP reduced neoplastic proliferation, tumor size, and p70͞S6 kinase activity, but did not affect the status of Akt. These data suggest that p70͞S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.
Regular screening mammography reduces breast cancer mortality. However, in women with dense breasts, the performance of screening mammography is reduced, which is reflected in higher interval cancer rates (ICR). In Canada, population-based screening mammography programs generally screen women biennially; however, some provinces and territories offer annual mammography for women with dense breast tissue routinely and/or on recommendation of the radiologist. This study compared the ICRs in those breast screening programs with a policy of annual vs. those with biennial screening for women with dense breasts. Among 148,575 women with dense breasts screened between 2008 to 2010, there were 288 invasive interval breast cancers; screening programs with policies offering annual screening for women with dense breasts had fewer interval cancers 63/70,814 (ICR 0.89/1000, 95% CI: 0.67-1.11) compared with those with policies of usual biennial screening 225/77,761 (ICR 1.45 /1000 (annualized), 95% CI: 1.19-1.72) i.e. 63% higher (p = 0.0016). In screening programs where radiologists’ screening recommendations were able to be analyzed, a total of 76,103 women were screened, with 87 interval cancers; the ICR was lower for recommended annual (65/69,650, ICR 0.93/1000, 95% CI: 0.71, 1.16) versus recommended biennial screening (22/6,453, ICR 1.70/1000 (annualized), 95%CI: 0.70, 2.71)(p = 0.0605). Screening program policies of annual as compared with biennial screening in women with dense breasts had the greatest impact on reducing interval cancer rates. We review our results in the context of current dense breast notification in Canada.
Revue canadienne des soins respiratoires et critiques et de la médecine du sommeil
Healthy public policy plays an essential role in a comprehensive public health approach to preventing cancer and chronic disease. Public policies spread through the ‘policy diffusion’ process, enabling governments to learn from another’s enacted policy solutions. The Prevention Policies Directory (the Directory), an online database of municipal, provincial/territorial, and federal cancer and chronic disease prevention policies from across Canada, was developed to facilitate the diffusion of healthy public policies and support the work of prevention researchers, practitioners, and policy specialists. This information technology solution was implemented, through a participatory engagement approach, as a communication channel or policy knowledge transfer tool. It also addressed the intrinsic shortcomings of environmental scanning for policy surveillance and monitoring. A combination of quantitative web metrics and qualitative anecdotal evidence have illustrated that the Directory is becoming an important tool for healthy public policy surveillance and policy diffusion in Canada.
OBJECTIVES:The Canadian Partnership Against Cancer funded 12 large-scale knowledge to action cancer and chronic disease prevention projects between 2009 and 2016 through the Coalitions Linking Action and Science for Prevention (CLASP) initiative. Two projects, Healthy Canada by Design (HCBD) and Children's Mobility, Health and Happiness (CMHH), developed policies to address physical activity and the built environment through a multisectoral approach. A qualitative analysis involving a review of 183 knowledge products and 8 key informant interviews was conducted to understand what policy changes occurred, and the underlying critical success factors, through these projects. SETTING:Both projects worked at the local level to change physical activity and built environment policy in 203 sites, including municipalities and schools. Both projects brought multisectoral expertise (e.g., public health, land use planning, transportation engineering, education, etc.) together to inform the development of local healthy public policy in the areas of land use, transportation and school travel planning. INTERVENTION:Through the qualitative analysis of the knowledge products and key informant interviews, 163 policies were attributed to HCBD and CMHH work. OUTCOMES:Fourteen "pathways to policy" were identified as critical success factors facilitating and accelerating the development and implementation of physical activity and built environment policy. Of the 14 pathways to policy, 8 had a focus on multisectoral collaboration. IMPLICATIONS:The lessons learned from the CLASP experience could support enhanced multisectoral collaborations to accelerate the development and implementation of physical activity and built environment policy in new jurisdictions across Canada and internationally.KEY WORDS: Public health; policy; physical activity; environment design; city planning; collaboration La traduction du résumé se trouve à la fin de l'article.
Background The human papillomavirus (hpv) is a common sexually transmitted infection and a primary cause of cervical cancer. The Government of Canada has set a target of reaching 90% hpv vaccine coverage among adolescents by 2025. Here, we examine hpv vaccine uptake in school-based immunization programs across Canada and explore how achieving the 90% target could affect the future incidence of cervical cancer, mortality, and health system expenditures in a cohort of Canadian women.Methods Data for hpv vaccine uptake in the most recent reported school year available in each jurisdiction were provided in 2017 by jurisdictional school-based immunization programs and were used to estimate a national weighted average of 67%. The OncoSim microsimulation model (version 2.5) was used to compare 3 different levels of hpv vaccine uptake (0%, 67%, 90%) on health and economic outcomes for a hypothetical cohort of all 5- to 10-yearold girls in Canada in 2015.Results Vaccine uptake for girls in school-based programs varied from 55.0% to 92.0% in the jurisdictions reviewed. The OncoSim model projects that increasing uptake to 90% from 67% would result in a 23% reduction in cervical cancer incidence rates (to 3.1 cases from 4.0 cases per 100,000, averaged across the lifetime of the cohort) and a 23% decline in the average annual mortality rate (to 1.0 deaths from 1.3 deaths per 100,000). Finally, the model projects that the health system will incur a cost of $9 million (1% increase) during the lifetime of the cohort if uptake is increased to 90% from 67%. Costs are discounted (1.5%) and expressed in 2016 Canadian dollars. Costs reflect the payer perspective.Conclusions Our model shows that increasing hpv vaccine uptake to 90% from current levels for girls in schoolbased immunization programs could result in substantial reductions in the future incidence and mortality rates for cervical cancer in Canada.
Given the lack of progress in breast cancer prevention, the California Breast Cancer Research Program (CBCRP) plans to apply current scientific knowledge about breast cancer to primary prevention at the population level. This paper describes the first phase of Californians Linking Action with Science for Prevention of Breast Cancer (CLASP-BC). The foci of Phase 1 are building coalitions and coalition capacity building through community engagement in community-based participatory research (CBPR) and dissemination and implementation (D&I) research training. Based on the successful implementation and evaluation of Phase 1, the foci of Phase 2 (presented separately in this special issue) will be to translate the California Breast Cancer Prevention Plan overarching goal and specific intervention goals for 23 breast cancer risk and protective factors strategies into evidence-informed interventions (EIIs) that are disseminated and implemented across California. CLASP-BC is designed to identify, disseminate and implement high-impact, population-based prevention approaches by funding large scale EIIs, through multi-jurisdictional actions, with the intent to decrease the risk of breast cancer and other chronic diseases (sharing common risk factors), particularly among racial/ethnic minorities and medically underserved populations in California.
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