Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous versus Peritoneal Spread

Metastasis is the major cause of death in patients with colorectal carcinoma (CRC). The most common sites of metastasis are the liver and the peritoneum. Peritoneal carcinomatosis is often considered the end stage of the disease after the tumor has spread to the liver. However, almost half of CRC patients with peritoneal carcinomatosis do not present with liver metastasis. This brings up the question of whether peritoneal spread can still be considered as the end stage of a metastasized CRC or whether it should just be interpreted as a site of metastasis alternative to the liver. This review tries to discuss this question and summarize the current status of literature on potential characteristics in tumor biology in the primary tumor, i.e., factors (transcription factors and direct and indirect E-cadherin repressors) and pathways (WNT, TGF-beta, and RAS) modulating EMT, regulation of EMT on a posttranscriptional and posttranslational level (miRNAs), and angiogenesis. In addition to tumor-specific characteristics, factors in the tumor microenvironment, immunological markers, ways of transport of tumor cells, and adhesion molecules appear to differ between hematogenous and peritoneal spread. Factors such as integrins and exosomal integrins, cancer stem cell phenotype, and miRNA expression appear to contribute in determining the metastatic route. We went through each step of the metastasis process comparing hematogenous to peritoneal spread. We identified differences with respect to organotropism, epithelial-mesenchymal transition, angiogenesis and inflammation, and tumor microenvironment which will be further elucidated in this review. A better understanding of the underlying mechanisms and contributing factors of metastasis development in CRC has huge relevance as it is the foundation to help find specific targets for treatment of CRC

The southernmost beech (Fagus sylvatica) forests of Europe (Mount Etna, Italy): ecology, structural stand-type diversity and management implications

The southernmost European beech forests are located in the upper forest vegetation belt on Mount Etna volcano. Their standstructural patterns were analysed to assess the effects of the site-ecological factors and previous management practices on the forest structure. Five main structural-silvicultural types were identified among the main beech forest types: coppice, highmountain coppice (HMCo), high forest, coppice in conversion to high-forest and non-formal stand. A detailed standstructural analysis was carried out through measured dendrometric parameters and derived structural characters linked to both the horizontal and the vertical profiles. Plant regeneration processes were also assessed, and several biodiversity indicators were calculated. The collected data indicate a high variability of beech stand structures in relation to the heterogeneity of the site-ecological characteristics as well as to the effects of both natural and anthropic disturbance factors. The occurrence of particular stand structures along the altitude gradient on Mount Etna is evident. It is especially visible in the multi-stemmed HMCos in relation to the changing, and increasingly limiting, ecological factors, although at higher altitudes historical anthropic actions (felling) also have had an influence. Inside the Mediterranean area, these stands highlight their ecological marginality, in terms of both latitude and altitude, especially regarding current climate change processes

Effect of platelet inhibition with perioperative aspirin on survival in patients undergoing curative resection for pancreatic cancer: a propensity score matched analysis

BACKGROUND The importance of platelets in the pathogenesis of metastasis formation is increasingly recognized. Although evidence from epidemiologic studies suggests positive effects of aspirin on metastasis formation, there is little clinical data on the perioperative use of this drug in pancreatic cancer patients. METHODS From all patients who received curative intent surgery for pancreatic cancer between 2014 and 2016 at our institution, we identified 18 patients that took aspirin at time of admission and continued to throughout the inpatient period. Using propensity score matching, we selected a control group of 64 patients without aspirin intake from our database and assessed the effect of aspirin medication on overall, disease-free, and hematogenous metastasis-free survival intervals as endpoints. RESULTS Aspirin intake proved to be independently associated with improved mean overall survival (OS) (46.5 vs. 24.6 months, *p = 0.006), median disease-free survival (DFS) (26 vs. 10.5 months, *p = 0.001) and mean hematogenous metastasis-free survival (HMFS) (41.9 vs. 16.3 months, *p = 0.005). Three-year survival rates were 61.1% in patients with aspirin intake vs. 26.3% in patients without aspirin intake. Multivariate cox regression showed significant independent association of aspirin with all three survival endpoints with hazard ratios of 0.36 (95% CI 0.15-0.86) for OS (*p = 0.021), 0.32 (95% CI 0.16-0.63) for DFS (**p = 0.001), and 0.36 (95% CI 0.16-0.77) for HMFS (*p = 0.009). CONCLUSIONS Patients in our retrospective, propensity-score matched study showed significantly better overall survival when taking aspirin while undergoing curative surgery for pancreatic cancer. This was mainly due to a prolonged metastasis-free interval following surgery

Dynamics of initial carbon allocation after drought release in mature Norway spruce—Increased belowground allocation of current photoassimilates covers only half of the carbon used for fine‐root growth

After drought events, tree recovery depends on sufficient carbon (C) allocation to the sink organs. The present study aimed to elucidate dynamics of tree-level C sink activity and allocation of recent photoassimilates (C$_{new}$) and stored C in c. 70-year-old Norway spruce (Picea abies) trees during a 4-week period after drought release. We conducted a continuous, whole-tree $^{13}$C labeling in parallel with controlled watering after 5 years of experimental summer drought. The fate of C$_{new}$ to growth and CO$_{2}$ efflux was tracked along branches, stems, coarse- and fine roots, ectomycorrhizae and root exudates to soil CO$_{2}$ efflux after drought release. Compared with control trees, drought recovering trees showed an overall 6% lower C sink activity and 19% less allocation of C$_{new}$ to aboveground sinks, indicating a low priority for aboveground sinks during recovery. In contrast, fine-root growth in recovering trees was seven times greater than that of controls. However, only half of the C used for new fine-root growth was comprised of C$_{new}$ while the other half was supplied by stored C. For drought recovery of mature spruce trees, in addition to C$_{new}$, stored C appears to be critical for the regeneration of the fine-root system and the associated water uptake capacity

Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values and small sample sizes.

The data set supporting the results of this article is available in the Dryad repository, http://dx.doi.org/10.5061/dryad.6f4qs. Moustakas, A. and Evans, M. R. (2015) Effects of growth rate, size, and light availability on tree survival across life stages: a demographic analysis accounting for missing values.Plant survival is a key factor in forest dynamics and survival probabilities often vary across life stages. Studies specifically aimed at assessing tree survival are unusual and so data initially designed for other purposes often need to be used; such data are more likely to contain errors than data collected for this specific purpose

Combating the effects of climatic change on forests by mitigation strategies

<p>Abstract</p> <p>Background</p> <p>Forests occur across diverse biomes, each of which shows a specific composition of plant communities associated with the particular climate regimes. Predicted future climate change will have impacts on the vulnerability and productivity of forests; in some regions higher temperatures will extend the growing season and thus improve forest productivity, while changed annual precipitation patterns may show disadvantageous effects in areas, where water availability is restricted. While adaptation of forests to predicted future climate scenarios has been intensively studied, less attention was paid to mitigation strategies such as the introduction of tree species well adapted to changing environmental conditions.</p> <p>Results</p> <p>We simulated the development of managed forest ecosystems in Germany for the time period between 2000 and 2100 under different forest management regimes and climate change scenarios. The management regimes reflect different rotation periods, harvesting intensities and species selection for reforestations. The climate change scenarios were taken from the IPCC's Special Report on Emission Scenarios (SRES). We used the scenarios A1B (rapid and successful economic development) and B1 (high level of environmental and social consciousness combined with a globally coherent approach to a more sustainable development). Our results indicate that the effects of different climate change scenarios on the future productivity and species composition of German forests are minor compared to the effects of forest management.</p> <p>Conclusions</p> <p>The inherent natural adaptive capacity of forest ecosystems to changing environmental conditions is limited by the long life time of trees. Planting of adapted species and forest management will reduce the impact of predicted future climate change on forests.</p

Reconciling global-model estimates and country reporting of anthropogenic forest CO2 sinks

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordData availability: The data that support the findings of this study are available from the corresponding author upon request.Achieving the long-term temperature goal of the Paris Agreement requires forest-based mitigation. Collective progress towards this goal will be assessed by the Paris Agreement’s Global stocktake. At present, there is a discrepancy of about 4 GtCO2yr−1in global anthropogenic net land-use emissions between global models (reflected in IPCC assessment reports) and aggregated national GHG inventories (under the UNFCCC). We show that a substantial part of this discrepancy (about 3.2 GtCO2yr−1) can be explained by conceptual differences in anthropogenic forest sink estimation, related to the representation of environmental change impacts and the areas considered as managed. For a more credible tracking of collective progress under the Global stocktake, these conceptual differences between models and inventories need to be reconciled. We implement a new method of disaggregation of global land model results that allows greater comparability with GHG inventories. This provides a deeper understanding of model–inventory differences, allowing more transparent analysis of forest-based mitigation and facilitating a more accurate Global stocktake.J.H. was supported by EU FP7 through project LUC4C (GA603542) and the UK NERC project GGRiLS-GAP. G.G. was supported by Administrative Arrangement Number 340203/2016/742550/SER/CLIMA.A3. A.K.J. was supported by the NSF (AGS 12-43071) and DOE (DE-SC0016323). J.E.M.S.N. was supported by the German Research Foundation’s Emmy Noether Programme (grant number PO1751/1-1). G.G., J.H., G.P.P. and L.P. received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 776810 (VERIFY). C.D.K. was supported by the US DOE under Contract DE-AC02-05CH11231 as part of their RGMA (BGC-Feedbacks SFA) and TES Programs (NGEE-Tropics). A.K.J. was supported under the US NSF (NSF-AGS-12-43071)

Forest carbon sequestration:the impact of forest management

In this chapter, we describe alternative ways in which forests and forestry can help to mítigate climate change, along with the potential impact of these activities. The three carbon storage compartments should be considered inall impact estimates. Carbon content in living biomass is easily estimated via species-specific equations or by applying factors to oven-dry biomass weights (e.g.,lbañez et al.,2002, Herrero et al.,2011,Castaño and Bravo, 2012).Litter carbon content has been analysed in many studies on primary forest productivity, though information regarding the influence of forest management on litter carbon content is less abundant (Blanco et al., 2006). In the last decade,efforts have been made to assess soil carbon in forests, but studies on the effect of forest management on soils show discrepancies (Lindner and Karjalainen,2007).Hoover (2011), for example,found no difference in forest floor carbon stocks among stands subjected to partial or complete harvest treatments in the United States.Instituto Universitario de Gestión Forestal Sostenibl