Gastric cancer (GC) is the third cause of cancer-related death worldwide. Patients with unresectable GC can be treated with chemotherapy such as paclitaxel, which is a microtubule stabilizer. The use ...of nanoparticle albumin-bound paclitaxel (nab-ptx) avoids hypersensitivity reactions due to the absence of solvent needed to dissolve paclitaxel and it can be administered at higher doses. The ABSOLUTE randomized phase-3 clinical trial showed the non-inferiority of the nab-ptx used every week compared to the solvent-based paclitaxel used every week. This review describes the current advancements of the use of nab-ptx in GC in preclinical and clinical study investigations. The possibility of combining nab-ptx with other medications to improve response of patients to their specific molecular needs will also be debated.
Ozone concentrations in excess of health‐based standards occur along the coastline of Lake Michigan. A complex pattern of ozone precursor emissions interfaces with a complex meteorological ...environment, presenting a challenge for air quality management and simulation. Precursors are transported into a shallow, stable boundary layer over the lake. This is followed by ozone formation and transport back onshore through a combination of synoptic and lake breeze winds. In this study, we use measurements during the Lake Michigan Ozone Study 2017 (LMOS) to quantitatively evaluate the Weather Research and Forecasting with Chemistry (WRF‐Chem) model at 4 km horizontal resolution for key features of high ozone episodes over Southern Lake Michigan, with a focus on meteorological performance. WRF‐Chem showed good performance and successful reproduction of meteorological fields and clouds. Lake breeze model skill was inconsistent, with both good and poor performance depending on site and day. The combination of Noah land surface model and High‐Resolution Rapid Refresh meteorology gave the best performance with the mean bias of −0.5 °C for temperature, −0.6 °C for dewpoint temperature, and −0.3 m/s for wind speed along the western coast of Lake Michigan during the daytime. For ozone, WRF‐Chem was biased low (−4.4 ppb mean bias for daytime ozone) and underestimated hourly peak ozone. In some cases, ozone bias can be attributed to transport and lake breeze errors. Average ozone concentration showed minor (<2 ppb) sensitivity to changes to meteorology initial and boundary conditions or the land surface model.
Key Points
WRF‐Chem achieved good meteorological performance around Lake Michigan, with acceptable reproduction of clouds, but inconsistencies for lake breeze
Campaign‐specific meteorological measurements by aircraft and ground‐based remote sensing provide a unique test of model skill
The 3‐km High‐Resolution Rapid Refresh (HRRR) model is a useful tool for initial and boundary conditions for the air quality community
Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still ...represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.
Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour ...infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: “0” or absent (between 0 and 5%), “1” or low (between 6 and 25%), “2” or moderate (between 26 and 50%) and “3” or high (between 51 and 75%). OS was then correlated with different TILs’ expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92–3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80–3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors’ efficacy warrants future investigation.
Particulate matter (PM) mass concentrations, seasonal cycles, source sector, and source region contributions in Central Asia (CA) are analyzed for the period April 2008-July 2009 using the Sulfur ...Transport and dEposition Model (STEM) chemical transport model and modeled meteorology from the Weather Research and Forecasting (WRF) model. Predicted aerosol optical depth (AOD) values (annual mean value similar to 0.2) in CA vary seasonally, with lowest values in the winter. Surface PM2.5 concentrations (annual mean value similar to 10 mu g m-3) also exhibit a seasonal cycle, with peak values and largest variability in the spring/summer, and lowest values and variability in the winter (hourly values from 2 to 90 mu g m-3). Surface concentrations of black carbon (BC) (mean value similar to 0.1 mu g m-3) show peak values in the winter. The simulated values are compared to surface measurements of AOD as well as PM2.5, PM10, BC, and organic carbon (OC) mass concentrations at two regional sites in Kyrgyzstan (Lidar Station Teplokluchenka (LST) and Bishkek). The predicted values of AOD and PM mass concentrations and their seasonal cycles are fairly well captured. The carbonaceous aerosols are underpredicted in winter, and analysis suggests that the winter heating emissions are underestimated in the current inventory. Dust, from sources within and outside CA, is a significant component of the PM mass and drives the seasonal cycles of PM and AOD. On an annual basis, the power and industrial sectors are found to be the most important contributors to the anthropogenic portion of PM2.5. Residential combustion and transportation are shown to be the most important sectors for BC. Biomass burning within and outside the region also contributes to elevated PM and BC concentrations. The analysis of the transport pathways and the variations in particulate matter mass and composition in CA demonstrates that this region is strategically located to characterize regional and intercontinental transport of pollutants. Aerosols at these sites are shown to reflect dust, biomass burning, and anthropogenic sources from Europe; South, East, and Central Asia; and Russia depending on the time period. Simulations for a reference 2030 emission scenario based on pollution abatement measures already committed to in current legislation show that PM2.5 and BC concentrations in the region increase, with BC growing more than PM2.5 on a relative basis. This suggests that both the health impacts and the climate warming associated with these particles may increase over the next decades unless additional control measures are taken. The importance of observations in CA to help characterize the changes that are rapidly taking place in the region are discussed.
The impacts of black carbon (BC) and particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) emissions from different source sectors (e.g., transportation, power, industry, ...residential, and biomass burning) and geographic source regions (e.g., Europe, North America, China, Russia, central Asia, south Asia, and the Middle East) to Arctic BC and PM2.5 concentrations are investigated through a series of annual sensitivity simulations using the Weather Research and Forecasting – sulfur transport and deposition model (WRF-STEM) modeling framework. The simulations are validated using observations at two Arctic sites (Alert and Barrow Atmospheric Baseline Observatory), the Interagency Monitoring of Protected Visual Environments (IMPROVE) surface sites over the US, and aircraft observations over the Arctic during spring and summer 2008. Emissions from power, industrial, and biomass burning sectors are found to be the main contributors to the Arctic PM2.5 surface concentration, with contributions of ∼ 30 %, ∼ 25 %, and ∼ 20 %, respectively. In contrast, the residential and transportation sectors are identified as the major contributors to Arctic BC, with contributions of∼ 38 % and ∼ 30 %. Anthropogenic emissions are the most dominant contributors (∼ 88 %) to the BC surface concentration over the Arctic annually; however, the contribution from biomass burning is significant over the summer (up to ∼ 50 %). Among all geographical regions, Europe and China have the highest contributions to the BC surface concentrations, with contributions of ∼ 46 % and ∼ 25 %, respectively. Industrial and power emissions had the highest contributions to the Arctic sulfate (SO4) surface concentration, with annual contributions of ∼ 43 % and ∼ 41 %, respectively. Further sensitivity runs show that, among various economic sectors of all geographic regions, European and Chinese residential sectors contribute to∼ 25 % and ∼ 14 % of the Arctic average surface BC concentration. Emissions from the Chinese industry sector and European power sector contribute ∼ 12 % and ∼ 18 % of the Arctic surface sulfate concentration. For Arctic PM2.5, the anthropogenic emissions contribute > ∼ 75 % at the surface annually, with contributions of ∼ 25 % from Europe and ∼ 20 % from China; however, the contributions of biomass burning emissions are significant in particular during spring and summer. The contributions of each geographical region to the Arctic PM2.5 and BC vary significantly with altitude. The simulations show that the BC from China is transported to the Arctic in the midtroposphere, while BC from European emission sources are transported near the surface under 5 km, especially during winter.
Breast cancer (BC) is the second most common cause of cancer‐related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit ...patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3‐kinase (PI3K) enzymes are involved in numerous cellular‐ functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20‐40% of BC. We performed a meta‐analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor, and predictor of response to anti‐cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR = 1.67, 95%CI: 1.15‐2.43; P = 0.007) in BC, as previously reported. As PI3K signaling is also a result of other pathways’ hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti‐PI3K/mTOR, anti‐HER2, and other TKRs is warranted in future randomized clinical trials.
Breast cancer is the second most common cause of cancer‐related deaths in women. More accurate biomarkers of response to treatment and predictors of prognosis are needed. Phosphatidylinositol 3‐kinase gene is mutated in 20‐40% of BC. In our meta‐analysis PI3K is an independent negative prognostic factor and correlates with a worse prognosis (P = 0.007)
In this meta‐analysis investigating the role of PIK3CA mutations in 1928 breast cancer cases, it was proved that the mutational status of this gene was an independent negative prognostic factor, and correlated with a worse prognosis (HR = 1.67, 95%CI: 1.15‐2.43; P = 0.007).
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