Ovarian cancer molecular pathology.

Peer reviewe

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination

Mapping and linking supply- and demand-side measures in climate-smart agriculture. A review

Climate change and food security are two of humanity’s greatest challenges and are highly interlinked. On the one hand, climate change puts pressure on food security. On the other hand, farming significantly contributes to anthropogenic greenhouse gas emissions. This calls for climate-smart agriculture—agriculture that helps to mitigate and adapt to climate change. Climate-smart agriculture measures are diverse and include emission reductions, sink enhancements, and fossil fuel offsets for mitigation. Adaptation measures include technological advancements, adaptive farming practices, and financial management. Here, we review the potentials and trade-offs of climate-smart agricultural measures by producers and consumers. Our two main findings are as follows: (1) The benefits of measures are often site-dependent and differ according to agricultural practices (e.g., fertilizer use), environmental conditions (e.g., carbon sequestration potential), or the production and consumption of specific products (e.g., rice and meat). (2) Climate-smart agricultural measures on the supply side are likely to be insufficient or ineffective if not accompanied by changes in consumer behavior, as climate-smart agriculture will affect the supply of agricultural commodities and require changes on the demand side in response. Such linkages between demand and supply require simultaneous policy and market incentives. It, therefore, requires interdisciplinary cooperation to meet the twin challenge of climate change and food security. The link to consumer behavior is often neglected in research but regarded as an essential component of climate-smart agriculture. We argue for not solely focusing research and implementation on one-sided measures but designing good, site-specific combinations of both demand- and supply-side measures to use the potential of agriculture more effectively to mitigate and adapt to climate change

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Microarray-Based Oncogenic Pathway Profiling in Advanced Serous Papillary Ovarian Carcinoma

Introduction: The identification of specific targets for treatment of ovarian cancer patients remains a challenge. The objective of this study is the analysis of oncogenic pathways in ovarian cancer and their relation with clinical outcome. Methodology: A meta-analysis of 6 gene expression datasets was done for oncogenic pathway activation scores: AKT, beta-Catenin, BRCA, E2F1, EGFR, ER, HER2, INF alpha, INF gamma, MYC, p53, p63, PI3K, PR, RAS, SRC, STAT3, TNF alpha, and TGF beta and VEGF-A. Advanced serous papillary tumours from uniformly treated patients were selected (N = 464) to find differences independent from stage-, histology- and treatment biases. Survival and correlations with documented prognostic signatures (wound healing response signature WHR/genomic grade index GGI/invasiveness gene signature IGS) were analysed. Results: The GGI, WHR, IGS score were unexpectedly increased in chemosensitive versus chemoresistant patients. PR and RAS activation score were associated with survival outcome (p = 0.002; p = 0.004). Increased activations of beta-Catenin (p = 0.0009), E2F1 (p = 0.005), PI3K (p = 0.003) and p63 (p = 0.05) were associated with more favourable clinical outcome and were consistently correlated with three prognostic gene signatures. Conclusions: Oncogenic pathway profiling of advanced serous ovarian tumours revealed that increased beta-Catenin, E2F1, p63, PI3K, PR and RAS -pathway activation scores were significantly associated with favourable clinical outcome. WHR, GGI and IGS scores were unexpectedly increased in chemosensitive tumours. Earlier studies have shown that WHR, GGI and IGS are strongly associated with proliferation and that high-proliferative ovarian tumours are more chemosensitive. These findings may indicate opposite confounding of prognostic versus predictive factors when studying biomarkers in epithelial ovarian cancer