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1.
Sci Rep ; 13(1): 15825, 2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37739968

RESUMEN

Two field trials (2017 and 2018) evaluated the performance of barley-pea mixed cropping by comparing different sowing densities (replacement design) and tailoring N fertilization on barley sowing density (split-plot design). High and Low N inputs were applied to whole plots whereas barley and pea, as pure and in mixed crops, were applied to subplots. The 2017 trial suggested the occurrence of an interaction between soil physical properties and N fertilization. Therefore, in 2018 a pedological survey allowed the soil effect to be included in the ANOVA model applied to evaluate crop performance parameters, showing that N fertilization positively affected barley performance only in the soil unit located downslope. A significantly lower presence of weeds was observed in mixed crops rather than in pea pure crops. Overall, increasing pea density and reducing barley density in mixed crops, and tailoring N fertilization were effective approaches to obtain a more balanced mixed grain at harvest. The combination of crop performance evaluation and assessments of soil conditions suggested that more sustainable agricultural systems, based on mixed cropping and a significant reduction of N fertilizers and herbicides, can be achieved with barley-pea mixed cropping as an alternative to pure cropping systems.


Asunto(s)
Hordeum , Suelo , Pisum sativum , Reimplantación , Productos Agrícolas , Fertilización
2.
J Environ Manage ; 330: 117181, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36623390

RESUMEN

In forest ecosystems, soil-plant interactions drive the physical, chemical, and biological soil properties and, through soil organic matter cycling, control the dynamics of nutrient cycles. Parent material also plays a fundamental role in determining soil's chemical properties and nutrient availability. In this study, eight long-time coppice-managed Holm oak forests under conversion to high forest, located under similar climatic conditions in Tuscany and Sardinia Regions (Italy), and grown on soils developed from three different lithologies (limestone, biotite granite, and granite with quartz veins) were evaluated. The research aimed to a) estimate the amount of C and nutrients (total N and potentially available P, Ca, Mg, and K) stored both in the organic, organo-mineral, and mineral horizons and at fixed depth intervals (0-0.3 and 0.3-0.5 m), and b) assess the dominant pedological variables driving elemental accumulation. The soils were described and sampled by genetic horizons and each sample was analyzed for its C and nutrient concentration in both the fine earth and skeleton fractions. Despite the different parent materials from which the soils had evolved, the physicochemical properties and the C and nutrient stocks for the 0-0.3 and 0.3-0.5 m layers did not show substantial differences among the eight soils. Conversely, some differences were observed in the stocks of potentially available P and Ca per 0.01 m of mineral horizons. The findings show that over time, plant-induced pedogenic processes (acidification, mineral weathering, organic matter addition, and nutrient cycling) almost obliterated the influence of parent materials on soil properties. This resulted in the upper soil horizons that showed similar characteristics, even though derived from different lithologies. However, among the study sites, some differences occurred due to lithology, as in the case of the soils derived from calcareous parent materials that had high concentrations of exchangeable Ca in the mineral horizons and, likely, to environmental variables (e.g., exposure), which possibly influenced litter degradation and the release of nutrients such as N and available P.


Asunto(s)
Quercus , Suelo , Suelo/química , Ecosistema , Bosques , Minerales , Árboles
3.
J Environ Manage ; 322: 116031, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36055093

RESUMEN

Slash and burn is a land use practice widespread all over the world, and nowadays it is formally recognized as the principal livelihood system in rural areas of South America, Asia, and Africa. The practice consists of a land rotation where users cut native or secondary forest to establish a new crop field and, in some cases, build charcoal kilns with the cut wood to produce charcoal. Due to several socio-economic changes in developing countries, some scientists and international organizations have questioned the sustainability of slash and burn since in some cases, crop yield does not justify the soil degradation caused. To estimate the soil quality in agricultural and forest soils at different ages of the forest-fallow period (25, 35, and 50 years), this survey investigated rural areas in three locations in Manica province, central Mozambique: Vanduzi, Sussundenga, and Macate. Soil profiles were trenched and sampled with a pedological approach under crop fields and forest-fallow. The chronosequence was selected to test the hypothesis that the increase in forest-fallow age causes an improvement of soil fertility. Results highlighted discrete variations among locations in mineralogy, Al- and Fe-oxyhydroxides, sand, silt, pH, total organic carbon, humic carbon, total nitrogen, available phosphorous, chloride, nitrate, fluoride, and ammonium. Few differences in mineralogy, Fe-oxyhydroxides, available P, chloride, and nitrate were detected between crop fields and forest-fallow within the same location. Such differences were mostly ascribed to intrinsic fertility inherited from the parent material rather than a longer forest-fallow period. However, physicochemical soil property improvement did not occur under a forest age of 50 years (the longest forest-fallow considered), indicating that harmonization of intrinsic fertility and agronomic practices may increase soil organic matter and nutrient contents more than a long forest-fallow period.


Asunto(s)
Compuestos de Amonio , Quemaduras , Agricultura/métodos , Carbono , Carbón Orgánico , Cloruros , Fluoruros , Humanos , Persona de Mediana Edad , Mozambique , Nitratos , Nitrógeno , Compuestos de Fósforo , Arena , Suelo/química
4.
J Transl Med ; 20(1): 290, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-35761360

RESUMEN

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy. METHODS: The induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice. RESULTS: Our results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy. CONCLUSION: These data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.


Asunto(s)
Cloroquina , Resistencia a Antineoplásicos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Neoplasias de la Mama Triple Negativas , Animales , Autofagia , Línea Celular Tumoral , Proliferación Celular , Cloroquina/farmacología , Cloroquina/uso terapéutico , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico
5.
J Environ Manage ; 312: 114935, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35378467

RESUMEN

In forest ecosystems, a variety of abiotic and biotic soil forming factors drives soil organic matter (SOM) and nutrients cycling with a profitable outcome on climate change mitigation. As a consequence, type and intensity of forest management, through its impact on carbon (C) and nutrient soil stocks, can be considered as an additional soil forming force. In this study, we investigated the influence of the coppice conversion into high forest on pedogenesis and on soil C and nutrient (N, P, Ca, Mg, and K) stocks, fifty years later the beginning of the conversion-cycle. The trial was established in a Turkey oak forest historically managed under the coppice system in central Italy. Specifically, we considered tree population density (natural evolution - control, moderate thinning, heavy thinning) where soil samples were collected according to genetic horizon to estimate C, N, and P stocks both in the forest floor and at fixed depth intervals (0-30, 30-50 and 50-75 cm). Further, the stocks of exchangeable Ca, Mg, and K were also assessed for the mineral layers. The results showed that litter and the upper layer of mineral soil (0-30 cm) contained a similar quantity of C (about 74-83 Mg ha-1), independently of the trials and no differences were observed also in the whole soil stocks (about 192-213 Mg ha-1). The comparison of the mean stocks calculated per 1-cm of thickness of organic (O), organo-mineral (OM), and mineral (M) layers, although it did not display any difference among trials (excepted for P and Mg), showed a similar capability of the organo-mineral horizons to store C and nutrients compared with the organic ones (e.g., about 6-12 Mg ha-1, 0.3-0.5 Mg ha-1 and 0.5-1.5 kg ha-1 for C, N and P, respectively). Our findings showed that thinning operated on Turkey oak coppice did not affect soil capacity to store C and nutrients. These results suggested that the forest ecosystem itself is the main soil forming force and this is consistent with the target of adopting forest management able to control the global C cycle through the storage of SOM in the mineral soil rather than in forest floor, where SOM turnover is faster.


Asunto(s)
Quercus , Suelo , Carbono/análisis , Ecosistema , Bosques , Italia , Minerales , Nutrientes
6.
Environ Geochem Health ; 44(10): 3425-3449, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34617246

RESUMEN

Urban soils are often mixed with extraneous materials and show a high spatial variability that determine great differences from their agricultural or natural counterparts. The soils of 18 localities of a medium-sized city (Ancona, Italy) were analysed for their main physicochemical and biological properties, and for chromium (Cr), copper (Cu), cobalt (Co), lead (Pb), nickel (Ni), zinc (Zn), and mercury (Hg) total content, distribution among particle-size fractions, and extractability. Because of the absence of thresholds defining a hot spot for heavy metal pollution in urban soils, we defined a "threshold of attention" (ToA) for each heavy metal aiming to bring out hot spot soils where it is more impellent to intervene to mitigate or avoid potential environmental concerns. In several city locations, the soil displayed sub-alkaline pH, large contents of clay-size particles, and higher TOC, total N, and available P with respect to the surrounding rural areas, joined with high contents of total heavy metals, but low availability. The C biomass, basal respiration, qCO2, and enzyme activities were compared to that detected in the near rural soils, and results suggested that heavy metals content has not substantially compromised the soil ecological services. We conclude that ToA can be considered as a valuable tool to highlight soil hot spots especially for cities with a long material history and, for a proper risk assessment in urban soils, we suggest considering the content of available heavy metals (rather than the total content) and soil functions.


Asunto(s)
Mercurio , Metales Pesados , Contaminantes del Suelo , China , Cromo/análisis , Ciudades , Arcilla , Cobalto/análisis , Cobre/análisis , Monitoreo del Ambiente , Plomo/análisis , Mercurio/análisis , Metales Pesados/análisis , Níquel/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisis , Zinc/análisis
7.
Bioresour Technol ; 340: 125662, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34333345

RESUMEN

Post-digestate treatments may reduce the risk linked to Antibiotic Resistant Genes (ARGs) release with digestate direct land application. Thus, this study aimed to evaluate post-digestate composting and co-composting with biogas production feedstock (maize silage, food processing waste, and poultry litter) effect on abundance of selected ARGs: erm(B), tet(K), tet(M), tet(O), and tet(S) genes. More than 80% of all ARGs were removed after 90 days of composting but removals from co-composting were lower. Bacteroidetes, Firmicutes, and Proteobacteria dominated fresh digestate, and a network analysis indicated that these were potential hosts of ARGs. The emergence of Actinobacteria (dominant), Planctomycetes, and Verrucomicrobia phyla during composting shifted the microbial composition. Moreover, canonical correspondence analysis showed trace elements explaining 90% variations in ARGs abundance. The study illustrates significance of post-digestate composting in mitigating ARGs release, and effectiveness could be linked to shift in microbial composition and trace elements release.


Asunto(s)
Compostaje , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Genes Bacterianos , Estiércol
8.
Bioresour Technol ; 338: 125550, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34274591

RESUMEN

The current study evaluated the quality of agricultural waste digestate by composting or co-composting with biogas feedstock (maize silage, food processing waste, or poultry litter). Temperature, phytotoxicity, C/N ratio, water extractable trace elements, and 14 enzyme activities were monitored. Temperature dropped earlier in digestate and maize silage co-composting pile, reducing time to maturity by 20 days. Composting and co-composting reduced phytotoxicity and C/N ratio, but increased immobilization of Al, Ba, Fe, Zn, and Mn at least by 40% in all piles. All the enzyme activities, except arylsulfatase and α-glucosidase, increased at the maturity phase and negatively correlated with organic matter content and most of trace elements. Post-digestate composting or co-composting with biogas feedstock is a promising strategy to improve digestate quality for fertilizer use, and selected enzyme activities can be indicators of compost maturity and immobilization of trace elements.


Asunto(s)
Compostaje , Oligoelementos , Fertilizantes/análisis , Ensilaje , Suelo
9.
Pharmaceutics ; 13(5)2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-34068626

RESUMEN

BACKGROUND: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. METHODS: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. RESULTS AND CONCLUSIONS: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time.

10.
Environ Res ; 197: 111011, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33774017

RESUMEN

Cattle manure and poultry litter are widely used as fertilizers as they are excellent sources of nutrients; however, potential adverse environmental effects exist during land applications, due to the release of zoonotic bacteria and antimicrobial resistance (AMR) genes. This study was conducted to understand linkages between physiochemical composition, bacterial diversity, and AMR gene presence of cattle manure and poultry litter using quantitative polymerase chain reaction to enumerate four AMR genes (ermB, sulI, intlI, and blactx-m-32), Illumina sequencing of the 16 S region, and analysis of physical and chemical properties. Principal coordinate analysis of Bray-Curtis distance revealed distinct bacterial community structures between the two manure sources. Greater alpha diversity occurred in cattle manure compared to poultry litter (P < 0.05). Redundancy analysis showed a strong relationship between manure physiochemical and composition and bacterial abundance, with positive relationships occurring among electrical conductivity and carbon/nitrogen, and negative associations for total solids and soluble fractions of heavy metals. Cattle manure exhibited greater abundance of macrolide (ermB) and sulfonamide (sulI) resistant genes. Consequently, fresh cattle manure applications may result in greater potential spread of AMR genes to the soil-water environment (relative to poultry litter) and novel best management strategies (such as composting) may reduce the release of AMR genes to the soil-water environment.


Asunto(s)
Antibacterianos , Estiércol , Animales , Antibacterianos/farmacología , Bovinos , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Aves de Corral , Suelo
11.
J Clin Med ; 10(1)2021 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-33401546

RESUMEN

Several studies have highlighted the key role of chronic inflammation in breast cancer development, progression, metastasis, and therapeutic outcome. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Recent findings suggest that positive psychosocial experiences, including psychotherapeutic interventions and therapeutic mind-body protocols, can modulate the inflammatory response by reducing the expression of genes/proteins associated with inflammation and stress-related pathways. Our preliminary results indicate that a specific mind-body therapy (MBT-T) could induce a significant reduction of the release of different cytokines and chemokines, such as SCGFß, SDF-1α, MCP3, GROα, LIF, and IL-18, in the sera of breast cancer patients compared to a control group, suggesting that MBT-T could represent a promising approach to improve the wellness and outcome of breast cancer patients.

12.
Int J Mol Sci ; 21(21)2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33105796

RESUMEN

Breast cancer is a heterogeneous disease consisting of different biological subtypes, with differences in terms of incidence, response to diverse treatments, risk of disease progression, and sites of metastases. In the last years, several molecular targets have emerged and new drugs, targeting PI3K/Akt/mTOR and cyclinD/CDK/pRb pathways and tumor microenvironment have been integrated into clinical practice. However, it is clear now that breast cancer is able to develop resistance to these drugs and the identification of the underlying molecular mechanisms is paramount to drive further drug development. Autophagy is a highly conserved homeostatic process that can be activated in response to antineoplastic agents as a cytoprotective mechanism. Inhibition of autophagy could enhance tumor cell death by diverse anti-cancer therapies, representing an attractive approach to control mechanisms of drug resistance. In this manuscript, we present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Antineoplásicos/uso terapéutico , Autofagia/fisiología , Neoplasias de la Mama/metabolismo , Ensayos Clínicos como Asunto , Femenino , Humanos , Terapia Molecular Dirigida/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral
13.
Int J Mol Sci ; 21(20)2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33096896

RESUMEN

Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.


Asunto(s)
Biomarcadores Farmacológicos/metabolismo , Cardiotoxicidad/etiología , Ipilimumab/efectos adversos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Compuestos de Bencidrilo/farmacología , Antígeno CTLA-4/metabolismo , Cardiotoxicidad/metabolismo , Línea Celular Tumoral , Femenino , Glucosa/metabolismo , Glucosa/farmacología , Glucósidos/farmacología , Humanos , Hiperglucemia/etiología , Leucotrieno B4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Factor de Transcripción ReIA/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología
14.
Int J Mol Sci ; 21(17)2020 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-32899139

RESUMEN

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients' characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67-0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]).


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/mortalidad , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Femenino , Humanos , Metástasis de la Neoplasia , Pronóstico , Tasa de Supervivencia
15.
Int J Mol Sci ; 21(18)2020 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899866

RESUMEN

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.


Asunto(s)
Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Piperazinas/farmacología , Purinas/farmacología , Piridinas/farmacología , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo
16.
Int J Mol Sci ; 21(13)2020 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-32605126

RESUMEN

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by aggressive behavior, high risk of distant recurrence, and poor survival. Chemotherapy is still the main therapeutic approach for this subgroup of patients, therefore, progress in the treatment of TNBC remains an important challenge. Data derived from molecular technologies have identified TNBCs with different gene expression and mutation profiles that may help developing targeted therapies. So far, however, only a few of these have shown to improve the prognosis and outcomes of TNBC patients. Robust predictive biomarkers to accelerate clinical progress are needed. Herein, we review prognostic and predictive biomarkers in TNBC, discuss the current evidence supporting their use, and look at the future of this research field.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Regulación Neoplásica de la Expresión Génica , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Pronóstico
17.
Sci Total Environ ; 721: 137532, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32179343

RESUMEN

This review was aimed to summarize and critically evaluate studies on removal of veterinary antibiotics (VAs), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) with anaerobic digestion (AD) of manure and demonstrate areas of focus for improved removal efficiency. The environmental risks associated to the release of the same were also critically evaluated. The potential of AD and advanced AD of manure on removal rate of VAs, ARGs and MGEs was thoroughly assessed. In addition, the role of post and pre-AD treatments and their potential to support VAs and ARGs removal efficiency were evaluated. The overall review results show disparity among the different groups of VAs in terms of removal rate with relatively higher efficiency for ß-lactams and tetracyclines compared to the other groups. Some of sulfonamides, fluoroquinolones and macrolides were reported to be highly persistent with removal rates as low as zero. Within group differences were also reported in many literatures. Moreover, removal of ARGs and MGEs by AD was widely reported although complete removal was hardly possible. Even in rare scenarios, some AD conditions were reported to increase copies of specific groups of the genes. Temperature pretreatments and temperature phased advanced AD were also reported to improve removal efficiency of VAs while contributing to increased biogas production. Moreover, a few studies also showed the possibility of further removal by post-AD treatments such as liquid-solid separation, drying and composting. In conclusion, the various studies revealed that AD in its current technological level is not a guarantee for complete removal of VAs, ARGs and MGEs from manure. Consequently, their possible release to the soils with digestate could threaten the healthcare and disturb soil microbial ecology. Thus, intensive management strategies need to be designed to increase removal efficiency at the different manure management points along the anaerobic digestion process.


Asunto(s)
Antibacterianos/farmacología , Estiércol , Anaerobiosis , Farmacorresistencia Microbiana/efectos de los fármacos , Genes Bacterianos/efectos de los fármacos
18.
Mol Biosyst ; 13(12): 2687-2696, 2017 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-29072741

RESUMEN

Endocrine disrupting chemicals (EDCs) are natural or synthetic exogenous substances affecting human health. Although present at low concentrations in the environment, they can cause a broad range of negative effects on the endocrine functions by mimicking the action of steroid hormones due to their structural similarity. Hormonal unbalance can play an important role in carcinogenesis at any stage of disease. In the case of the breast cancer, EDCs directly affect the transformation of normal breast cells into cancer cells by interfering with hormonal regulation and by inducing the alteration of factors that regulate gene expression. The principal aims of this work were to study the interaction networks of proteins modulated in breast cancer by either environmental EDCs or mycotoxins, and to identify the proteins with the strongest coordination role defined as hub nodes. Our studies evidenced the presence of seven and six hub proteins in two EDCs and mycotoxins networks, respectively. Then, by merging the two networks, we identified that three hub nodes (BCL2, ESR2 and CTNNB1) in the environmental EDCs network show direct interactions with three hub nodes (CASP8, RELA and MKI67) in the mycotoxins network. These data highlighted that two networks are linked through proteins involved in the apoptosis regulation and in processes related to cell proliferation and survival, and, thus, in breast cancer progression.


Asunto(s)
Neoplasias de la Mama/etiología , Disruptores Endocrinos/toxicidad , Neoplasias de la Mama/metabolismo , Caspasa 8/metabolismo , Femenino , Humanos , Micotoxinas/metabolismo , Factor de Transcripción ReIA/metabolismo
19.
Pharmacol Res ; 103: 56-68, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26484591

RESUMEN

The mitochondrial ATPase Inhibitory Factor 1 (hereafter referred to as IF1) blocks the reversal of the F1Fo-ATPsynthase to prevent detrimental consumption of cellular ATP and associated demise. Herein, we infer further its molecular physiology by assessing its protective function in neurons during conditions of challenged homeostatic respiration. By adopting in vitro and in vivo protocols of hypoxia/ischemia and re-oxygenation, we show that a shift in the IF1:F1Fo-ATPsynthase expression ratio occurs in neurons. This increased IF1 level is essential to induce accumulation of the PTEN-induced putative kinase 1 (PINK-1) and recruitment of the mitophagic ubiquitin ligase PARK-2 to promote autophagic "control" of the mitochondrial population. In IF1 overexpressing neurons ATP depletion is reduced during hypoxia/ischemia and the mitochondrial membrane potential (ΔYm) resilient to re-oxygenation as well as resistant to electrogenic, Ca(2+) dependent depolarization. These data suggest that in mammalian neurons mitochondria adapt to respiratory stress by upregulating IF1, which exerts a protective role by coordinating pro-survival cell mitophagy and bioenergetics resilience.


Asunto(s)
Hipoxia/metabolismo , Mitocondrias/metabolismo , Neuronas/metabolismo , Proteínas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Autofagia , Línea Celular Tumoral , Células Cultivadas , Corteza Cerebral/citología , Humanos , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Potencial de la Membrana Mitocondrial , Mitocondrias/fisiología , Ratas , Regulación hacia Arriba , Proteína Inhibidora ATPasa
20.
Ecol Evol ; 5(20): 4542-54, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26668721

RESUMEN

In alpine environments, colonies of snow vole (Chionomys nivalis Martins) cause strong pedoturbation, which may affect humification process and soil organic matter (SOM) cycling, with repercussions on the hormone-like activity of organics. We investigated the effect of snow vole pedoturbation on the chemical and spectroscopic features of soil organic fractions, and the potential hormone-like activity of humic and fulvic acids (HA, FA). The study site was located on the high-mountain environment of the Majella massif (central Italy). Pedoturbated and regular soils were morphologically described and characterized for pH and content of total organic carbon, total extractable carbon, HA, and FA. Both HA and FA were extracted and investigated using attenuated total reflectance/Fourier transform infrared (ATR/FTIR), nuclear magnetic resonance with high-resolution magic angle spinning (HRMAS-NMR), and (1)H-(13)C heteronuclear single quantum coherence (HSQC). HA and FA were also tested for their auxin-like and gibberellin-like activities. Results provide evidences that bioturbated and regular soils contain a poorly decomposed SOM, but HA and FA with a well-defined molecular structure. The HA and FA from both bioturbated and regular soils show a hormone-like activity with a different allocation along the soil profile. In the regular soil, the highest auxin-like activity was shown by HA and FA from Oe1 horizon, while gibberellin-like activity was expressed by FA from Oe2 horizon. Burrowing activity determines a redistribution of organics throughout the profile with a relatively high auxin-like activity in the FA from straw tunnel wall (STW) and gibberellin-like activity in the HA from vole feces (VF). The relative high presence of carboxylic acids, amides, proteins, and amino acids in the FA from STW and the aromatic moieties in the HA from VF put evidences for their different behavior. The fact that snow vole activity has modified the chemical and biological properties of SOM in these soils otherwise considered governed only by low temperature has important ecological implications such as the preservation of soil fertility and vegetal biodiversity.

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