Socio-economic differences in cancer survival are now well documented. The explanatory power of stage at diagnosis, although great, should not detract from the evidence of differential treatment between social groups. Neither factor can completely explain the observed socio-economic differences in survival, however, and the importance of differences in tumour and patient factors should now be quantified.
The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for developmental progression throughout intrauterine development. One of the most common complications during pregnancy is insufficient growth of the fetus, a problem termed intrauterine growth restriction (IUGR) that is most frequently rooted in a malfunctional placenta. Together with conventional gene targeting approaches, recent advances in screening mouse mutants for placental defects, combined with the ability to rapidly induce mutations in vitro and in vivo by CRISPR-Cas9 technology, has provided new insights into the contribution of the genome to normal placental development. Most importantly, these data have demonstrated that far more genes are required for normal placentation than previously appreciated. Here, we provide a summary of common types of placental defects in established mouse mutants, which will help us gain a better understanding of the genes impacting on human placentation. Based on a recent mouse mutant screen, we then provide examples on how these data can be mined to identify novel molecular hubs that may be critical for placental development. Given the close association between placental defects and abnormal cardiovascular and brain development, these functional nodes may also shed light onto the etiology of birth defects that co-occur with placental malformations. Taken together, recent insights into the regulation of mouse placental development have opened up new avenues for research that will promote the study of human pregnancy conditions, notably those based on defects in placentation that underlie the most common pregnancy pathologies such as IUGR and pre-eclampsia.
In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.
We examined national trends and socioeconomic inequalities in cancer survival in England and Wales during the 1990s, using population-based data on 2.2 million patients who were diagnosed with one of the 20 most common cancers between 1986 and 1999 and followed up to 2001. Patients were assigned to one of five deprivation categories (from 'affluent' to 'deprived') using characteristics of their electoral ward of residence at diagnosis. We estimated relative survival up to 5 years after diagnosis, adjusting separately in each deprivation category for background mortality by age, sex and calendar period. We estimated trends in survival and in the difference in survival between deprivation categories ('deprivation gap') over the periods 1986 -90, 1991 -95 and 1996 -99. We used period analysis to examine likely survival rates in the near future. Survival improved for most cancers in both sexes during the 1990s, and appears likely to continue improving for most cancers in the near future. The deprivation gap in survival between rich and poor was wider for patients diagnosed in the late 1990s than in the late 1980s. Increases in cancer survival in England and Wales during the 1990s are shown to be significantly associated with a widening deprivation gap in survival.
Background:Socioeconomic inequalities in survival were observed for many cancers in England during 1981–1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan.Materials and method:We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996–2006, followed up to 31 December 2007. Three periods were defined: 1996–2000 (before the Cancer Plan), 2001–2003 (initialisation) and 2004–2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods.Results:Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1-year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis.Conclusion:The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups.
The findings indicate slightly faster improvement in 1-year survival in England than in Wales during 2004-06, whereas the opposite was true during 2001-03. This reversal of survival trends in 2001-03 and 2004-06 between England and Wales is much less obvious for 3-year survival. These different patterns of survival suggest some beneficial effect of the NHS cancer plan for England, although the data do not so far provide a definitive assessment of the effectiveness of the plan.
Mammalian reproductive performance declines rapidly with advanced maternal age. This effect is largely attributed to the exponential increase in chromosome segregation errors in the oocyte with age. Yet many pregnancy complications and birth defects that become more frequent in older mothers, in both humans and mice, occur in the absence of karyotypic abnormalities. Here, we report that abnormal embryonic development in aged female mice is associated with severe placentation defects, which result from major deficits in the decidualisation response of the uterine stroma. This problem is rooted in a blunted hormonal responsiveness of the ageing uterus. Importantly, a young uterine environment can restore normal placental as well as embryonic development. Our data highlight the pivotal, albeit under-appreciated, impact of maternal age on uterine adaptability to pregnancy as major contributor to the decline in reproductive success in older females.
Cancer incidence, survival and mortality are essential population-based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population-based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use.Measuring the burden of cancer in a population is essential for public health and cancer control. Reliable estimates of the cancer burden can provide a comprehensive picture of how the impact of cancer varies between geographic areas and between population strata. These estimates, in turn, inform the development of cancer control strategies. Increasingly, survival trends are also being used to assess the efficacy of cancer strategies in reducing the impact of cancer over time.Incidence, survival and mortality are commonplace terms in epidemiology. For many years, they have been the principal measures used in population-based research to explore the causes (incidence) and outcomes of cancer (survival and mortality), and to assess its management. In England, for example, population-based estimates of cancer mortality have been published in some form since the 1850s, 1 and national population-based estimates of incidence and survival have been published since the 1950s.2 Nevertheless, confusion and misunderstanding still surround the estimation and interpretation of these indicators.One recent examination of the WHO mortality database showed that among 30 European countries, the UK had one of the largest reductions in breast cancer mortality over the period 1989-2006. 3 As breast cancer survival in the late 1990s was lower in the UK than elsewhere in Europe, 4 the authors postulated that differences in screening intensity between countries had resulted in spurious survival estimates, and concluded that "mortality data are a more realistic measure of successful cancer control than cancer survival, as the latter is influenced by changes in cancer incidence." 3 This despite the fact that mortality is itself affected by incidence and survival.Again, in 2011, controversy followed publication of an international comparison of survival from four common cancers during the period 1995-2007 in Australia, Canada, Denmark, Norway, Sweden and the UK, based on population-based cancer registry data. 5 The study found persistently lower survival in Denmark and the UK for all four cancers, particularly in the first year after diagnosis. The authors noted th...
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