30 research outputs found
Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity
Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, Ï = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, Ï = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations
Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study)
Background
Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment.
Methods
This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival.
Results
Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58â85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17).
Conclusions
The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival
The tundra phenology database: more than two decades of tundra phenology responses to climate change
Observations of changes in phenology have provided some of the strongest
signals of the effects of climate change on terrestrial ecosystems. The International
Tundra Experiment (ITEX), initiated in the early 1990s, established a common protocol to
measure plant phenology in tundra study areas across the globe. Today, this valuable collection
of phenology measurements depicts the responses of plants at the colder extremes of
our planet to experimental and ambient changes in temperature over the past decades.
The database contains 150 434 phenology observations of 278 plant species taken at 28 study
areas for periods of 1\u201326 years. Here we describe the full data set to increase the
visibility and use of these data in global analyses and to invite phenology data contributions
from underrepresented tundra locations. Portions of this tundra phenology database have
been used in three recent syntheses, some data sets are expanded, others are from entirely
new study areas, and the entirety of these data are now available at the Polar Data Catalogue
(https://doi.org/10.21963/13215)
Global maps of soil temperature
Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0â5 and 5â15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (â0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications
The tundra phenology database: More than two decades of tundra phenology responses to climate change
Observations of changes in phenology have provided some of the strongest signals of the effects of climate change on terrestrial ecosystems. The International Tundra Experiment (ITEX), initiated in the early 1990s, established a common protocol to measure plant phenology in tundra study areas across the globe. Today, this valuable collection of phenology measurements depicts the responses of plants at the colder extremes of our planet to experimental and ambient changes in temperature over the past decades. The database contains 150,434 phenology observations of 278 plant species taken at 28 study areas for periods of 1 to 26 years. Here we describe the full dataset to increase the visibility and use of these data in global analyses, and to invite phenology data contributions from underrepresented tundra locations. Portions of this tundra phenology database have been used in three recent syntheses, some datasets are expanded, others are from entirely new study areas, and the entirety of these data are now available at the Polar Data Catalogue (https://doi.org/10.21963/13215)
Global maps of soil temperature
Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0â5 and 5â15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (â0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications
Global maps of soil temperature
Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-kmÂČ resolution for 0â5 and 5â15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-kmÂČ pixels (summarized from 8500 unique temperature sensors) across all the worldâs major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications
Global maps of soil temperature.
Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications
LINFOCITI INFILTRANTI IL TUMORE, BAP-1, VEGFR-2 E IGF-1R NEL MESOTELIOMA PLEURICO MALIGNO
Scopo del Lavoro:
Il Mesotelioma Pleurico Maligno (MPM) Ăš un tumore raro correlato allâesposizione allâasbesto. MPM Ăš associato a una prominente reazione infiammatoria. In questo studio abbiamo valutato se ci fosse una relazione tra sopravvivenza e presenza di linfociti infiltranti il tumore (TILs). Nei campioni di mesotelioma Ăš stata anche analizzata lâespressione di BAP-1 (Proteina-1 associata a BRCA1), VEGFR-2 (recettore per il fattore di crescita endoteliale vascolare tipo-2) e IGF-1R (recettore per il fattore di crescita insulino-simile tipo-1).
Materiali e Metodi:
Sono stati considerati 42 casi di MPM. Tutti i campioni utilizzati sono stati ottenuti al momento della diagnosi. 24 erano di sesso maschile; lâetĂ media era 69 anni. I fumatori erano 26; i pazienti con una esposizione certa allâasbesto erano 26. Tutti i vetrini istologici sono stati revisionati: câerano 28 casi di sottotipo epitelioide, 8 casi di mesotelioma bifasico e 8 casi di sarcomatoide. La presenza di TILs Ăš stata descritta come assente, debole, moderata e forte mediante una valutazione quantitativa in ematossilina-eosina. Lâespressione di BAP-1, VEGFR-2, IGF-1R Ăš stata analizzata mediante immunoistochimica. Eâ stato inoltre esaminato lâimpatto sulla sopravvivenza dellâesposizione allâasbesto, del consumo di tabacco e dellâsottotipo istologico. Lâanalisi di sopravvivenza Ăš stata calcolata mediante la curva di Kaplan-Meyer.
Risultati:
I TILs erano presenti nellâ89% dei casi (espressione debole 18%, moderata 36%, forte 34%) ed erano un fattore prognostico favorevole (p=0.05). La sopravvivenza mediana dei pazienti con TILs e dei pazienti non-TILs era 21 mesi e 4 mesi, rispettivamente (Fig.1). Il sottotipo epitelioide di MPM era caratterizzato da unâaumentata espressione di VEGFR-2, sia nelle cellule tumorali (p=0.04) che nei TILs (p=0.05) e da una maggiore perdita di BAP1 (75%, p=0.05) rispetto al sottotipo bifasico e sarcomatoide. LâIGF-1R era overespresso nel 57% dei tumori (14 epitelioidi e 11 sarcomatoidi) e nel 23% dei TILs (7 epitelioidi e 3 sarcomatoidi). Lâespressione di VEGFR-2, BAP1 e IGF-1R non era significativamente correlata alla sopravvivenza. Il consumo di tabacco (p=0.93) e lâesposizione allâasbesto (p=0.62) non erano significativamente correlati alla sopravvivenza. Lâistologia non ha alcun effetto sulla sopravvivenza (p=0.23) sebbene il sottotipo epitelioide di MPM abbia un andamento migliore rispetto al sottotipo bifasico e sarcomatoide, la cui sopravvivenza mediana Ăš di 6 mesi.
Conclusioni:
La presenza di TILs influisce favorevolmente la sopravvivenza del MPM. Il sottotipo epitelioide Ăš caratterizzato da una maggiore sopravvivenza, una maggiore perdita di BAP1 e unâaumentata espressione di VEGFR-2. I marcatori istologici potrebbero migliorare la valutazione prognostica del MPM e fornire indicazioni importanti per nuove strategie terapeutiche